Sample records for understanding remains limited

  1. 22 CFR 1104.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... providing scientific or humanistic understandings of past human behavior, cultural adaptation, and related... but not limited to, vegetable and animal remains, coprolites); (vi) Human remains (including, but not...

  2. 36 CFR 296.3 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... providing scientific or humanistic understandings of past human behavior, cultural adaptation, and related..., but not limited to, vegetal and animal remains, coprolites); (vi) Human remains (including, but not...

  3. 36 CFR 296.3 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... providing scientific or humanistic understandings of past human behavior, cultural adaptation, and related..., but not limited to, vegetal and animal remains, coprolites); (vi) Human remains (including, but not...

  4. 22 CFR 1104.2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... providing scientific or humanistic understandings of past human behavior, cultural adaptation, and related... but not limited to, vegetable and animal remains, coprolites); (vi) Human remains (including, but not...

  5. 36 CFR 296.3 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... providing scientific or humanistic understandings of past human behavior, cultural adaptation, and related..., but not limited to, vegetal and animal remains, coprolites); (vi) Human remains (including, but not...

  6. Pre-Service Primary Teachers' Knowledge and Understanding of Geography and Its Teaching: A Review

    ERIC Educational Resources Information Center

    Catling, Simon

    2014-01-01

    It is a decade since the last review of the geographical understandings of pre-service primary teachers. Examining the range of research about novice primary teachers' geographical and environmental knowledge and understanding, it is clear there have been limited follow up studies, and there remain important gaps in the research. Research relevant…

  7. 32 CFR 229.3 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... capable of providing scientific or humanistic understandings of past human behavior, cultural adaptation... materials; (v) Organic waste (including, but not limited to, vegetal and animal remains, coprolites); (vi...

  8. 32 CFR 229.3 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... capable of providing scientific or humanistic understandings of past human behavior, cultural adaptation... materials; (v) Organic waste (including, but not limited to, vegetal and animal remains, coprolites); (vi...

  9. 32 CFR 229.3 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... capable of providing scientific or humanistic understandings of past human behavior, cultural adaptation... materials; (v) Organic waste (including, but not limited to, vegetal and animal remains, coprolites); (vi...

  10. Limitations in predicting the space radiation health risk for exploration astronauts.

    PubMed

    Chancellor, Jeffery C; Blue, Rebecca S; Cengel, Keith A; Auñón-Chancellor, Serena M; Rubins, Kathleen H; Katzgraber, Helmut G; Kennedy, Ann R

    2018-01-01

    Despite years of research, understanding of the space radiation environment and the risk it poses to long-duration astronauts remains limited. There is a disparity between research results and observed empirical effects seen in human astronaut crews, likely due to the numerous factors that limit terrestrial simulation of the complex space environment and extrapolation of human clinical consequences from varied animal models. Given the intended future of human spaceflight, with efforts now to rapidly expand capabilities for human missions to the moon and Mars, there is a pressing need to improve upon the understanding of the space radiation risk, predict likely clinical outcomes of interplanetary radiation exposure, and develop appropriate and effective mitigation strategies for future missions. To achieve this goal, the space radiation and aerospace community must recognize the historical limitations of radiation research and how such limitations could be addressed in future research endeavors. We have sought to highlight the numerous factors that limit understanding of the risk of space radiation for human crews and to identify ways in which these limitations could be addressed for improved understanding and appropriate risk posture regarding future human spaceflight.

  11. Educational Knowledge Brokerage and Mobilization: The "Marshall Memo" Case

    ERIC Educational Resources Information Center

    Malin, Joel R.; Paralkar, Vijay Keshaorao

    2017-01-01

    The importance of intermediation between communities primarily engaged in research production and those primarily engaged in practice is increasingly acknowledged, yet our understanding of the nature and influence of this work in education remains limited. Accordingly, this study utilizes case study methodology and aspires to understand the…

  12. Ecological economics and institutional change.

    PubMed

    Krall, Lisi; Klitgaard, Kent

    2011-02-01

    Ecological economics remains unfinished in its effort to provide a framework for transforming the economy so that it is compatible with biophysical limits. Great strides have been made in valuing natural capital and ecosystem services and recognizing the need to limit the scale of economic activity, but the question of how to effectively transform the economy to limit the scale of economic activity remains unclear. To gain clarity about the institutional changes necessary to limit the scale of economic activity, it is essential that ecological economics understands the limitations of its neoclassical roots and expands its theoretical framework to include how markets are embedded in social and institutional structures. This has long been the domain of institutional economics and heterodox political economy. © 2011 New York Academy of Sciences.

  13. The Development of Preschoolers' Living Kinds Concept: A Longitudinal Study

    ERIC Educational Resources Information Center

    Margett-Jordan, Tessa; Falcon, Rachael G.; Witherington, David C.

    2017-01-01

    Given limitations in the integrative scope of past research, basic questions about the organization and development of preschoolers' living kinds concept remain open to debate. This study was designed to address past limitations through use of a longitudinal design, extensive stimulus set, and alternate indices of understanding. Thirty-five…

  14. The benefits and limitations of using ultrasonography to supplement anatomical understanding.

    PubMed

    Sweetman, Greg M; Crawford, Gail; Hird, Kathryn; Fear, Mark W

    2013-01-01

    Anatomical understanding is critical to medical education. With reduced teaching time and limited cadaver availability, it is important to investigate how best to utilize in vivo imaging to supplement anatomical understanding and better prepare medical graduates for the proliferation of point-of-care imaging in the future. To investigate whether using short sessions of in vivo imaging using ultrasonography could benefit students' anatomical knowledge and clinical application, we conducted a 2-hour session on abdominal anatomy using ultrasonography in small groups of five to six students, for both first- and second-year student cohorts. Individual feedback was collected to assess student perceptions. To measure retention and understanding, a short examination containing ultrasound images and questions and performance of a clinical skill (gastrointestinal' tract examination) were assessed. Ultrasonography sessions were highly valued by the students, with 90% of the students reporting their understanding was improved, and over 70% reporting increased confidence in their anatomical knowledge. However, the assessments showed no appreciable impact on skills or understanding related to abdominal anatomy and examination. We conclude that the risk associated with limited exposure increasing confidence without increasing skills remains real and that in vivo imaging is not effective when used as a short adjunct teaching tool. The widespread use of ultrasonography means finding the best way to incorporate ultrasound into medical education remains important. To this end, we are currently implementing an extended program including echocardiography and multiple anatomical sessions that will determine if frequency and repetition of use can positively impact on student performance and understanding. Copyright © 2012 American Association of Anatomists.

  15. Status of jet noise

    NASA Technical Reports Server (NTRS)

    Banerian, G.

    1977-01-01

    The fundamentals of jet noise generation and suppression have been studied in great detail over the past twenty-five years. Considerable progress has been made recently in our understanding of this subject, though some aspects of it remain perplexing. The importance of accounting for the influence of the jets mean flow in shrouding acoustic sources is now recognized and the large amount of information obtained on jet noise reduction schemes, e.g., the internal mixer nozzle, the inverted profile nozzle and multi-element suppressors, has helped clarify trends and identify remaining issues. Current understanding of inflight effects is limited and in need of much more attention.

  16. Economic effects of ocean acidification: Publication patterns and directions for future research.

    PubMed

    Falkenberg, Laura J; Tubb, Adeline

    2017-09-01

    Human societies derive economic benefit from marine systems, yet these benefits may be modified as humans drive environmental change. Here, we conducted the first systematic review of literature on the potential economic effects of ocean acidification. We identified that while there is a growing literature discussing this topic, assessments of the direction and magnitude of anticipated economic change remain limited. The few assessments which have been conducted indicate largely negative economic effects of ocean acidification. Insights are, however, limited as the scope of the studies remains restricted. We propose that understanding of this topic will benefit from using standard approaches (e.g. timescales and emissions scenarios) to consider an increasing range of species/habitats and ecosystem services over a range of spatial scales. The resulting understanding could inform decisions such that we maintain, or enhance, economic services obtained from future marine environments.

  17. Granuloma Transplantation: An Approach to Study Mycobacterium–Host Interactions

    PubMed Central

    Harding, Jeffrey S.; Schreiber, Heidi A.; Sandor, Matyas

    2011-01-01

    The host–pathogen biology during infection with Mycobacterium tuberculosis is incredibly complex and despite accelerating progress in research, remains poorly understood. Our limited understanding hinders the development of new drugs, next generation vaccines, and novel therapies. The granuloma is the site where mycobacteria are both controlled and allowed to persist, but it remains one of the least studied aspects of the host–pathogen relationship. Here, we review the development, application, potential uses, and limitations of a novel model of granuloma transplantation as a tool to study specific host–pathogen interactions that have been difficult to probe. Application of this new model has already contributed to our understanding of granuloma cell traffic, repopulation, and the relationship between systemic immunity and mycobacteria-containing granulomas. The data collected highlight the dynamic interaction between systemic and local immune processes and support a paradigm that defines the granuloma as a highly dynamic structure. Granuloma transplantation also has special potential as a novel latency model that can contribute to our understanding of host protection factors and bacterial mutants, and serve as a platform for drug testing. PMID:22180751

  18. Absolute Paleointensity Estimates using Combined Shaw and Pseudo-Thellier Experimental Protocols

    NASA Astrophysics Data System (ADS)

    Foucher, M. S.; Smirnov, A. V.

    2016-12-01

    Data on the long-term evolution of Earth's magnetic field intensity have a great potential to advance our understanding of many aspects of the Earth's evolution. However, paleointensity determination is one of the most challenging aspects of paleomagnetic research so the quantity and quality of existing paleointensity data remain limited, especially for older epochs. While the Thellier double-heating method remains to be the most commonly used paleointensity technique, its applicability is limited for many rocks that undergo magneto-mineralogical alteration during the successive heating steps required by the method. In order to reduce the probability of alteration, several alternative methods that involve a limited number of or no heating steps have been proposed. However, continued efforts are needed to better understand the physical foundations and relative efficiency of reduced/non-heating methods in recovering the true paleofield strength and to better constrain their calibration factors. We will present the results of our investigation of synthetic and natural magnetite-bearing samples using a combination of the LTD-DHT Shaw and pseudo-Thellier experimental protocols for absolute paleointensity estimation.

  19. Applying animal behavior to arid rangeland mangement

    USDA-ARS?s Scientific Manuscript database

    Livestock production is one of many demands placed on today’s arid rangelands. Therefore, understanding plant and animal biology and their effects on biotic and abiotic landscape components is fundamental if rangelands are to remain ecologically sustainable. One limiting factor to accomplishing posi...

  20. Sustainability: What the Entrepreneurship Educators Think

    ERIC Educational Resources Information Center

    Wyness, Lynne; Jones, Paul; Klapper, Rita

    2015-01-01

    Purpose: The purpose of this paper is to consider the understanding and presence of sustainability within entrepreneurship education. The extant literature on sustainability within the entrepreneurship discipline remains extremely limited. Previously, sustainability within an entrepreneurship context has related to economic viability as opposed to…

  1. Recognising and understanding Lyme disease.

    PubMed

    Pearson, Sandra

    2014-09-09

    Lyme disease is the most common vector-borne disease in the northern hemisphere and its incidence is rising, leading to increased public health concerns. It is important to understand the nature of the disease because this defines the limitations of current understanding and knowledge. Significant uncertainties in diagnostics and treatment remain. There is an important role for the nurse in raising awareness, giving advice on prevention and correct tick removal, and in recognising signs of Lyme disease to assist access to prompt medical attention. Increased awareness, further research, improved diagnostics and advances in therapeutics are urgently required.

  2. Common Psycholinguistic Themes in Mass Murderer Manifestos

    ERIC Educational Resources Information Center

    Hamlett, Laura E.

    2017-01-01

    Mass murder in the United States is increasing, yet understanding of mass murderers is still relatively limited. Many perpetrators compose manifestos, which include journals, blogs, letters, videos, and other writings. Previous research has indicated that personal messages are of great social and psychological importance; however, there remains an…

  3. SUNLIGHT AND IRON(III)-INDUCED PHOTOCHEMICAL PRODUCTION OF DISSOLVED GASEOUS MERCURY IN FRESHWATER. (R827632)

    EPA Science Inventory

    Mechanistic understanding of sunlight-induced natural processes for
    production of dissolved gaseous mercury (DGM) in freshwaters has remained
    limited, and few direct field tests of the mechanistic hypotheses are available.
    We exposed ferric iron salt-spiked fresh s...

  4. Teacher Involvement as a Protective Factor from the Association between Race-Based Bullying and Smoking Initiation

    ERIC Educational Resources Information Center

    Earnshaw, Valerie A.; Rosenthal, Lisa; Carroll-Scott, Amy; Peters, Susan M.; McCaslin, Catherine; Ickovics, Jeannette R.

    2014-01-01

    Experiencing bullying as a victim is associated with negative health and health behavior outcomes, including substance use, among adolescents. However, understandings of protective factors--factors that enhance adolescents' resilience to the negative consequences of bullying--remain limited. The current study investigates whether teacher…

  5. Vascular Anomalies.

    PubMed

    Taghinia, Amir H; Upton, Joseph

    2018-06-12

    Vascular anomalies encompass a wide variety of clinical conditions involving the vasculature. Over the past several decades, the terminology has changed as our understanding of these conditions has improved. A well-accepted classification scheme has evolved with constant additions, updates, and revisions. Imaging techniques have also advanced with greater resolution and a better understanding of the correlation between imaging, clinical behavior, and natural history. Meanwhile, the treatment of these conditions has also changed, with greater focus on minimally invasive techniques as opposed to radical surgery. Despite these changes, surgical intervention remains a high-value option for select patients. With greater understanding of the molecular basis of these diseases, medical treatment has improved especially in severe cases where options remain limited. A multidisciplinary approach to comprehensive patient care usually yields the best outcome and is strongly encouraged. Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  6. Understanding the Low Photosynthetic Rates of Sun and Shade Coffee Leaves: Bridging the Gap on the Relative Roles of Hydraulic, Diffusive and Biochemical Constraints to Photosynthesis

    PubMed Central

    Martins, Samuel C. V.; Galmés, Jeroni; Cavatte, Paulo C.; Pereira, Lucas F.; Ventrella, Marília C.; DaMatta, Fábio M.

    2014-01-01

    It has long been held that the low photosynthetic rates (A) of coffee leaves are largely associated with diffusive constraints to photosynthesis. However, the relative limitations of the stomata and mesophyll to the overall diffusional constraints to photosynthesis, as well as the coordination of leaf hydraulics with photosynthetic limitations, remain to be fully elucidated in coffee. Whether the low actual A under ambient CO2 concentrations is associated with the kinetic properties of Rubisco and high (photo)respiration rates also remains elusive. Here, we provide a holistic analysis to understand the causes associated with low A by measuring a variety of key anatomical/hydraulic and photosynthetic traits in sun- and shade-grown coffee plants. We demonstrate that leaf hydraulic architecture imposes a major constraint on the maximisation of the photosynthetic gas exchange of coffee leaves. Regardless of the light treatments, A was mainly limited by stomatal factors followed by similar limitations associated with the mesophyll and biochemical constraints. No evidence of an inefficient Rubisco was found; rather, we propose that coffee Rubisco is well tuned for operating at low chloroplastic CO2 concentrations. Finally, we contend that large diffusive resistance should lead to large CO2 drawdown from the intercellular airspaces to the sites of carboxylation, thus favouring the occurrence of relatively high photorespiration rates, which ultimately leads to further limitations to A. PMID:24743509

  7. Understanding the contribution of common childhood illnesses and opportunistic infections to morbidity and mortality in children living with HIV in resource-limited settings.

    PubMed

    Modi, Surbhi; Chiu, Alex; Ng'eno, Bernadette; Kellerman, Scott E; Sugandhi, Nandita; Muhe, Lulu

    2013-11-01

    Although antiretroviral treatment (ART) has reduced the incidence of HIV-related opportunistic infections among children living with HIV, access to ART remains limited for children, especially in resource-limited settings. This paper reviews current knowledge on the contribution of opportunistic infections and common childhood illnesses to morbidity and mortality in children living with HIV, highlights interventions known to improve the health of children, and identifies research gaps for further exploration. Literature review of peer-reviewed articles and abstracts combined with expert opinion and operational experience. Morbidity and mortality due to opportunistic infections has decreased in both developed and resource-limited countries. However, the burden of HIV-related infections remains high, especially in sub-Saharan Africa, where the majority of HIV-infected children live. Limitations in diagnostic capacity in resource-limited settings have resulted in a relative paucity of data on opportunistic infections in children. Additionally, the reliance on clinical diagnosis means that opportunistic infections are often confused with common childhood illnesseswhich also contribute to excess morbidity and mortality in these children. Although several preventive interventions have been shown to decrease opportunistic infection-related mortality, implementation of many of these interventions remains inconsistent. In order to reduce opportunistic infection-related mortality, early ART must be expanded, training for front-line clinicians must be improved, and additional research is needed to improve screening and diagnostic algorithms.

  8. Modeling mania in preclinical settings: a comprehensive review

    PubMed Central

    Sharma, Ajaykumar N.; Fries, Gabriel R.; Galvez, Juan F.; Valvassori, Samira S.; Soares, Jair C.; Carvalho, André F.; Quevedo, Joao

    2015-01-01

    The current pathophysiological understanding of mechanisms leading to onset and progression of bipolar manic episodes remains limited. At the same time, available animal models for mania have limited face, construct, and predictive validities. Additionally, these models fail to encompass recent pathophysiological frameworks of bipolar disorder (BD), e.g. neuroprogression. Therefore, there is a need to search for novel preclinical models for mania that could comprehensively address these limitations. Herein we review the history, validity, and caveats of currently available animal models for mania. We also review new genetic models for mania, namely knockout mice for genes involved in neurotransmission, synapse formation, and intracellular signaling pathways. Furthermore, we review recent trends in preclinical models for mania that may aid in the comprehension of mechanisms underlying the neuroprogressive and recurring nature of BD. In conclusion, the validity of animal models for mania remains limited. Nevertheless, novel (e.g. genetic) animal models as well as adaptation of existing paradigms hold promise. PMID:26545487

  9. Toward a Rational and Mechanistic Account of Mental Effort.

    PubMed

    Shenhav, Amitai; Musslick, Sebastian; Lieder, Falk; Kool, Wouter; Griffiths, Thomas L; Cohen, Jonathan D; Botvinick, Matthew M

    2017-07-25

    In spite of its familiar phenomenology, the mechanistic basis for mental effort remains poorly understood. Although most researchers agree that mental effort is aversive and stems from limitations in our capacity to exercise cognitive control, it is unclear what gives rise to those limitations and why they result in an experience of control as costly. The presence of these control costs also raises further questions regarding how best to allocate mental effort to minimize those costs and maximize the attendant benefits. This review explores recent advances in computational modeling and empirical research aimed at addressing these questions at the level of psychological process and neural mechanism, examining both the limitations to mental effort exertion and how we manage those limited cognitive resources. We conclude by identifying remaining challenges for theoretical accounts of mental effort as well as possible applications of the available findings to understanding the causes of and potential solutions for apparent failures to exert the mental effort required of us.

  10. Targeted mutation of NGN3 gene disrupts pancreatic endocrine cell development in pigs

    USDA-ARS?s Scientific Manuscript database

    The domestic pig is an attractive model for biomedical research because of the similarities in anatomy and physiology to humans. However, key gaps remain in our understanding of the role of developmental genes in pig, limiting its full potential. In this publication, the role of Neurogenin 3 (NGN3)...

  11. Drought during canopy development has lasting effect on annual carbon balance in a deciduous temperate forest

    Treesearch

    Asko Noormets; Steve G. McNulty; Jared L. DeForest; Ge Sun; Qinglin Li; Jiquan Chen

    2008-01-01

    Climate change projections predict an intensifying hydrologic cycle and an increasing frequency of droughts, yet quantitative understanding of the effects on ecosystem carbon exchange remains limitedHere, the effect of contrasting precipitation and soil moisture dynamics were evaluated on forest carbon exchange using 2 yr of...

  12. Development of a Supported Self-Directed Learning Approach for Anatomy Education

    ERIC Educational Resources Information Center

    Findlater, Gordon S.; Kristmundsdottir, Fanney; Parson, Simon H.; Gillingwater, Thomas H.

    2012-01-01

    The ability to deliver sufficient core anatomical knowledge and understanding to medical students with limited time and resources remains a major challenge for anatomy educators. Here, we report the results of switching from a primarily didactic method of teaching to supported self-directed learning for students studying anatomy as part of…

  13. Youth Acquisition of Alcohol and Drinking Contexts: An In-Depth Look

    ERIC Educational Resources Information Center

    Friese, Bettina; Grube, Joel W.; Moore, Roland S.

    2013-01-01

    Despite efforts to limit underage access to alcohol, alcohol availability remains a challenge for youth drinking prevention. This article fills a gap in our understanding of alcohol consumption among youths by systematically investigating how and under what circumstances they obtain alcohol and the context within which they consume it. Qualitative…

  14. The Invisibility of Covert Bullying among Students: Challenges for School Intervention

    ERIC Educational Resources Information Center

    Barnes, Amy; Cross, Donna; Lester, Leanne; Hearn, Lydia; Epstein, Melanie; Monks, Helen

    2012-01-01

    Covert bullying behaviours are at least as distressing for young people as overt forms of bullying, but often remain unnoticed or unacknowledged by adults. This "invisibility" is increased in schools by inattention to covert bullying in policy and practice, and limited staff understanding and skill to address covert behaviours. These…

  15. Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

    DOE PAGES

    Zivcec, Marko; Scholte, Florine; Spiropoulou, Christina; ...

    2016-04-21

    Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research.

  16. Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus.

    PubMed

    Zivcec, Marko; Scholte, Florine E M; Spiropoulou, Christina F; Spengler, Jessica R; Bergeron, Éric

    2016-04-21

    Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research.

  17. Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

    PubMed Central

    Zivcec, Marko; Scholte, Florine E. M.; Spiropoulou, Christina F.; Spengler, Jessica R.; Bergeron, Éric

    2016-01-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research. PMID:27110812

  18. Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

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

    Zivcec, Marko; Scholte, Florine; Spiropoulou, Christina

    Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research.

  19. Effector and memory CD8+ T cell differentiation: toward a molecular understanding of fate determination.

    PubMed

    Belz, Gabrielle T; Kallies, Axel

    2010-06-01

    CD8(+) T cells play a key role in protecting the body against invading microorganisms. Their capacity to control infection relies on the development of peripheral effector and memory T cells. Much of our current knowledge has been gained by tracking alterations of the phenotype of CD8(+) T cells but the molecular understanding of the events that underpin the emergence of heterogeneous effector and memory CD8(+) T cells in response to infection has remained limited. This review focuses on the recent progress in our understanding of the molecular wiring of this differentiation process. Copyright 2010 Elsevier Ltd. All rights reserved.

  20. Mimetic Theory and Scapegoating in the Age of Cyberbullying: The Case of Phoebe Prince

    ERIC Educational Resources Information Center

    Norman, James O'Higgins; Connolly, Justin

    2011-01-01

    Whilst traditional forms of bullying have and continue to receive considerable attention in the literature, research on technology-enabled bullying remains in an embryonic stage and considerable deficits exist in our understanding of the nature, extent, dynamics and consequents of this new form of bullying. Of the limited studies that exist on…

  1. Are Students Drinking Hand over Fifth? Understanding Participant Demographics in Order to Curb a Dangerous Practice

    ERIC Educational Resources Information Center

    Foster, Holly A.; Bass, Ellen J.; Bruce, Susan E.

    2011-01-01

    High-risk drinking remains an issue on college campuses. Limited research focuses on drinking associated with single events where students are encouraged to drink a predetermined amount of alcohol. Fourth-year undergraduate students (N=1,205) completed a survey about motivation, behaviors and perceptions surrounding participation in a practice…

  2. Social Negotiations in a Wiki Environment: A Case Study with Pre-Service Teachers

    ERIC Educational Resources Information Center

    Vratulis, Vetta; Dobson, Teresa M.

    2008-01-01

    Understanding of the nature of social negotiations in social software spaces used in support of formal, face-to-face education remains limited. In this paper, we consider how a community of learners working collaboratively in a wiki environment established social hierarchies and negotiated power. Described is a study with 36 pre-service teachers…

  3. Conifer DBMagic: A database housing multiple de novo transcriptome assemblies for twelve diverse conifer species

    Treesearch

    W. Walter Lorenz; Savavanaraj Ayyampalayam; John M. Bordeaux; Glenn T. Howe; Kathleen D. Jermstad; David B. Neale; Deborah L. Rogers; Jeffrey F.D. Dean

    2012-01-01

    Conifers comprise an ancient and widespread plant lineage of enormous commercial and ecological value. However, compared to model woody angiosperms, such as Populus and Eucalyptus, our understanding of conifers remains quite limited at a genomic level. Large genome sizes (10,000-40,000 Mbp) and large amounts of repetitive DNA...

  4. Group Work in Physical Education: Exploring the Interconnectedness of Theoretical Approaches and Practice

    ERIC Educational Resources Information Center

    Barker, Dean; Wallhead, Tristan; Brock, Sheri; Goodyear, Victoria; Amade-Escot, Chantal

    2017-01-01

    Student group work is a central feature of many contemporary pedagogical approaches to teaching physical education. Despite this proliferation, our understanding of the teaching-learning dynamics inherent in group work remains limited and has tended to be under-theorized. The purpose of this paper was to examine different theoretical approaches to…

  5. The Threat of Common Method Variance Bias to Theory Building

    ERIC Educational Resources Information Center

    Reio, Thomas G., Jr.

    2010-01-01

    The need for more theory building scholarship remains one of the pressing issues in the field of HRD. Researchers can employ quantitative, qualitative, and/or mixed methods to support vital theory-building efforts, understanding however that each approach has its limitations. The purpose of this article is to explore common method variance bias as…

  6. Learner Satisfaction in Marketing Simulation Games: Antecedents and Influencers

    ERIC Educational Resources Information Center

    Caruana, Albert; La Rocca, Antonella; Snehota, Ivan

    2016-01-01

    Simulation games have become widespread in business courses, yet the understanding of their learning effects remains limited. The effectiveness of using simulation in marketing classes is not uniform, and not all students welcome it to the same extent. Drawing on a survey among 173 students engaged in a simulation game as part of a course in a…

  7. Molecular characterization, morphological characteristics, virulence and geographic distribution of Rhizoctonia spp. in Washington State

    USDA-ARS?s Scientific Manuscript database

    Rhizoctonia root rot and bare patch, caused by R. solani AG-8 and R. oryzae, are chronic and important yield-limiting diseases of wheat and barley in the Inland Pacific Northwest (PNW) of the USA. Major gaps remain in our understanding of the epidemiology of these diseases, and because multiple Rhiz...

  8. Is local best? Examining the evidence for local adaptation in trees and its scale

    Treesearch

    David Boshier; Linda Broadhurst; Jonathan Cornelius; Leonardo Gallo; Jarkko Koskela; Judy Loo; Gillian Petrokofsky; Brad St. Clair

    2015-01-01

    Background: Although the importance of using local provenance planting stock for woodland production, habitat conservation and restoration remains contentious, the concept is easy to understand, attractive and easy to ‘sell’. With limited information about the extent and scale of adaptive variation in native trees, discussion about suitable...

  9. Investigations into the Power MOSFET SEGR Phenomenon and its Physical Mechanism

    NASA Technical Reports Server (NTRS)

    Swift, G. M.; Edmonds, L. E.; Miyahira, T.; Nichols, D. K.; Johnston, A. H.

    1997-01-01

    The state of understanding of the destructive SEGR event in power MOSFETs is relatively mature with large published efforts, both experimental and theoretical. However, gasps remain in the uderstanding of the phenomenon, including unexplained anomalies, emperical-only dependencies on some important device and incident ion physical parameters, and limited insight into latent effets.

  10. Effective Dementia Education and Training for the Health and Social Care Workforce: A Systematic Review of the Literature

    ERIC Educational Resources Information Center

    Surr, Claire A.; Gates, Cara; Irving, Donna; Oyebode, Jan; Smith, Sarah Jane; Parveen, Sahdia; Drury, Michelle; Dennison, Alison

    2017-01-01

    Ensuring an informed and effective dementia workforce is of international concern; however, there remains limited understanding of how this can be achieved. This review aimed to identify features of effective dementia educational programs. Critical interpretive synthesis underpinned by Kirkpatrick's return on investment model was applied. One…

  11. What Are We Teaching in Diversity and Social Justice Courses? A Qualitative Content Analysis of MSW Syllabi

    ERIC Educational Resources Information Center

    Mehrotra, Gita R.; Hudson, Kimberly D.; Self, Jen M.

    2017-01-01

    Diversity and social justice are central to social work and related curricular content is mandated by accreditation standards. However, research regarding diversity and social justice courses remains limited. This study aimed to better understand how these courses are conceptualized through a qualitative content analysis of course descriptions and…

  12. Safety assessment of immunomodulatory biologics: the promise and challenges of regulatory T-cell modulation.

    PubMed

    Ponce, Rafael A

    2011-01-01

    Regulatory T-cell (T(reg)) modulation is developing as an important therapeutic opportunity for the treatment of a number of important diseases, including cancer, autoimmunity, infection, and organ transplant rejection. However, as demonstrated with IL-2 and TGN-1412, our understanding of the complex immunological interactions that occur with T(reg) modulation in both non-clinical models and in patients remains limited and appears highly contextual. This lack of understanding will challenge our ability to identify the patient population who might derive the highest benefit from T(reg) modulation and creates special challenges as we transition these therapeutics from non-clinical models into humans. Thus, in vivo testing in the most representative animal model systems, with careful progress in the clinic, will remain critical in developing therapeutics targeting T(reg) and understanding their clinical utility. Moreover, toxicology models can inform some of the potential liabilities associated with T(reg) modulation, but not all, suggesting a continued need to explore and validate predictive models.

  13. Why Do So Few Consumers Use Health Care Quality Report Cards? A Framework for Understanding the Limited Consumer Impact of Comparative Quality Information.

    PubMed

    Bhandari, Neeraj; Scanlon, Dennis P; Shi, Yunfeng; Smith, Rachel A

    2018-05-01

    Despite growing investment in producing and releasing comparative provider quality information (CQI), consumer use of CQI has remained poor. We offer a framework to interpret and synthesize the existing literature's diverse approaches to explaining the CQI's low appeal for consumers. Our framework cautions CQI stakeholders against forming unrealistic expectations of pervasive consumer use and suggests that they focus their efforts more narrowly on consumers who may find CQI more salient for choosing providers. We review the consumer impact of stakeholder efforts to apply the burgeoning knowledge of consumers' cognitive limitations to the design and dissemination of the new generation of report cards; we conclude that while it is too limited to draw firm conclusions, early evidence suggests consumers are responding to the novel design and dissemination strategies. We find that consumers continue to have difficulty accessing reliable report cards, while the media remains underused in the dissemination of report cards.

  14. Schools as Tactical Targets in Conflict: What the Case of Nepal Can Teach Us

    ERIC Educational Resources Information Center

    van Wessel, Margit; van Hirtum, Ruud

    2013-01-01

    That school grounds, students, and staff can become tactical targets for parties in conflict is widely accepted as a fact by analysts of education and conflict. However, our understanding of the motivations for such targeting remains limited, as does our ability to engage with this matter through policy. In this article we explore tactical…

  15. The (Un)Success of American Indian Gates Millennium Scholars within Institutions of Higher Education

    ERIC Educational Resources Information Center

    Youngbull, Natalie Rose

    2017-01-01

    There remains limited research on the gap between the participation and persistence to graduation rates for American Indian students in higher education. It is pertinent to explore the experiences of these students who did not persist to graduation to be able to gain a better understanding of the factors involved in this gap. The primary purpose…

  16. Aboveground and belowground mammalian herbivores regulate the demography of deciduous woody species in conifer forests

    Treesearch

    Bryan A. Endress; Bridgett J. Naylor; Burak K. Pekin; Michael J. Wisdom

    2016-01-01

    Mammalian herbivory can have profound impacts on plant population and community dynamics. However, our understanding of specific herbivore effects remains limited, even in regions with high densities of domestic and wild herbivores, such as the semiarid conifer forests of western North America. We conducted a seven-year manipulative experiment to evaluate the effects...

  17. Distinctiveness, Deference and Dominance in Black Caribbean Fathers' Engagement with Public Schools in London and New York City

    ERIC Educational Resources Information Center

    Wallace, Derron

    2017-01-01

    In the US and UK, Black fatherhood has long been steeped in narratives of pathology. Despite the promotion of nuanced understandings of Black fatherhood in recent scholarship, research on Black fathers' positive engagement with urban schools remains remarkably limited. This article adds to the literature by highlighting the strategies Black…

  18. Kinderet: Developing Training for Early Childhood Educators in Information and Communications Technology (ICT) In Bulgaria, England, Portugal, Spain and Sweden

    ERIC Educational Resources Information Center

    Saude, S.; Carioca, V.; Siraj-Blatchford, J.; Sheridan, S.; Genov, K.; Nuez, R.

    2005-01-01

    In the European context the continuing training of early childhood educators in terms of information and communications technology (ICT) remains limited and is in need of development. The KINDERET project has been funded through the European Commission's "Leonardo da Vinci" programme aimed to identify and understand the theoretical and…

  19. Current management of overactive bladder.

    PubMed

    Cartwright, Rufus; Renganathan, Arasee; Cardozo, Linda

    2008-10-01

    The concept of overactive bladder has helped us address the problem of urgency and urge incontinence from a symptomatic perspective. In this review, we provide a critical summary of clinically relevant recent publications, focusing in particular on advances in our understanding of assessment methods and therapeutic interventions for overactive bladder in women. According to current definitions, the prevalence of overactive bladder in western nations is now estimated as 13.0%. Although the prevalence increases with age, the symptoms of overactive bladder may follow a relapsing and remitting course. There has been a proliferation of validated symptom and quality of life measures and increasing sophistication in the analysis of bladder diaries. The role of urodynamics in the evaluation of urgency remains uncertain, with many trials showing limited benefit as a preoperative investigation. Fluid restriction and bladder retraining remain important first-line interventions. Many new anticholinergic medications have been licensed, with limited benefits compared with existing preparations. Intravesical botulinum toxin has become a popular alternative for patients who fail oral therapies. Although there have been few important therapeutic innovations, recent publications have led to greater sophistication in assessment methods and a clearer understanding of the role of existing interventions.

  20. Sex differences in the brain-an interplay of sex steroid hormones and sex chromosomes.

    PubMed

    Grgurevic, Neza; Majdic, Gregor

    2016-09-01

    Although considerable progress has been made in our understanding of brain function, many questions remain unanswered. The ultimate goal of studying the brain is to understand the connection between brain structure and function and behavioural outcomes. Since sex differences in brain morphology were first observed, subsequent studies suggest different functional organization of the male and female brains in humans. Sex and gender have been identified as being a significant factor in understanding human physiology, health and disease, and the biological differences between the sexes is not limited to the gonads and secondary sexual characteristics, but also affects the structure and, more crucially, the function of the brain and other organs. Significant variability in brain structures between individuals, in addition to between the sexes, is factor that complicates the study of sex differences in the brain. In this review, we explore the current understanding of sex differences in the brain, mostly focusing on preclinical animal studies. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  1. Physics-based distributed snow models in the operational arena: Current and future challenges

    NASA Astrophysics Data System (ADS)

    Winstral, A. H.; Jonas, T.; Schirmer, M.; Helbig, N.

    2017-12-01

    The demand for modeling tools robust to climate change and weather extremes along with coincident increases in computational capabilities have led to an increase in the use of physics-based snow models in operational applications. Current operational applications include the WSL-SLF's across Switzerland, ASO's in California, and USDA-ARS's in Idaho. While the physics-based approaches offer many advantages there remain limitations and modeling challenges. The most evident limitation remains computation times that often limit forecasters to a single, deterministic model run. Other limitations however remain less conspicuous amidst the assumptions that these models require little to no calibration based on their foundation on physical principles. Yet all energy balance snow models seemingly contain parameterizations or simplifications of processes where validation data are scarce or present understanding is limited. At the research-basin scale where many of these models were developed these modeling elements may prove adequate. However when applied over large areas, spatially invariable parameterizations of snow albedo, roughness lengths and atmospheric exchange coefficients - all vital to determining the snowcover energy balance - become problematic. Moreover as we apply models over larger grid cells, the representation of sub-grid variability such as the snow-covered fraction adds to the challenges. Here, we will demonstrate some of the major sensitivities of distributed energy balance snow models to particular model constructs, the need for advanced and spatially flexible methods and parameterizations, and prompt the community for open dialogue and future collaborations to further modeling capabilities.

  2. Evaluation of Current Planetary Boundary Layer Retrieval Capabilities from Space

    NASA Technical Reports Server (NTRS)

    Santanello, Joseph A., Jr.; Schaefer, Alexander J.; Blaisdell, John; Yorks, John

    2016-01-01

    The PBL over land remains a significant gap in our water and energy cycle understanding from space. This work combines unique NASA satellite and model products to demonstrate the ability of current sensors (advanced IR sounding and lidar) to retrieve PBL properties and in turn their potential to be used globally to evaluate and improve weather and climate prediction models. While incremental progress has been made in recent AIRS retrieval versions, insufficient vertical resolution remains in terms of detecting PBL properties. Lidar shows promise in terms of detecting vertical gradients (and PBLh) in the lower troposphere, but daytime conditions over land remain a challenge due to noise, and their coverage is limited to approximately 2 weeks or longer return times.

  3. The toxicity of dietary trans fats.

    PubMed

    Ganguly, Riya; Pierce, Grant N

    2015-04-01

    Cardiovascular disease remains the leading cause of death today. Trans fatty acids have been identified as an important cause of cardiovascular disease and the resulting clinical end points such as strokes and heart attacks. Although legislative efforts have limited the trans fats in our diet, significant amounts remain. Understanding the impact trans fats have on our body, therefore, remains a critical focus of study. In addition, paradoxically, recent research has now identified an important cardioprotective role for a sub-category of trans fats, the ruminant trans fats. Learning more about the mechanisms responsible for not only the toxic actions of trans fats but also their potential as beneficial compounds within our diet is essential to modulate cardiovascular disease today. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Test systems in drug discovery for hazard identification and risk assessment of human drug-induced liver injury.

    PubMed

    Weaver, Richard J; Betts, Catherine; Blomme, Eric A G; Gerets, Helga H J; Gjervig Jensen, Klaus; Hewitt, Philip G; Juhila, Satu; Labbe, Gilles; Liguori, Michael J; Mesens, Natalie; Ogese, Monday O; Persson, Mikael; Snoeys, Jan; Stevens, James L; Walker, Tracy; Park, B Kevin

    2017-07-01

    The liver is an important target for drug-induced toxicities. Early detection of hepatotoxic drugs requires use of well-characterized test systems, yet current knowledge, gaps and limitations of tests employed remains an important issue for drug development. Areas Covered: The current state of the science, understanding and application of test systems in use for the detection of drug-induced cytotoxicity, mitochondrial toxicity, cholestasis and inflammation is summarized. The test systems highlighted herein cover mostly in vitro and some in vivo models and endpoint measurements used in the assessment of small molecule toxic liabilities. Opportunities for research efforts in areas necessitating the development of specific tests and improved mechanistic understanding are highlighted. Expert Opinion: Use of in vitro test systems for safety optimization will remain a core activity in drug discovery. Substantial inroads have been made with a number of assays established for human Drug-induced Liver Injury. There nevertheless remain significant gaps with a need for improved in vitro tools and novel tests to address specific mechanisms of human Drug-Induced Liver Injury. Progress in these areas will necessitate not only models fit for application, but also mechanistic understanding of how chemical insult on the liver occurs in order to identify translational and quantifiable readouts for decision-making.

  5. Understanding Cytokine and Growth Factor Receptor Activation Mechanisms

    PubMed Central

    Atanasova, Mariya; Whitty, Adrian

    2012-01-01

    Our understanding of the detailed mechanism of action of cytokine and growth factor receptors – and particularly our quantitative understanding of the link between structure, mechanism and function – lags significantly behind our knowledge of comparable functional protein classes such as enzymes, G protein-coupled receptors, and ion channels. In particular, it remains controversial whether such receptors are activated by a mechanism of ligand-induced oligomerization, versus a mechanism in which the ligand binds to a pre-associated receptor dimer or oligomer that becomes activated through subsequent conformational rearrangement. A major limitation to progress has been the relative paucity of methods for performing quantitative mechanistic experiments on unmodified receptors expressed at endogenous levels on live cells. In this article we review the current state of knowledge on the activation mechanisms of cytokine and growth factor receptors, critically evaluate the evidence for and against the different proposed mechanisms, and highlight other key questions that remain unanswered. New approaches and techniques have led to rapid recent progress in this area, and the field is poised for major advances in the coming years, which promises to revolutionize our understanding of this large and biologically and medically important class of receptors. PMID:23046381

  6. Can Knowledge Deficit Explain Societal Perception of Climate Change Risk?

    NASA Astrophysics Data System (ADS)

    Mitra, R.; McNeal, K.; Bondell, H.

    2014-12-01

    Climate change literacy efforts have had a rough journey in the past decade. Although scientists have become increasingly convinced about anthropological climate change, change in public opinion has been underwhelming. The unexplained gap between scientific consensus and public opinion has made this topic an important research area in the realm of public understanding of science. Recent research on climate change risk perception (CCRP) has advanced an intriguing hypothesis, namely, cultural cognition thesis (CCT), which posits that the public has adequate knowledge to understand climate change science but people tend to use this knowledge solely to promote their culturally motivated view-point of climate change. This talk provides evidence to demonstrate that despite culture playing a significant role in influencing CCRP, knowledge deficiency remains a persistent problem in our society and contributes to the aforementioned gap. However, such deficits can remain undiagnosed due to limitations of survey design.

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

    PubMed Central

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

    2013-01-01

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

  8. Missed Opportunities to Prevent Workplace Injuries and Fatalities.

    PubMed

    Woolford, Marta Helen; Bugeja, Lyndal; Driscoll, Tim; Ibrahim, Joseph Elias

    2017-05-01

    Prevention efforts, especially in high-income countries, have reduced work-related death and injury. Despite this, the global incidence of workplace fatalities remains unacceptably high with approximately 317 million incidents occurring on the job annually. Of particular concern is the occurrence and re-occurrence of incidents with a similar cause and circumstance, such as fatalities occurring in agriculture and transport industries. Efforts to reduce workplace fatalities include surveillance and reporting, investigation, and regulation. Challenges remain in all three domains, limiting the prevention of work-related injuries and deaths. In this commentary, the nature of these challenges and recommendations on how to overcome them are described. Examples of incidents of workplace injury and death, as well as injury prevention efforts are provided to ensure contextual understanding. Reflecting on the present enhances key stakeholders, policy and decision-makers' understanding of the opportunities to reducing harm and the associated human, and economic and legal costs.

  9. Putting the value into biosimilar decision making: the judgment value criteria.

    PubMed

    Mendes de Abreu, Mirhelen; Strand, Vibeke; Levy, Roger Abramino; Araujo, Denizar Vianna

    2014-06-01

    Uncertainties remain the key issue surrounding biosimilars, although decisions regarding their use must be made. The challenges for policymakers, doctors, patients and others seeking to navigate in the uncharted waters of biosimilars must be clarified. At the most basic level, scientific understanding of the issue remains limited and when making decisions, policymakers must consider all those affected by health policy decisions, particularly the ultimate recipients of these medicines: the patients. The biosimilar-value chain relies on measurement of comparabilities. The goal is to demonstrate how, from a molecular perspective, closely similar they are or are not and how potential small differences may be relevant to clinical outcomes. To critically understand these points, this conceptual paper will present a knowledge-value chain and discuss each dimension assigning value in the decision making process re-utilization of biosimilars. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Critical length scale controls adhesive wear mechanisms

    PubMed Central

    Aghababaei, Ramin; Warner, Derek H.; Molinari, Jean-Francois

    2016-01-01

    The adhesive wear process remains one of the least understood areas of mechanics. While it has long been established that adhesive wear is a direct result of contacting surface asperities, an agreed upon understanding of how contacting asperities lead to wear debris particle has remained elusive. This has restricted adhesive wear prediction to empirical models with limited transferability. Here we show that discrepant observations and predictions of two distinct adhesive wear mechanisms can be reconciled into a unified framework. Using atomistic simulations with model interatomic potentials, we reveal a transition in the asperity wear mechanism when contact junctions fall below a critical length scale. A simple analytic model is formulated to predict the transition in both the simulation results and experiments. This new understanding may help expand use of computer modelling to explore adhesive wear processes and to advance physics-based wear laws without empirical coefficients. PMID:27264270

  11. Urine trouble: should we think differently about UTI?

    PubMed

    Price, Travis K; Hilt, Evann E; Dune, Tanaka J; Mueller, Elizabeth R; Wolfe, Alan J; Brubaker, Linda

    2018-02-01

    Urinary tract infection (UTI) is clinically important, given that it is one of the most common bacterial infections in adult women. However, the current understanding of UTI remains based on a now disproven concept that the urinary bladder is sterile. Thus, current standards for UTI diagnosis have significant limitations that may reduce the opportunity to improve patient care. Using data from our work and numerous other peer-reviewed studies, we identified four major limitations to the contemporary UTI description: the language of UTI, UTI diagnostic testing, the Escherichia coli-centric view of UTI, and the colony-forming units (CFU) threshold-based diagnosis. Contemporary methods and technology, combined with continued rigorous clinical research can be used to correct these limitations.

  12. "I Didn't Used to Have Much Friends": Exploring the Friendship Concepts and Capabilities of a Boy with Autism and Severe Learning Disabilities

    ERIC Educational Resources Information Center

    Potter, Carol

    2015-01-01

    Whilst progress has been made in understanding the friendships of children with autism, research on the friendships of children with additional learning disabilities remains extremely limited. In this research, a qualitative case study approach provided a rich description of the friendship concepts and capabilities of Ben, a 10-year-old boy with…

  13. Mediating water temperature increases due to livestock and global change in high elevation meadow streams of the Golden Trout Wilderness

    Treesearch

    Sebastien Nussle; Kathleen R. Matthews; Stephanie M. Carlson

    2015-01-01

    Rising temperatures due to climate change are pushing the thermal limits of many species, but how climate warming interacts with other anthropogenic disturbances such as land use remains poorly understood. To understand the interactive effects of climate warming and livestock grazing on water temperature in three high elevation meadow streams in the Golden Trout...

  14. Diabetic Cardiomyopathy: Bench to Bedside

    PubMed Central

    Schilling, Joel D.; Mann, Douglas L.

    2012-01-01

    The study of diabetic cardiomyopathy (diabetic CM) is an area of significant interest given the strong association between diabetes and the risk of heart failure. Many unanswered questions remain regarding the clinical definition and pathogenesis of this metabolic cardiomyopathy. This article reviews the current understanding of diabetic CM with a particular emphasis on the unresolved issues that have limited translation of scientific discovery to patient bedside. PMID:22999244

  15. Pathways to Genome-targeted Therapies in Serous Ovarian Cancer.

    PubMed

    Axelrod, Joshua; Delaney, Joe

    2017-07-01

    Genome sequencing technologies and corresponding oncology publications have generated enormous publicly available datasets for many cancer types. While this has enabled new treatments, and in some limited cases lifetime management of the disease, the treatment options for serous ovarian cancer remain dismal. This review summarizes recent advances in our understanding of ovarian cancer, with a focus on heterogeneity, functional genomics, and actionable data.

  16. Pathogenic Leptospira: Advances in understanding the molecular pathogenesis and virulence

    PubMed Central

    Ghazaei, Ciamak

    2018-01-01

    Leptospirosis is a common zoonotic disease has emerged as a major public health problem, with developing countries bearing disproportionate burdens. Although the diverse range of clinical manifestations of the leptospirosis in humans is widely documented, the mechanisms through which the pathogen causes disease remain undetermined. In addition, leptospirosis is a much-neglected life-threatening disease although it is one of the most important zoonoses occurring in a diverse range of epidemiological distribution. Recent advances in molecular profiling of pathogenic species of the genus Leptospira have improved our understanding of the evolutionary factors that determine virulence and mechanisms that the bacteria employ to survive. However, a major impediment to the formulation of intervention strategies has been the limited understanding of the disease determinants. Consequently, the association of the biological mechanisms to the pathogenesis of Leptospira, as well as the functions of numerous essential virulence factors still remain implicit. This review examines recent advances in genetic screening technologies, the underlying microbiological processes, the virulence factors and associated molecular mechanisms driving pathogenesis of Leptospira species. PMID:29445617

  17. Confluence of genes, environment, development, and behavior in a post Genome-Wide Association Study world.

    PubMed

    Vrieze, Scott I; Iacono, William G; McGue, Matt

    2012-11-01

    This article serves to outline a research paradigm to investigate main effects and interactions of genes, environment, and development on behavior and psychiatric illness. We provide a historical context for candidate gene studies and genome-wide association studies, including benefits, limitations, and expected payoffs. Using substance use and abuse as our driving example, we then turn to the importance of etiological psychological theory in guiding genetic, environmental, and developmental research, as well as the utility of refined phenotypic measures, such as endophenotypes, in the pursuit of etiological understanding and focused tests of genetic and environmental associations. Phenotypic measurement has received considerable attention in the history of psychology and is informed by psychometrics, whereas the environment remains relatively poorly measured and is often confounded with genetic effects (i.e., gene-environment correlation). Genetically informed designs, which are no longer limited to twin and adoption studies thanks to ever-cheaper genotyping, are required to understand environmental influences. Finally, we outline the vast amount of individual difference in structural genomic variation, most of which remains to be leveraged in genetic association tests. Although the genetic data can be massive and burdensome (tens of millions of variants per person), we argue that improved understanding of genomic structure and function will provide investigators with new tools to test specific a priori hypotheses derived from etiological psychological theory, much like current candidate gene research but with less confusion and more payoff than candidate gene research has to date.

  18. Retrograde ejaculation, painful ejaculation and hematospermia

    PubMed Central

    Parnham, Arie

    2016-01-01

    Although there has been an increased interest on premature ejaculation in the recent years, our understanding regarding the disorders of retrograde ejaculation, painful ejaculation and hematospermia remain limited. All three of these conditions require a keen clinical acumen and willingness to engage in thinking outside of the standard established treatment paradigm. The development of novel investigational techniques and treatments has led to progress in the management of these conditions symptoms; however, the literature almost uniformly is limited to small series and rare randomised trials. Further investigation and randomised controlled trials are needed for progress in these often challenging cases. PMID:27652230

  19. Trepanation and Roman medicine: a comparison of osteoarchaeological remains, material culture and written texts.

    PubMed

    Tullo, E

    2010-06-01

    Evidence for prehistoric trepanation is limited to preserved osteoarchaeological material, namely human skulls, and the occasional discovery of surgical instruments. However, the Roman empire gave rise to an abundant and diverse range of source types, including skeletal remains, material culture and detailed medical texts, each of which harbours the potential to contribute to our understanding of trepanation during this historical period. This paper highlights the advantages and inherent biases of each of these source types, and proposes that the simultaneous analysis and integration of different types of historical evidence is essential for the study of trepanation as a surgical procedure.

  20. Functional traits in agriculture: agrobiodiversity and ecosystem services.

    PubMed

    Wood, Stephen A; Karp, Daniel S; DeClerck, Fabrice; Kremen, Claire; Naeem, Shahid; Palm, Cheryl A

    2015-09-01

    Functional trait research has led to greater understanding of the impacts of biodiversity in ecosystems. Yet, functional trait approaches have not been widely applied to agroecosystems and understanding of the importance of agrobiodiversity remains limited to a few ecosystem processes and services. To improve this understanding, we argue here for a functional trait approach to agroecology that adopts recent advances in trait research for multitrophic and spatially heterogeneous ecosystems. We suggest that trait values should be measured across environmental conditions and agricultural management regimes to predict how ecosystem services vary with farm practices and environment. This knowledge should be used to develop management strategies that can be easily implemented by farmers to manage agriculture to provide multiple ecosystem services. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Clinical Manifestations and Outcomes of West Nile Virus Infection

    PubMed Central

    Sejvar, James J.

    2014-01-01

    Since the emergence of West Nile virus (WNV) in North America in 1999, understanding of the clinical features, spectrum of illness and eventual functional outcomes of human illness has increased tremendously. Most human infections with WNV remain clinically silent. Among those persons developing symptomatic illness, most develop a self-limited febrile illness. More severe illness with WNV (West Nile neuroinvasive disease, WNND) is manifested as meningitis, encephalitis or an acute anterior (polio) myelitis. These manifestations are generally more prevalent in older persons or those with immunosuppression. In the future, a more thorough understanding of the long-term physical, cognitive and functional outcomes of persons recovering from WNV illness will be important in understanding the overall illness burden. PMID:24509812

  2. Understanding International Environmental Security: A Strategic Military Perspective

    DTIC Science & Technology

    2000-11-01

    remain one of the more fragile organisms on the planet, bound to a relatively constrained set of environmental conditions of landscape, temperature...series of interwoven phenomena including, but not limited to, deforestation, 30 burning of fossil fuels, and industrial pollution. Assessing each of...burning of fossil fuels is the cause. Figure 3-7 shows the trend in carbon dioxide con- centration over the past 300 years with an expanded view since

  3. Motor Control Abnormalities in Parkinson’s Disease

    PubMed Central

    Mazzoni, Pietro; Shabbott, Britne; Cortés, Juan Camilo

    2012-01-01

    The primary manifestations of Parkinson’s disease are abnormalities of movement, including movement slowness, difficulties with gait and balance, and tremor. We know a considerable amount about the abnormalities of neuronal and muscle activity that correlate with these symptoms. Motor symptoms can also be described in terms of motor control, a level of description that explains how movement variables, such as a limb’s position and speed, are controlled and coordinated. Understanding motor symptoms as motor control abnormalities means to identify how the disease disrupts normal control processes. In the case of Parkinson’s disease, movement slowness, for example, would be explained by a disruption of the control processes that determine normal movement speed. Two long-term benefits of understanding the motor control basis of motor symptoms include the future design of neural prostheses to replace the function of damaged basal ganglia circuits, and the rational design of rehabilitation strategies. This type of understanding, however, remains limited, partly because of limitations in our knowledge of normal motor control. In this article, we review the concept of motor control and describe a few motor symptoms that illustrate the challenges in understanding such symptoms as motor control abnormalities. PMID:22675667

  4. Conversion disorder: towards a neurobiological understanding

    PubMed Central

    Harvey, Samuel B; Stanton, Biba R; David, Anthony S

    2006-01-01

    Conversion disorders are a common cause of neurological disability, but the diagnosis remains controversial and the mechanism by which psychological stress can result in physical symptoms “unconsciously” is poorly understood. This review summarises research examining conversion disorder from a neurobiological perspective. Early observations suggesting a role for hemispheric specialization have not been replicated consistently. Patients with sensory conversion symptoms have normal evoked responses in primary and secondary somatosensory cortex but a reduction in the P300 potential, which is thought to reflect a lack of conscious processing of sensory stimuli. The emergence of functional imaging has provided the greatest opportunity for understanding the neural basis of conversion symptoms. Studies have been limited by small patient numbers and failure to control for confounding variables. The evidence available would suggest a broad hypothesis that frontal cortical and limbic activation associated with emotional stress may act via inhibitory basal ganglia–thalamocortical circuits to produce a deficit of conscious sensory or motor processing. The conceptual difficulties that have limited progress in this area are discussed. A better neuropsychiatric understanding of the mechanisms of conversion symptoms may improve our understanding of normal attention and volition and reduce the controversy surrounding this diagnosis. PMID:19412442

  5. Underdetermination in evidence-based medicine.

    PubMed

    Chin-Yee, Benjamin H

    2014-12-01

    This article explores the philosophical implications of evidence-based medicine's (EBM's) epistemology in terms of the problem of underdetermination of theory by evidence as expounded by the Duhem-Quine thesis. EBM hierarchies of evidence privilege clinical research over basic science, exacerbating the problem of underdetermination. Because of severe underdetermination, EBM is unable to meaningfully test core medical beliefs that form the basis of our understanding of disease and therapeutics. As a result, EBM adopts an epistemic attitude that is sceptical of explanations from the basic biological sciences, and is relegated to a view of disease at a population level. EBM's epistemic attitude provides a limited research heuristic by preventing the development of a theoretical framework required for understanding disease mechanism and integrating knowledge to develop new therapies. Medical epistemology should remain pluralistic and include complementary approaches of basic science and clinical research, thus avoiding the limited epistemic attitude entailed by EBM hierarchies. © 2014 John Wiley & Sons, Ltd.

  6. Evolution of the Valley Position in Bulk Transition-Metal Chalcogenides and Their Monolayer Limit.

    PubMed

    Yuan, Hongtao; Liu, Zhongkai; Xu, Gang; Zhou, Bo; Wu, Sanfeng; Dumcenco, Dumitru; Yan, Kai; Zhang, Yi; Mo, Sung-Kwan; Dudin, Pavel; Kandyba, Victor; Yablonskikh, Mikhail; Barinov, Alexei; Shen, Zhixun; Zhang, Shoucheng; Huang, Yingsheng; Xu, Xiaodong; Hussain, Zahid; Hwang, Harold Y; Cui, Yi; Chen, Yulin

    2016-08-10

    Layered transition metal chalcogenides with large spin orbit coupling have recently sparked much interest due to their potential applications for electronic, optoelectronic, spintronics, and valleytronics. However, most current understanding of the electronic structure near band valleys in momentum space is based on either theoretical investigations or optical measurements, leaving the detailed band structure elusive. For example, the exact position of the conduction band valley of bulk MoS2 remains controversial. Here, using angle-resolved photoemission spectroscopy with submicron spatial resolution (micro-ARPES), we systematically imaged the conduction/valence band structure evolution across representative chalcogenides MoS2, WS2, and WSe2, as well as the thickness dependent electronic structure from bulk to the monolayer limit. These results establish a solid basis to understand the underlying valley physics of these materials, and also provide a link between chalcogenide electronic band structure and their physical properties for potential valleytronics applications.

  7. Evolution of the Valley Position in Bulk Transition-Metal Chalcogenides and Their Monolayer Limit

    DOE PAGES

    Yuan, Hongtao; Liu, Zhongkai; Xu, Gang; ...

    2016-07-12

    Valley physics based on layered transition metal chalcogenides have recently sparked much interest due to their potential spintronics and valleytronics applications. However, most current understanding of the electronic structure near band valleys in momentum space is based on either theoretical investigations or optical measurements, leaving the detailed band structure elusive. For example, the exact position of the conduction band valley of bulk MoS 2 remains controversial. Here, using angle-resolved photoemission spectroscopy with sub-micron spatial resolution (micro- ARPES), we systematically imaged the conduction/valence band structure evolution across representative chalcogenides MoS 2, WS 2 and WSe 2, as well as the thicknessmore » dependent electronic structure from bulk to the monolayer limit. These results establish a solid basis to understand the underlying valley physics of these materials, and also provide a link between chalcogenide electronic band structure and their physical properties for potential valleytronics applications.« less

  8. Pharmacogenetics of schizophrenia.

    PubMed

    Reynolds, Gavin P; Templeman, Lucy A; Godlewska, Beata R

    2006-08-01

    There is substantial unexplained interindividual variability in the drug treatment of schizophrenia. A substantial proportion of patients respond inadequately to antipsychotic drugs, and many experience limiting side effects. As genetic factors are likely to contribute to this variability, the pharmacogenetics of schizophrenia has attracted substantial effort. The approaches have mainly been limited to association studies of polymorphisms in candidate genes, which have been indicated by the pharmacology of antipsychotic drugs. Although some advances have been made, particularly in understanding the pharmacogenetics of some limiting side effects, genetic prediction of symptom response remains elusive. Nevertheless, with improvements in defining the response phenotype in carefully assessed and homogeneous subject groups, the near future is likely to see the identification of genetic predictors of outcome that may inform the choice of pharmacotherapy.

  9. Molecular mechanisms influencing efficiency of RNA interference in insects.

    PubMed

    Cooper, Anastasia M W; Silver, Kristopher; Jianzhen, Zhang; Park, Yoonseong; Zhu, Kun Yan

    2018-06-21

    RNA interference (RNAi) is an endogenous, sequence-specific gene silencing mechanism elicited by small RNA molecules. RNAi is a powerful reverse genetic tool, and is currently being utilized for managing insects and viruses. Widespread implementation of RNAi-based pest management strategies is currently hindered by inefficient and highly variable results when different insect species, strains, developmental stages, tissues, and genes are targeted. Mechanistic studies have shown that double-stranded ribonucleases (dsRNases), endosomal entrapment, deficient function of the core machinery, and inadequate immune stimulation contribute to limited RNAi efficiency. However, a comprehensive understanding of the molecular mechanisms limiting RNAi efficiency remains elusive. The recent advances in dsRNA stability in physiological tissues, dsRNA internalization into cells, the composition and function of the core RNAi machinery, as well as small-interfering RNA/double-stranded RNA amplification and spreading mechanisms are reviewed to establish a global understanding of the obstacles impeding wider understanding of RNAi mechanisms in insects. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Carbon Budgets as a Guide to Deep Decarbonisation

    NASA Astrophysics Data System (ADS)

    Rogelj, J.

    2017-12-01

    Halting global mean temperature rise requires a limit on the cumulative amount of net CO2 disposed of in the atmosphere. Remaining within the limits of such carbon budgets over the 21st century will require a profound transformation of how our societies use and produce energy, crops, and materials. To understand the options available to stay within stringent carbon budget constraints, global transformation pathways are being devised with integrated models of the energy-economy-land system. This presentation will look at how the latest insights of such pathways affect carbon budgets. Estimates of carbon budgets compatible with a given temperature limit depend on the anticipated temperature contribution at peak warming of non-CO2 forcers. Integrated transformation pathways allow to understand the projected extend of these contributions, as well as estimate the maximum conceivable rate of emissions reductions over the coming decades. The latter directly informs the lower end of future cumulative CO2 emissions and can thus provide an estimate for minimum peak warming over the 21st century - a measure which can be compared to the ambitious long-term temperature goal of the UNFCCC Paris Agreement.

  11. Ionic-Electronic Ambipolar Transport in Metal Halide Perovskites: Can Electronic Conductivity Limit Ionic Diffusion?

    PubMed

    Kerner, Ross A; Rand, Barry P

    2018-01-04

    Ambipolar transport describes the nonequilibrium, coupled motion of positively and negatively charged particles to ensure that internal electric fields remain small. It is commonly invoked in the semiconductor community where the motion of excess electrons and holes drift and diffuse together. However, the concept of ambipolar transport is not limited to semiconductor physics. Materials scientists working on ion conducting ceramics understand ambipolar transport dictates the coupled diffusion of ions and the rate is limited by the ion with the lowest diffusion coefficient. In this Perspective, we review a third application of ambipolar transport relevant to mixed ionic-electronic conducting materials for which the motion of ions is expected to be coupled to electronic carriers. In this unique situation, the ambipolar diffusion model has been successful at explaining the photoenhanced diffusion of metal ions in chalcogenide glasses and other properties of materials. Recent examples of photoenhanced phenomena in metal halide perovskites are discussed and indicate that mixed ionic-electronic ambipolar transport is similarly important for a deep understanding of these emerging materials.

  12. A Guide to Non-Alcoholic Fatty Liver Disease in Childhood and Adolescence

    PubMed Central

    Temple, Jonathan L.; Cordero, Paul; Li, Jiawei; Nguyen, Vi; Oben, Jude A.

    2016-01-01

    Non-Alcoholic Fatty Liver Disease (NAFLD) is now the most prevalent form of chronic liver disease, affecting 10%–20% of the general paediatric population. Within the next 10 years it is expected to become the leading cause of liver pathology, liver failure and indication for liver transplantation in childhood and adolescence in the Western world. While our understanding of the pathophysiological mechanisms underlying this disease remains limited, it is thought to be the hepatic manifestation of more widespread metabolic dysfunction and is strongly associated with a number of metabolic risk factors, including insulin resistance, dyslipidaemia, cardiovascular disease and, most significantly, obesity. Despite this, ”paediatric” NAFLD remains under-studied, under-recognised and, potentially, undermanaged. This article will explore and evaluate our current understanding of NAFLD in childhood and adolescence and how it differs from adult NAFLD, in terms of its epidemiology, pathophysiology, natural history, diagnosis and clinical management. Given the current absence of definitive radiological and histopathological diagnostic tests, maintenance of a high clinical suspicion by all members of the multidisciplinary team in primary and specialist care settings remains the most potent of diagnostic tools, enabling early diagnosis and appropriate therapeutic intervention. PMID:27314342

  13. An integrated view of cisplatin-induced nephrotoxicity and ototoxicity

    PubMed Central

    Karasawa, Takatoshi; Steyger, Peter S.

    2015-01-01

    Cisplatin is one of the most widely-used drugs to treat cancers. However, its nephrotoxic and ototoxic side-effects remain major clinical limitations. Recent studies have improved our understanding of the molecular mechanisms of cisplatin-induced nephrotoxicity and ototoxicity. While cisplatin binding to DNA is the major cytotoxic mechanism in proliferating (cancer) cells, nephrotoxicity and ototoxicity appear to result from toxic levels of reactive oxygen species and protein dysregulation within various cellular compartments. In this review, we discuss molecular mechanisms of cisplatin-induced nephrotoxicity and ototoxicity. We also discuss potential clinical strategies to prevent nephrotoxicity and ototoxicity and their current limitations. PMID:26101797

  14. A Quantitative Chemotherapy Genetic Interaction Map Reveals Factors Associated with PARP Inhibitor Resistance. | Office of Cancer Genomics

    Cancer.gov

    Chemotherapy is used to treat most cancer patients, yet our understanding of factors that dictate response and resistance to such drugs remains limited. We report the generation of a quantitative chemical-genetic interaction map in human mammary epithelial cells charting the impact of the knockdown of 625 genes related to cancer and DNA repair on sensitivity to 29 drugs, covering all classes of chemotherapy.

  15. Understanding Environmental Security: A Military Perspective

    DTIC Science & Technology

    2000-06-14

    rates, which humankind can impact only in minor percentages of total use. In the final analysis we remain one of the more fragile organisms on the planet...by. a series of interwoven phenomenon including but not limited to deforestation. burning of fossil ftiels. industrial pollution. and urbanization...burning of fossil fuels is the cause. Figure 1-7 shows the trend in carbon dioxide concentration over the past 300 years with an expanded view since 1960

  16. A quantitative chemotherapy genetic interaction map reveals new factors associated with PARP inhibitor resistance | Office of Cancer Genomics

    Cancer.gov

    Nearly every cancer patient is treated with chemotherapy yet our understanding of factors that dictate response and resistance to such agents remains limited. We report the generation of a quantitative chemical-genetic interaction map in human mammary epithelial cells that charts the impact of knockdown of 625 cancer and DNA repair related genes on sensitivity to 29 drugs, covering all classes of cancer chemotherapeutics.

  17. Fusion in posttraumatic foot and ankle reconstruction.

    PubMed

    Thordarson, David B

    2004-01-01

    Despite appropriate acute treatment, many foot and ankle injuries result in posttraumatic arthritis. Arthrodesis remains the mainstay of treatment of end-stage arthritis of the foot and ankle. An understanding of the biomechanics of the foot and ankle, particularly which joints are most responsible for optimal function of the foot, can help guide reconstructive efforts. A careful history and physical examination, appropriate radiographs, and, when necessary, differential selective anesthetic blocks help limit fusion to only those joints that are causing pain. Compression fixation, when possible, remains the treatment of choice. When bone defects are present, however, neutralization fixation may be necessary to prevent a secondary deformity that could result from impaction into a bone defect.

  18. Spectral Dependence of MODIS Cloud Droplet Effective Radius Retrievals for Marine Boundary Layer Clouds

    NASA Technical Reports Server (NTRS)

    Zhang, Zhibo; Platnick, Steven E.; Ackerman, Andrew S.; Cho, Hyoun-Myoung

    2014-01-01

    Low-level warm marine boundary layer (MBL) clouds cover large regions of Earth's surface. They have a significant role in Earth's radiative energy balance and hydrological cycle. Despite the fundamental role of low-level warm water clouds in climate, our understanding of these clouds is still limited. In particular, connections between their properties (e.g. cloud fraction, cloud water path, and cloud droplet size) and environmental factors such as aerosol loading and meteorological conditions continue to be uncertain or unknown. Modeling these clouds in climate models remains a challenging problem. As a result, the influence of aerosols on these clouds in the past and future, and the potential impacts of these clouds on global warming remain open questions leading to substantial uncertainty in climate projections. To improve our understanding of these clouds, we need continuous observations of cloud properties on both a global scale and over a long enough timescale for climate studies. At present, satellite-based remote sensing is the only means of providing such observations.

  19. Trophic interactions induce spatial self-organization of microbial consortia on rough surfaces.

    PubMed

    Wang, Gang; Or, Dani

    2014-10-24

    The spatial context of microbial interactions common in natural systems is largely absent in traditional pure culture-based microbiology. The understanding of how interdependent microbial communities assemble and coexist in limited spatial domains remains sketchy. A mechanistic model of cell-level interactions among multispecies microbial populations grown on hydrated rough surfaces facilitated systematic evaluation of how trophic dependencies shape spatial self-organization of microbial consortia in complex diffusion fields. The emerging patterns were persistent irrespective of initial conditions and resilient to spatial and temporal perturbations. Surprisingly, the hydration conditions conducive for self-assembly are extremely narrow and last only while microbial cells remain motile within thin aqueous films. The resulting self-organized microbial consortia patterns could represent optimal ecological templates for the architecture that underlie sessile microbial colonies on natural surfaces. Understanding microbial spatial self-organization offers new insights into mechanisms that sustain small-scale soil microbial diversity; and may guide the engineering of functional artificial microbial consortia.

  20. Molecular Aspects of Head and Neck Cancer Therapy

    PubMed Central

    Puram, Sidharth V.; Rocco, James W.

    2015-01-01

    Synopsis In spite of a rapidly expanding understanding of head and neck tumor biology as well as optimization of radiation, chemotherapy, and surgical treatment modalities, head and neck squamous cell carcinoma (HNSCC) remains a major cause of cancer related morbidity and mortality. Although our biologic understanding of these tumors had largely been limited to pathways driving proliferation, survival, and differentiation, the identification of HPV as a major driver of HNSCC, specifically oropharyngeal SCC, as well as recent genomic sequencing analyses of HNSCC has dramatically influenced our understanding of the underlying biology behind carcinogenesis, and in part, our approach to therapy. In particular, we are at a major molecular and clinical crossroads with an explosion of promising diagnostic and therapeutic agents that hold great promise. Here, we summarize our current understanding of HNSCC biology, including a review of recent sequencing analyses, and identify promising areas for potential diagnostic and therapeutic agents. PMID:26568543

  1. Carbon Metabolism of Prochlorococcus sp. Under Nitrogen Limitation

    NASA Astrophysics Data System (ADS)

    Szul, M.

    2016-02-01

    Phytoplankton growth rates are limited by nutrient availability in the world's euphotic oligotrophic oceans. In these vast biomes, convergent evolutions of the dominant planktonic populations suggest traits such as small genome and cell size provide selective advantages. While these traits have been shown to improve both thrift and competition for scarce nutrients, how fitness is manifest through reductive evolution on metabolisms remains poorly understood. To develop a better understanding of carbon fate and flux under nutrient limitation, we grew axenic Prochlorococcus under nitrogen-limited and nitrogen-replete conditions and measured metabolite pools, the flux of carbon through these pools as well as photosynthesis, photosystem health and efficiency. Our data show cells under nitrogen limitation reduce rates of both metabolite flux and total carbon fixation while maintaining elevated metabolite pool levels and releasing a larger proportion of total fixed carbon to the environment. Accounting for these observations, potential metabolic mechanisms that contribute to the fitness of Prochlorococcus in the nutrient limited oceans will be discussed.

  2. Sonocrystallization-application of radiation forces from acoustic standing waves for configurable assembly

    NASA Astrophysics Data System (ADS)

    Shields, Charles

    Acoustic radiation forces offer a promising approach to rapidly arrange particles across a broad range of scales, yet it remains largely unexplored compared to classical methods like centrifugation, electrophoresis, and magnetophoresis. Acoustic forces offer numerous advantages, including scalability, programmability, and the ability to manipulate particles of variable composition (i.e., without narrowly defined electromagnetic or other properties). While some groups have shown the ability to concentrate particles with ultrasonic radiation, the capabilities and limitations for precise particle assembly and morphological control remain poorly understood. Here, I will discuss our recent efforts to explore the flexibility and limitations of acoustophoresis to rapidly arrange microparticles into organized and programmable structures. In order to execute these studies, we employ a simple ``sonocrystallization chamber'' that creates multidimensional bulk acoustic standing waves to propel particles toward the pressure nodes or antinodes, depending on their contrast factor. We can thus create thousands of size-limited assemblies within minutes. We pair these experiments with simulations and theory to model the migration kinetics and assembly patterns of different particles types. I will further discuss how we have extended these results to understand the lower particle size limit for assembly in systems such as gold nanoparticles with diameters <200 nm. Finally, I will show how we incorporated a simple light-based crosslinking approach for stabilizing the assembly in the small particle limit (i.e., beyond the acoustic focusing limit), which might enable use in a variety of plasmonic and photonic applications.

  3. Modulation of telomere binding proteins: a future area of research for skin protection and anti-aging target.

    PubMed

    Imbert, Isabelle; Botto, Jean-Marie; Farra, Claude D; Domloge, Nouha

    2012-06-01

    Telomere shortening is considered as one of the main characteristics of cellular aging by limiting cellular division. Besides the fundamental advances through the discoveries of telomere and telomerase, which were recognized by a Nobel Prize, telomere protection remains an essential area of research. Recently, it was evidenced that studying the cross-talks between the proteins associated with telomere should provide a better understanding of the mechanistic basis for telomere-associated aging phenotypes. In this review, we discuss the current knowledge on telomere shortening, telomerase activity, and the essential role of telomere binding proteins in telomere stabilization and telomere-end protection. This review highlights the capacity of telomere binding proteins to limit cellular senescence and to maintain skin tissue homeostasis, which is of key importance to reduce accelerated tissue aging. Future studies addressing telomere protection and limitation of DNA damage response in human skin should include investigations on telomere binding proteins. As little is known about the expression of telomere binding proteins in human skin and modulation of their expression with aging, it remains an interesting field of skin research and a key area for future skin protection and anti-aging developments. © 2012 Wiley Periodicals, Inc.

  4. Casuistry as common law morality.

    PubMed

    Paulo, Norbert

    2015-12-01

    This article elaborates on the relation between ethical casuistry and common law reasoning. Despite the frequent talk of casuistry as common law morality, remarks on this issue largely remain at the purely metaphorical level. The article outlines and scrutinizes Albert Jonsen and Stephen Toulmin's version of casuistry and its basic elements. Drawing lessons for casuistry from common law reasoning, it is argued that one generally has to be faithful to ethical paradigms. There are, however, limitations for the binding force of paradigms. The most important limitations--the possibilities of overruling and distinguishing paradigm norms--are similar in common law and in casuistry, or so it is argued. These limitations explain why casuistry is not necessarily overly conservative and conventional, which is one line of criticism to which casuists can now better respond. Another line of criticism has it that the very reasoning from case to case is extremely unclear in casuistry. I suggest a certain model of analogical reasoning to address this critique. All my suggestions to understand and to enhance casuistry make use of common law reasoning whilst remaining faithful to Jonsen and Toulmin's main ideas and commitments. Further developed along these lines, casuistry can appropriately be called "common law morality."

  5. The Molecular Biology of Adenoid Cystic Carcinoma

    PubMed Central

    Liu, Jia; Shao, Chunbo; Tan, Marietta L.; Mu, David; Ferris, Robert L.; Ha, Patrick K.

    2011-01-01

    Background Adenoid cystic carcinoma (ACC) is an unusual salivary gland malignancy that remains poorly understood. Standard treatment, including surgery with postoperative radiation therapy have attained reasonable local control rates, but the propensity for distant metastases has limited any improvement in survival over time. Our understanding of the molecular mechanisms driving adenoid cystic carcinoma is quite rudimentary, due to the infrequent nature of its occurrence. Methods An extensive literature review was performed on salivary gland adenoid cystic carcinoma and basic science research findings. Results This review highlights many findings that are emerging about the carcinogenesis of ACC including cytogenetics, tumor suppressor genes, oncogenes, epigenetic alterations, mitochondrial alterations, and biomarker studies. Conclusions While there have been many discoveries, much still remains unknown about this rare malignancy. PMID:22006498

  6. The importance of pro-inflammatory signaling in neonatal NEC

    PubMed Central

    Frost, Brandy L.; Jilling, Tamas; Caplan, Michael S.

    2008-01-01

    Despite modern medical advances, necrotizing enterocolitis (NEC) remains a significant cause of morbidity and mortality in neonatal intensive care units, affecting 10 percent of premature neonates born weighing less than 1500 grams. Although many advances have been made in the understanding of this disease, the etiology and pathophysiology remain incompletely understood, and treatment is limited to supportive care. In recent years, studies have focused on the role of the inflammatory cascade and its’ impact on the disease process, and investigators are evaluating strategies to attenuate inflammatory signaling that might prevent and/or ameliorate neonatal NEC. In this review, we examine the key points in the signaling pathways involved in NEC, and potential strategies for prevention and treatment of this dreaded disease. PMID:18346533

  7. Nuclear fuel in a reactor accident.

    PubMed

    Burns, Peter C; Ewing, Rodney C; Navrotsky, Alexandra

    2012-03-09

    Nuclear accidents that lead to melting of a reactor core create heterogeneous materials containing hundreds of radionuclides, many with short half-lives. The long-lived fission products and transuranium elements within damaged fuel remain a concern for millennia. Currently, accurate fundamental models for the prediction of release rates of radionuclides from fuel, especially in contact with water, after an accident remain limited. Relatively little is known about fuel corrosion and radionuclide release under the extreme chemical, radiation, and thermal conditions during and subsequent to a nuclear accident. We review the current understanding of nuclear fuel interactions with the environment, including studies over the relatively narrow range of geochemical, hydrological, and radiation environments relevant to geological repository performance, and discuss priorities for research needed to develop future predictive models.

  8. Novel Stroke Therapeutics: Unraveling Stroke Pathophysiology and Its Impact on Clinical Treatments

    PubMed Central

    George, Paul M.; Steinberg, Gary K.

    2016-01-01

    Stroke remains a leading cause of death and disability in the world. Over the past few decades our understanding of the pathophysiology of stroke has increased, but greater insight is required to advance the field of stroke recovery. Clinical treatments have improved in the acute time window, but long-term therapeutics remain limited. Complex neural circuits damaged by ischemia make restoration of function after stroke difficult. New therapeutic approaches, including cell transplantation or stimulation, focus on reestablishing these circuits through multiple mechanisms to improve circuit plasticity and remodeling. Other research targets intact networks to compensate for damaged regions. This review highlights several important mechanisms of stroke injury and describes emerging therapies aimed at improving clinical outcomes. PMID:26182415

  9. Mechanistic kinetic models of enzymatic cellulose hydrolysis-A review.

    PubMed

    Jeoh, Tina; Cardona, Maria J; Karuna, Nardrapee; Mudinoor, Akshata R; Nill, Jennifer

    2017-07-01

    Bioconversion of lignocellulose forms the basis for renewable, advanced biofuels, and bioproducts. Mechanisms of hydrolysis of cellulose by cellulases have been actively studied for nearly 70 years with significant gains in understanding of the cellulolytic enzymes. Yet, a full mechanistic understanding of the hydrolysis reaction has been elusive. We present a review to highlight new insights gained since the most recent comprehensive review of cellulose hydrolysis kinetic models by Bansal et al. (2009) Biotechnol Adv 27:833-848. Recent models have taken a two-pronged approach to tackle the challenge of modeling the complex heterogeneous reaction-an enzyme-centric modeling approach centered on the molecularity of the cellulase-cellulose interactions to examine rate limiting elementary steps and a substrate-centric modeling approach aimed at capturing the limiting property of the insoluble cellulose substrate. Collectively, modeling results suggest that at the molecular-scale, how rapidly cellulases can bind productively (complexation) and release from cellulose (decomplexation) is limiting, while the overall hydrolysis rate is largely insensitive to the catalytic rate constant. The surface area of the insoluble substrate and the degrees of polymerization of the cellulose molecules in the reaction both limit initial hydrolysis rates only. Neither enzyme-centric models nor substrate-centric models can consistently capture hydrolysis time course at extended reaction times. Thus, questions of the true reaction limiting factors at extended reaction times and the role of complexation and decomplexation in rate limitation remain unresolved. Biotechnol. Bioeng. 2017;114: 1369-1385. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  10. Political and institutional influences on the use of evidence in public health policy. A systematic review.

    PubMed

    Liverani, Marco; Hawkins, Benjamin; Parkhurst, Justin O

    2013-01-01

    There is increasing recognition that the development of evidence-informed health policy is not only a technical problem of knowledge exchange or translation, but also a political challenge. Yet, while political scientists have long considered the nature of political systems, the role of institutional structures, and the political contestation of policy issues as central to understanding policy decisions, these issues remain largely unexplored by scholars of evidence-informed policy making. We conducted a systematic review of empirical studies that examined the influence of key features of political systems and institutional mechanisms on evidence use, and contextual factors that may contribute to the politicisation of health evidence. Eligible studies were identified through searches of seven health and social sciences databases, websites of relevant organisations, the British Library database, and manual searches of academic journals. Relevant findings were extracted using a uniform data extraction tool and synthesised by narrative review. 56 studies were selected for inclusion. Relevant political and institutional aspects affecting the use of health evidence included the level of state centralisation and democratisation, the influence of external donors and organisations, the organisation and function of bureaucracies, and the framing of evidence in relation to social norms and values. However, our understanding of such influences remains piecemeal given the limited number of empirical analyses on this subject, the paucity of comparative works, and the limited consideration of political and institutional theory in these studies. This review highlights the need for a more explicit engagement with the political and institutional factors affecting the use of health evidence in decision-making. A more nuanced understanding of evidence use in health policy making requires both additional empirical studies of evidence use, and an engagement with theories and approaches beyond the current remit of public health or knowledge utilisation studies.

  11. Achieving quantum precision limit in adaptive qubit state tomography

    NASA Astrophysics Data System (ADS)

    Hou, Zhibo; Zhu, Huangjun; Xiang, Guo-Yong; Li, Chuan-Feng; Guo, Guang-Can

    2016-02-01

    The precision limit in quantum state tomography is of great interest not only to practical applications but also to foundational studies. However, little is known about this subject in the multiparameter setting even theoretically due to the subtle information trade-off among incompatible observables. In the case of a qubit, the theoretic precision limit was determined by Hayashi as well as Gill and Massar, but attaining the precision limit in experiments has remained a challenging task. Here we report the first experiment that achieves this precision limit in adaptive quantum state tomography on optical polarisation qubits. The two-step adaptive strategy used in our experiment is very easy to implement in practice. Yet it is surprisingly powerful in optimising most figures of merit of practical interest. Our study may have significant implications for multiparameter quantum estimation problems, such as quantum metrology. Meanwhile, it may promote our understanding about the complementarity principle and uncertainty relations from the information theoretic perspective.

  12. Intraoperative bronchoscopic visualization of left ventricular assist device thrombus.

    PubMed

    Yost, Gardner; Bhat, Geetha; Modi, Sejal; Pappas, Pat; Tatooles, Antone

    2016-07-01

    Despite advancements in left ventricular assist device (LVAD) design and clinical management, device thrombosis remains a pertinent complication. Limited imaging makes precise visualization of clot location and shape very challenging. We report the usage of videobronchoscopic exploration of explanted LVADs for direct visualization of clot in two patients. This technique is a rapid and inexpensive means of improving our understanding of LVAD clot formation and may be useful in surgical exploration of inflow and outflow tracts during LVAD exchange. © The Author(s) 2015.

  13. Capacity and precision in an animal model of visual short-term memory.

    PubMed

    Lara, Antonio H; Wallis, Jonathan D

    2012-03-14

    Temporary storage of information in visual short-term memory (VSTM) is a key component of many complex cognitive abilities. However, it is highly limited in capacity. Understanding the neurophysiological nature of this capacity limit will require a valid animal model of VSTM. We used a multiple-item color change detection task to measure macaque monkeys' VSTM capacity. Subjects' performance deteriorated and reaction times increased as a function of the number of items in memory. Additionally, we measured the precision of the memory representations by varying the distance between sample and test colors. In trials with similar sample and test colors, subjects made more errors compared to trials with highly discriminable colors. We modeled the error distribution as a Gaussian function and used this to estimate the precision of VSTM representations. We found that as the number of items in memory increases the precision of the representations decreases dramatically. Additionally, we found that focusing attention on one of the objects increases the precision with which that object is stored and degrades the precision of the remaining. These results are in line with recent findings in human psychophysics and provide a solid foundation for understanding the neurophysiological nature of the capacity limit of VSTM.

  14. Escape rate for nonequilibrium processes dominated by strong non-detailed balance force

    NASA Astrophysics Data System (ADS)

    Tang, Ying; Xu, Song; Ao, Ping

    2018-02-01

    Quantifying the escape rate from a meta-stable state is essential to understand a wide range of dynamical processes. Kramers' classical rate formula is the product of an exponential function of the potential barrier height and a pre-factor related to the friction coefficient. Although many applications of the rate formula focused on the exponential term, the prefactor can have a significant effect on the escape rate in certain parameter regions, such as the overdamped limit and the underdamped limit. There have been continuous interests to understand the effect of non-detailed balance on the escape rate; however, how the prefactor behaves under strong non-detailed balance force remains elusive. In this work, we find that the escape rate formula has a vanishing prefactor with decreasing friction strength under the strong non-detailed balance limit. We both obtain analytical solutions in specific examples and provide a derivation for more general cases. We further verify the result by simulations and propose a testable experimental system of a charged Brownian particle in electromagnetic field. Our study demonstrates that a special care is required to estimate the effect of prefactor on the escape rate when non-detailed balance force dominates.

  15. Understanding heart rate alarm adjustment in the intensive care units through an analytical approach.

    PubMed

    Fidler, Richard L; Pelter, Michele M; Drew, Barbara J; Palacios, Jorge Arroyo; Bai, Yong; Stannard, Daphne; Aldrich, J Matt; Hu, Xiao

    2017-01-01

    Heart rate (HR) alarms are prevalent in ICU, and these parameters are configurable. Not much is known about nursing behavior associated with tailoring HR alarm parameters to individual patients to reduce clinical alarm fatigue. To understand the relationship between heart rate (HR) alarms and adjustments to reduce unnecessary heart rate alarms. Retrospective, quantitative analysis of an adjudicated database using analytical approaches to understand behaviors surrounding parameter HR alarm adjustments. Patients were sampled from five adult ICUs (77 beds) over one month at a quaternary care university medical center. A total of 337 of 461 ICU patients had HR alarms with 53.7% male, mean age 60.3 years, and 39% non-Caucasian. Default HR alarm parameters were 50 and 130 beats per minute (bpm). The occurrence of each alarm, vital signs, and physiologic waveforms was stored in a relational database (SQL server). There were 23,624 HR alarms for analysis, with 65.4% exceeding the upper heart rate limit. Only 51% of patients with HR alarms had parameters adjusted, with a median upper limit change of +5 bpm and -1 bpm lower limit. The median time to first HR parameter adjustment was 17.9 hours, without reduction in alarms occurrence (p = 0.57). HR alarms are prevalent in ICU, and half of HR alarm settings remain at default. There is a long delay between HR alarms and parameters changes, with insufficient changes to decrease HR alarms. Increasing frequency of HR alarms shortens the time to first adjustment. Best practice guidelines for HR alarm limits are needed to reduce alarm fatigue and improve monitoring precision.

  16. A developmental and genetic classification for midbrain-hindbrain malformations

    PubMed Central

    Millen, Kathleen J.; Dobyns, William B.

    2009-01-01

    Advances in neuroimaging, developmental biology and molecular genetics have increased the understanding of developmental disorders affecting the midbrain and hindbrain, both as isolated anomalies and as part of larger malformation syndromes. However, the understanding of these malformations and their relationships with other malformations, within the central nervous system and in the rest of the body, remains limited. A new classification system is proposed, based wherever possible, upon embryology and genetics. Proposed categories include: (i) malformations secondary to early anteroposterior and dorsoventral patterning defects, or to misspecification of mid-hindbrain germinal zones; (ii) malformations associated with later generalized developmental disorders that significantly affect the brainstem and cerebellum (and have a pathogenesis that is at least partly understood); (iii) localized brain malformations that significantly affect the brain stem and cerebellum (pathogenesis partly or largely understood, includes local proliferation, cell specification, migration and axonal guidance); and (iv) combined hypoplasia and atrophy of putative prenatal onset degenerative disorders. Pertinent embryology is discussed and the classification is justified. This classification will prove useful for both physicians who diagnose and treat patients with these disorders and for clinical scientists who wish to understand better the perturbations of developmental processes that produce them. Importantly, both the classification and its framework remain flexible enough to be easily modified when new embryologic processes are described or new malformations discovered. PMID:19933510

  17. Relieving existential suffering through palliative sedation: discussion of an uneasy practice.

    PubMed

    Bruce, Anne; Boston, Patricia

    2011-12-01

    This article presents a discussion of the use of palliative sedation in response to intractable (not responsive to treatment) existential suffering. Patients suffering from a terminal illness are often faced with severe symptoms at the end of life. Although palliative sedation is sometimes used when no other options are effective in relieving unbearable pain or suffering, its use in response to intractable existential suffering in terminal illness remains controversial. A literature search was conducted for published articles addressing the use of palliative sedation between 1996 and 2009 using established databases. Palliative sedation remains an uneasy practice. The debates have centred on ethical issues surrounding decisions to use sedation and on separating the intent of palliative sedation (relief of intolerable symptoms) from the intent of euthanasia (hastening death). There is lack of consensus in defining existential suffering. Consequently, there is limited understanding of how decisions are being made when using palliative sedation to treat intractable existential suffering. Given the confusion and uncertainty about ethical and clinical justifications for palliative sedation in treating existential suffering, we argue that a better understanding of the controversies and decision-making process is needed. Greater understanding is required to prevent palliative sedation from becoming a substitute for intensive treatment of this kind of suffering. © 2011 Blackwell Publishing Ltd.

  18. Culicoides Latreille (Diptera: Ceratopogonidae) taxonomy: Current challenges and future directions

    PubMed Central

    Harrup, L.E.; Bellis, G.A.; Balenghien, T.; Garros, C.

    2015-01-01

    Culicoides Latreille biting midges (Diptera: Ceratopogonidae) cause a significant biting nuisance to humans, livestock and equines, and are the biological vectors of a range of internationally important pathogens of both veterinary and medical importance. Despite their economic significance, the delimitation and identification of species and evolutionary relationships between species within this genus remains at best problematic. To date no phylogenetic study has attempted to validate the subgeneric classification of the genus and the monophyly of many of the subgenera remains doubtful. Many informal species groupings are also known to exist but few are adequately described, further complicating accurate identification. Recent contributions to Culicoides taxonomy at the species level have revealed a high correlation between morphological and molecular analyses although molecular analyses are revealing the existence of cryptic species. This review considers the methods for studying the systematics of Culicoides using both morphological and genetic techniques, with a view to understanding the factors limiting our current understanding of Culicoides biology and hence arbovirus epidemiology. In addition, we examine the global status of Culicoides identification, highlighting areas that are poorly addressed, including the potential implementation of emerging technologies. PMID:25535946

  19. A resurgence in field research is essential to better understand the diversity, ecology, and evolution of microbial eukaryotes.

    PubMed

    Heger, Thierry J; Edgcomb, Virginia P; Kim, Eunsoo; Lukeš, Julius; Leander, Brian S; Yubuki, Naoji

    2014-01-01

    The discovery and characterization of protist communities from diverse environments are crucial for understanding the overall evolutionary history of life on earth. However, major questions about the diversity, ecology, and evolutionary history of protists remain unanswered, notably because data obtained from natural protist communities, especially of heterotrophic species, remain limited. In this review, we discuss the challenges associated with "field protistology", defined here as the exploration, characterization, and interpretation of microbial eukaryotic diversity within the context of natural environments or field experiments, and provide suggestions to help fill this important gap in knowledge. We also argue that increased efforts in field studies that combine molecular and microscopical methods offer the most promising path toward (1) the discovery of new lineages that expand the tree of eukaryotes; (2) the recognition of novel evolutionary patterns and processes; (3) the untangling of ecological interactions and functions, and their roles in larger ecosystem processes; and (4) the evaluation of protist adaptations to a changing climate. © 2013 The Author(s) Journal of Eukaryotic Microbiology © 2013 International Society of Protistologists.

  20. Cultural Evolutionary Perspectives on Creativity and Human Innovation.

    PubMed

    Fogarty, Laurel; Creanza, Nicole; Feldman, Marcus W

    2015-12-01

    Cultural traits originate through creative or innovative processes, which might be crucial to understanding how culture evolves and accumulates. However, because of its complexity and apparent subjectivity, creativity has remained largely unexplored as the dynamic underpinning of cultural evolution. Here, we explore the approach to innovation commonly taken in theoretical studies of cultural evolution and discuss its limitations. Drawing insights from cognitive science, psychology, archeology, and even animal behavior, it is possible to generate a formal description of creativity and to incorporate a dynamic theory of creativity into models of cultural evolution. We discuss the implications of such models for our understanding of the archaeological record and the history of hominid culture. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Molecular microenvironments: Solvent interactions with nucleic acid bases and ions

    NASA Technical Reports Server (NTRS)

    Macelroy, R. D.; Pohorille, A.

    1986-01-01

    The possibility of reconstructing plausible sequences of events in prebiotic molecular evolution is limited by the lack of fossil remains. However, with hindsight, one goal of molecular evolution was obvious: the development of molecular systems that became constituents of living systems. By understanding the interactions among molecules that are likely to have been present in the prebiotic environment, and that could have served as components in protobiotic molecular systems, plausible evolutionary sequences can be suggested. When stable aggregations of molecules form, a net decrease in free energy is observed in the system. Such changes occur when solvent molecules interact among themselves, as well as when they interact with organic species. A significant decrease in free energy, in systems of solvent and organic molecules, is due to entropy changes in the solvent. Entropy-driven interactioins played a major role in the organization of prebiotic systems, and understanding the energetics of them is essential to understanding molecular evolution.

  2. Human Microbiome and HIV/AIDS

    PubMed Central

    Li, Yihong; Yang, Liying; Pei, Zhiheng; Poles, Michael; Abrams, William R.; Malamud, Daniel

    2013-01-01

    Understanding of the human microbiome continues to grow rapidly; however, reports on changes in the microbiome after HIV infection are still limited. This review surveys the progress made in methodology associated with microbiome studies and highlights the remaining challenges to this field. Studies have shown that commensal oral, gut, vaginal, and penile bacteria are vital to the health of the human immune system. Our studies on crosstalk among oral and gastrointestinal soluble innate factors, HIV, and microbes indicated that the oral and gut microbiome was altered in the HIV-positive samples compared to the negative controls. The importance of understanding the bacterial component of HIV/AIDS, and likelihood of “crosstalk” between viral and bacterial pathogens, will help in understanding the role of the microbiome in HIV-infected individuals and facilitate identification of novel antiretroviral factors for use as novel diagnostics, microbicides, or therapeutics against HIV infection. PMID:22193889

  3. Machismo and Mexican American men: an empirical understanding using a gay sample.

    PubMed

    Estrada, Fernando; Rigali-Oiler, Marybeth; Arciniega, G Miguel; Tracey, Terence J G

    2011-07-01

    Machismo continues to be a defining aspect of Mexican American men that informs a wide array of psychological and behavioral dimensions. Although strides have been made in this area of research, understanding of the role of this construct in the lives of gay men remains incomplete. Our purpose in this study was to gain a deeper understanding of machismo using a sample of Mexican American gay men. This study examined for the first time whether a 2-factor model of machismo previously validated with heterosexual, Mexican American men generalized to a sample of 152 gay men of similar ethnic background. Relations between machismo, sexual risk, and internalized homophobia were also explored. Confirmatory factor analysis supported the 2-factor model with the current sample. Results also indicated machismo as predicting internalized homophobia and as an index of risky sex. Limitations are presented and implications are discussed.

  4. Marburg virus survivor immune responses are Th1 skewed with limited neutralizing antibody responses.

    PubMed

    Stonier, Spencer W; Herbert, Andrew S; Kuehne, Ana I; Sobarzo, Ariel; Habibulin, Polina; Dahan, Chen V Abramovitch; James, Rebekah M; Egesa, Moses; Cose, Stephen; Lutwama, Julius Julian; Lobel, Leslie; Dye, John M

    2017-09-04

    Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized. We report that immune responses in MARV survivors share characteristics with EBOV and SUDV infections but have some distinct differences. MARV survivors developed multivariate CD4 + T cell responses but limited CD8 + T cell responses, more in keeping with SUDV survivors than EBOV survivors. In stark contrast to SUDV survivors, rare neutralizing antibody responses in MARV survivors diminished rapidly after the outbreak. These results warrant serious consideration for any vaccine or therapeutic that seeks to be broadly protective, as different filoviruses may require different immune responses to achieve immunity. © 2017 Stonier et al.

  5. Pediatric anesthesia in developing countries.

    PubMed

    Bösenberg, Adrian T

    2007-06-01

    To highlight the problems faced in developing countries where healthcare resources are limited, with particular emphasis on pediatric anesthesia. The fact that very few publications address pediatric anesthesia in the developing world is not surprising given that most anesthetics are provided by nonphysicians, nurses or unqualified personnel. In compiling this article information is drawn from pediatric surgical, anesthetic and related texts. In a recent survey more than 80% of anesthesia providers in a poor country acknowledged that with the limited resources available they could not provide basic anesthesia for children less than 5 years. Although many publications could be regarded as anecdotal, the similarities to this survey suggest that the lack of facilities is more generalized than we would like to believe. The real risk of anesthesia in comparison to other major health risks such as human immunodeficiency virus, malaria, tuberculosis and trauma remains undetermined. The critical shortage of manpower remains a barrier to progress. Despite erratic electrical supplies, inconsistent oxygen delivery, paucity of drugs or equipment and on occasion even lack of running water, many provide life-saving anesthesia. Perioperative morbidity and mortality is, however, understandably high by developed world standards.

  6. Visual development in primates: Neural mechanisms and critical periods

    PubMed Central

    Kiorpes, Lynne

    2015-01-01

    Despite many decades of research into the development of visual cortex, it remains unclear what neural processes set limitations on the development of visual function and define its vulnerability to abnormal visual experience. This selected review examines the development of visual function and its neural correlates, and highlights the fact that in most cases receptive field properties of infant neurons are substantially more mature than infant visual function. One exception is temporal resolution, which can be accounted for by resolution of neurons at the level of the LGN. In terms of spatial vision, properties of single neurons alone are not sufficient to account for visual development. Different visual functions develop over different time courses. Their onset may be limited by the existence of neural response properties that support a given perceptual ability, but the subsequent time course of maturation to adult levels remains unexplained. Several examples are offered suggesting that taking account of weak signaling by infant neurons, correlated firing, and pooled responses of populations of neurons brings us closer to an understanding of the relationship between neural and behavioral development. PMID:25649764

  7. Atrial fibrillation driver mechanisms: Insight from the isolated human heart.

    PubMed

    Csepe, Thomas A; Hansen, Brian J; Fedorov, Vadim V

    2017-01-01

    Although there have been great technological advances in the treatment of atrial fibrillation (AF), current therapies remain limited due to a narrow understanding of AF mechanisms in the human heart. This review will highlight our recent studies on explanted human hearts where we developed and employed a novel functional-structural mapping approach by integrating high-resolution simultaneous endo-epicardial and panoramic optical mapping with 3D gadolinium-enhanced MRI to define the spatiotemporal characteristics of AF drivers and their structural substrates. The results allow us to postulate that the primary mechanism of AF maintenance in human hearts is a limited number of localized intramural microanatomic reentrant AF drivers anchored to heart-specific 3D fibrotically insulated myobundle tracks, which may remain hidden to clinical single-surface electrode mapping. We suggest that ex vivo human heart studies, by using an integrated 3D functional and structural mapping approach, will help to reveal defining features of AF drivers as well as validate and improve clinical approaches to detect and target these AF drivers in patients with cardiac diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Current State of Animal (Mouse) Modeling in Melanoma Research.

    PubMed

    Kuzu, Omer F; Nguyen, Felix D; Noory, Mohammad A; Sharma, Arati

    2015-01-01

    Despite the considerable progress in understanding the biology of human cancer and technological advancement in drug discovery, treatment failure remains an inevitable outcome for most cancer patients with advanced diseases, including melanoma. Despite FDA-approved BRAF-targeted therapies for advanced stage melanoma showed a great deal of promise, development of rapid resistance limits the success. Hence, the overall success rate of melanoma therapy still remains to be one of the worst compared to other malignancies. Advancement of next-generation sequencing technology allowed better identification of alterations that trigger melanoma development. As development of successful therapies strongly depends on clinically relevant preclinical models, together with the new findings, more advanced melanoma models have been generated. In this article, besides traditional mouse models of melanoma, we will discuss recent ones, such as patient-derived tumor xenografts, topically inducible BRAF mouse model and RCAS/TVA-based model, and their advantages as well as limitations. Although mouse models of melanoma are often criticized as poor predictors of whether an experimental drug would be an effective treatment, development of new and more relevant models could circumvent this problem in the near future.

  9. Mechanistic insights for the development of Li-O2 battery materials: addressing Li2O2 conductivity limitations and electrolyte and cathode instabilities.

    PubMed

    McCloskey, Bryan D; Burke, Colin M; Nichols, Jessica E; Renfrew, Sara E

    2015-08-18

    The Li-air battery has received significant attention over the past decade given its high theoretical specific energy compared to competing energy storage technologies. Yet, numerous scientific challenges remain unsolved in the pursuit of attaining a battery with modest Coulombic efficiency and high capacity. In this Feature Article, we provide our current perspective on challenges facing the development of nonaqueous Li-O2 battery cathodes. We initially present a review on our understanding of electrochemical processes occurring at the nonaqueous Li-O2 cathode. Electrolyte and cathode instabilities and Li2O2 conductivity limitations are then discussed, and suggestions for future materials research development to alleviate these issues are provided.

  10. Probing the limits of metal plasticity with molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Zepeda-Ruiz, Luis A.; Stukowski, Alexander; Oppelstrup, Tomas; Bulatov, Vasily V.

    2017-10-01

    Ordinarily, the strength and plasticity properties of a metal are defined by dislocations--line defects in the crystal lattice whose motion results in material slippage along lattice planes. Dislocation dynamics models are usually used as mesoscale proxies for true atomistic dynamics, which are computationally expensive to perform routinely. However, atomistic simulations accurately capture every possible mechanism of material response, resolving every ``jiggle and wiggle'' of atomic motion, whereas dislocation dynamics models do not. Here we present fully dynamic atomistic simulations of bulk single-crystal plasticity in the body-centred-cubic metal tantalum. Our goal is to quantify the conditions under which the limits of dislocation-mediated plasticity are reached and to understand what happens to the metal beyond any such limit. In our simulations, the metal is compressed at ultrahigh strain rates along its [001] crystal axis under conditions of constant pressure, temperature and strain rate. To address the complexity of crystal plasticity processes on the length scales (85-340 nm) and timescales (1 ns-1μs) that we examine, we use recently developed methods of in situ computational microscopy to recast the enormous amount of transient trajectory data generated in our simulations into a form that can be analysed by a human. Our simulations predict that, on reaching certain limiting conditions of strain, dislocations alone can no longer relieve mechanical loads; instead, another mechanism, known as deformation twinning (the sudden re-orientation of the crystal lattice), takes over as the dominant mode of dynamic response. Below this limit, the metal assumes a strain-path-independent steady state of plastic flow in which the flow stress and the dislocation density remain constant as long as the conditions of straining thereafter remain unchanged. In this distinct state, tantalum flows like a viscous fluid while retaining its crystal lattice and remaining a strong and stiff metal.

  11. Geometrically unrestricted, topologically constrained control of liquid crystal defects using simultaneous holonomic magnetic and holographic optical manipulation.

    PubMed

    Varney, Michael C M; Jenness, Nathan J; Smalyukh, Ivan I

    2014-02-01

    Despite the recent progress in physical control and manipulation of various condensed matter, atomic, and particle systems, including individual atoms and photons, our ability to control topological defects remains limited. Recently, controlled generation, spatial translation, and stretching of topological point and line defects have been achieved using laser tweezers and liquid crystals as model defect-hosting systems. However, many modes of manipulation remain hindered by limitations inherent to optical trapping. To overcome some of these limitations, we integrate holographic optical tweezers with a magnetic manipulation system, which enables fully holonomic manipulation of defects by means of optically and magnetically controllable colloids used as "handles" to transfer forces and torques to various liquid crystal defects. These colloidal handles are magnetically rotated around determined axes and are optically translated along three-dimensional pathways while mechanically attached to defects, which, combined with inducing spatially localized nematic-isotropic phase transitions, allow for geometrically unrestricted control of defects, including previously unrealized modes of noncontact manipulation, such as the twisting of disclination clusters. These manipulation capabilities may allow for probing topological constraints and the nature of defects in unprecedented ways, providing the foundation for a tabletop laboratory to expand our understanding of the role defects play in fields ranging from subatomic particle physics to early-universe cosmology.

  12. An osteoconductive, osteoinductive, and osteogenic tissue-engineered product for trauma and orthopaedic surgery: how far are we?

    PubMed

    Khan, Wasim S; Rayan, Faizal; Dhinsa, Baljinder S; Marsh, David

    2012-01-01

    The management of large bone defects due to trauma, degenerative disease, congenital deformities, and tumor resection remains a complex issue for the orthopaedic reconstructive surgeons. The requirement is for an ideal bone replacement which is osteoconductive, osteoinductive, and osteogenic. Autologous bone grafts are still considered the gold standard for reconstruction of bone defects, but donor site morbidity and size limitations are major concern. The use of bioartificial bone tissues may help to overcome these problems. The reconstruction of large volume defects remains a challenge despite the success of reconstruction of small-to-moderate-sized bone defects using engineered bone tissues. The aim of this paper is to understand the principles of tissue engineering of bone and its clinical applications in reconstructive surgery.

  13. An Osteoconductive, Osteoinductive, and Osteogenic Tissue-Engineered Product for Trauma and Orthopaedic Surgery: How Far Are We?

    PubMed Central

    Khan, Wasim S.; Rayan, Faizal; Dhinsa, Baljinder S.; Marsh, David

    2012-01-01

    The management of large bone defects due to trauma, degenerative disease, congenital deformities, and tumor resection remains a complex issue for the orthopaedic reconstructive surgeons. The requirement is for an ideal bone replacement which is osteoconductive, osteoinductive, and osteogenic. Autologous bone grafts are still considered the gold standard for reconstruction of bone defects, but donor site morbidity and size limitations are major concern. The use of bioartificial bone tissues may help to overcome these problems. The reconstruction of large volume defects remains a challenge despite the success of reconstruction of small-to-moderate-sized bone defects using engineered bone tissues. The aim of this paper is to understand the principles of tissue engineering of bone and its clinical applications in reconstructive surgery. PMID:25098363

  14. Pesticides reduce regional biodiversity of stream invertebrates

    PubMed Central

    Beketov, Mikhail A.; Kefford, Ben J.; Schäfer, Ralf B.; Liess, Matthias

    2013-01-01

    The biodiversity crisis is one of the greatest challenges facing humanity, but our understanding of the drivers remains limited. Thus, after decades of studies and regulation efforts, it remains unknown whether to what degree and at what concentrations modern agricultural pesticides cause regional-scale species losses. We analyzed the effects of pesticides on the regional taxa richness of stream invertebrates in Europe (Germany and France) and Australia (southern Victoria). Pesticides caused statistically significant effects on both the species and family richness in both regions, with losses in taxa up to 42% of the recorded taxonomic pools. Furthermore, the effects in Europe were detected at concentrations that current legislation considers environmentally protective. Thus, the current ecological risk assessment of pesticides falls short of protecting biodiversity, and new approaches linking ecology and ecotoxicology are needed. PMID:23776226

  15. Rendering LGBTQ+ Visible in Nursing: Embodying the Philosophy of Caring Science.

    PubMed

    Goldberg, Lisa; Rosenburg, Neal; Watson, Jean

    2017-06-01

    Although health care institutions continue to address the importance of diversity initiatives, the standard(s) for treatment remain historically and institutionally grounded in a sociocultural privileging of heterosexuality. As a result, lesbian, gay, bisexual, transgender, and queer (LGBTQ+) communities in health care remain largely invisible. This marked invisibility serves as a call to action, a renaissance of thinking within redefined boundaries and limitations. We must therefore refocus our habits of attention on the wholeness of persons and the diversity of their storied experiences as embodied through contemporary society. By rethinking current understandings of LGBTQ+ identities through innovative representation(s) of the media, music industry, and pop culture within a caring science philosophy, nurses have a transformative opportunity to render LGBTQ+ visible and in turn render a transformative opportunity for themselves.

  16. Empowerment in the field of health promotion: recognizing challenges in working toward equity.

    PubMed

    Berry, Nicole S; Murphy, Jill; Coser, Larissa

    2014-12-01

    Over the last 25 years, the language of empowerment has been woven into the guiding missions and descriptions of institutions, funding and projects globally. Although theoretical understandings of empowerment within the domain of health promotion remain contentious, we have little idea of how a shift toward an empowerment agenda has affected the daily work of those in the field of health promotion. A systematic examination of the implementation of the empowerment agenda is important as it can help us understand how redistributive agendas are received within the multiple institutional contexts in which health promotion work is carried out. The goal of this study, therefore, was to try to understand the empowerment agenda within the context of everyday health promotion. We conducted semi-structured interviews with health promoters from a variety of geographical regions, institutional backgrounds, and job capacities. Essentially we found that empowerment remains conceptually dear to health promoters' understanding of their work, yet at the same time, mainstreaming empowerment is at odds with central trends and initiatives that govern this work. We argue that many of the stumbling blocks that have hindered this specific agenda are actually central stumbling blocks for the wider field of health promotion. We examine some of the barriers to implementing transformational change. Overcoming the primary limitations uncovered in this exploration of empowerment is actually crucial to progressive work in health promotion in general, particularly work that would seek to lessen inequities. © The Author(s) 2014.

  17. Adult Children's Education and Parents' Functional Limitations in Mexico.

    PubMed

    Yahirun, Jenjira J; Sheehan, Connor M; Hayward, Mark D

    2016-04-01

    This article asks how adult children's education influences older parents' physical health in Mexico, a context where older adults often lack access to institutional resources and rely on kin, primarily children, as a main source of support. Using logistic and negative binomial regression models and data from the first wave of the Mexican Health and Aging Study (N = 9,661), we find that parents whose children all completed high school are less likely to report any functional limitations as well as fewer limitations compared to parents with no children who completed high school. This association remains significant even after accounting for parent and offspring-level characteristics, including parents' income that accounts for children's financial transfers to parents. Future research should aim to understand the mechanisms that explain the association between adult children's education and changes to parents' health over time. © The Author(s) 2015.

  18. Adult Children’s Education and Parents’ Functional Limitations in Mexico

    PubMed Central

    Yahirun, Jenjira J.; Sheehan, Connor M.; Hayward, Mark D.

    2016-01-01

    This article asks how adult children’s education influences older parents’ physical health in Mexico, a context where older adults often lack access to institutional resources and rely on kin, primarily children, as a main source of support. Using logistic and negative binomial regression models and data from the first wave of the Mexican Health and Aging Study (N = 9,661), we find that parents whose children all completed high school are less likely to report any functional limitations as well as fewer limitations compared to parents with no children who completed high school. This association remains significant even after accounting for parent and offspring-level characteristics, including parents’ income that accounts for children’s financial transfers to parents. Future research should aim to understand the mechanisms that explain the association between adult children’s education and changes to parents’ health over time. PMID:26966254

  19. Exploring Ultimate Water Capillary Evaporation in Nanoscale Conduits.

    PubMed

    Li, Yinxiao; Alibakhshi, Mohammad Amin; Zhao, Yihong; Duan, Chuanhua

    2017-08-09

    Capillary evaporation in nanoscale conduits is an efficient heat/mass transfer strategy that has been widely utilized by both nature and mankind. Despite its broad impact, the ultimate transport limits of capillary evaporation in nanoscale conduits, governed by the evaporation/condensation kinetics at the liquid-vapor interface, have remained poorly understood. Here we report experimental study of the kinetic limits of water capillary evaporation in two dimensional nanochannels using a novel hybrid channel design. Our results show that the kinetic-limited evaporation fluxes break down the limits predicated by the classical Hertz-Knudsen equation by an order of magnitude, reaching values up to 37.5 mm/s with corresponding heat fluxes up to 8500 W/cm 2 . The measured evaporation flux increases with decreasing channel height and relative humidity but decreases as the channel temperature decreases. Our findings have implications for further understanding evaporation at the nanoscale and developing capillary evaporation-based technologies for both energy- and bio-related applications.

  20. Climatic correlates of tree mortality in water- and energy-limited forests

    USGS Publications Warehouse

    Das, Adrian J.; Stephenson, Nathan L.; Flint, Alan; Das, Tapash; van Mantgem, Phillip J.

    2013-01-01

    Recent increases in tree mortality rates across the western USA are correlated with increasing temperatures, but mechanisms remain unresolved. Specifically, increasing mortality could predominantly be a consequence of temperature-induced increases in either (1) drought stress, or (2) the effectiveness of tree-killing insects and pathogens. Using long-term data from California’s Sierra Nevada mountain range, we found that in water-limited (low-elevation) forests mortality was unambiguously best modeled by climatic water deficit, consistent with the first mechanism. In energy-limited (high-elevation) forests deficit models were only equivocally better than temperature models, suggesting that the second mechanism is increasingly important in these forests. We could not distinguish between models predicting mortality using absolute versus relative changes in water deficit, and these two model types led to different forecasts of mortality vulnerability under future climate scenarios. Our results provide evidence for differing climatic controls of tree mortality in water- and energy-limited forests, while highlighting the need for an improved understanding of tree mortality processes.

  1. Climatic correlates of tree mortality in water- and energy-limited forests.

    PubMed

    Das, Adrian J; Stephenson, Nathan L; Flint, Alan; Das, Tapash; van Mantgem, Phillip J

    2013-01-01

    Recent increases in tree mortality rates across the western USA are correlated with increasing temperatures, but mechanisms remain unresolved. Specifically, increasing mortality could predominantly be a consequence of temperature-induced increases in either (1) drought stress, or (2) the effectiveness of tree-killing insects and pathogens. Using long-term data from California's Sierra Nevada mountain range, we found that in water-limited (low-elevation) forests mortality was unambiguously best modeled by climatic water deficit, consistent with the first mechanism. In energy-limited (high-elevation) forests deficit models were only equivocally better than temperature models, suggesting that the second mechanism is increasingly important in these forests. We could not distinguish between models predicting mortality using absolute versus relative changes in water deficit, and these two model types led to different forecasts of mortality vulnerability under future climate scenarios. Our results provide evidence for differing climatic controls of tree mortality in water- and energy-limited forests, while highlighting the need for an improved understanding of tree mortality processes.

  2. Understanding of polyhydroxybutyrate production under carbon and phosphorus-limited growth conditions in non-axenic continuous culture.

    PubMed

    Cavaillé, Laëtitia; Albuquerque, Maria; Grousseau, Estelle; Lepeuple, Anne-Sophie; Uribelarrea, Jean-Louis; Hernandez-Raquet, Guillermina; Paul, Etienne

    2016-02-01

    In a waste into resource strategy, a selection of polyhydroxybutyrate (PHB)-accumulating organisms from activated sludge was achieved in an open continuous culture under acetic acid and phosphorus limitation. Once the microbial population was selected at a dilution rate (D), an increase in phosphorus limitation degree was applied in order to study the intracellular phosphorus plasticity of selected bacteria and the resulting capacity to produce PHB. Whatever D, all selected populations were able to produce PHB. At a D, the phosphorus availability determined the phosphorus-cell content which in turn fixed the amount of cell. All the remaining carbon was thus directed toward PHB. By decreasing D, microorganisms adapted more easily to higher phosphorus limitation leading to higher PHB content. A one-stage continuous reactor operated at D=0.023h(-)(1) gave reliable high PHB productivity with PHB content up to 80%. A two-stage reactor could ensure better productivity while allowing tuning product quality. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Climatic Correlates of Tree Mortality in Water- and Energy-Limited Forests

    PubMed Central

    Das, Adrian J.; Stephenson, Nathan L.; Flint, Alan; Das, Tapash; van Mantgem, Phillip J.

    2013-01-01

    Recent increases in tree mortality rates across the western USA are correlated with increasing temperatures, but mechanisms remain unresolved. Specifically, increasing mortality could predominantly be a consequence of temperature-induced increases in either (1) drought stress, or (2) the effectiveness of tree-killing insects and pathogens. Using long-term data from California’s Sierra Nevada mountain range, we found that in water-limited (low-elevation) forests mortality was unambiguously best modeled by climatic water deficit, consistent with the first mechanism. In energy-limited (high-elevation) forests deficit models were only equivocally better than temperature models, suggesting that the second mechanism is increasingly important in these forests. We could not distinguish between models predicting mortality using absolute versus relative changes in water deficit, and these two model types led to different forecasts of mortality vulnerability under future climate scenarios. Our results provide evidence for differing climatic controls of tree mortality in water- and energy-limited forests, while highlighting the need for an improved understanding of tree mortality processes. PMID:23936118

  4. Understanding heart rate alarm adjustment in the intensive care units through an analytical approach

    PubMed Central

    Pelter, Michele M.; Drew, Barbara J.; Palacios, Jorge Arroyo; Bai, Yong; Stannard, Daphne; Aldrich, J. Matt; Hu, Xiao

    2017-01-01

    Background Heart rate (HR) alarms are prevalent in ICU, and these parameters are configurable. Not much is known about nursing behavior associated with tailoring HR alarm parameters to individual patients to reduce clinical alarm fatigue. Objectives To understand the relationship between heart rate (HR) alarms and adjustments to reduce unnecessary heart rate alarms. Methods Retrospective, quantitative analysis of an adjudicated database using analytical approaches to understand behaviors surrounding parameter HR alarm adjustments. Patients were sampled from five adult ICUs (77 beds) over one month at a quaternary care university medical center. A total of 337 of 461 ICU patients had HR alarms with 53.7% male, mean age 60.3 years, and 39% non-Caucasian. Default HR alarm parameters were 50 and 130 beats per minute (bpm). The occurrence of each alarm, vital signs, and physiologic waveforms was stored in a relational database (SQL server). Results There were 23,624 HR alarms for analysis, with 65.4% exceeding the upper heart rate limit. Only 51% of patients with HR alarms had parameters adjusted, with a median upper limit change of +5 bpm and -1 bpm lower limit. The median time to first HR parameter adjustment was 17.9 hours, without reduction in alarms occurrence (p = 0.57). Conclusions HR alarms are prevalent in ICU, and half of HR alarm settings remain at default. There is a long delay between HR alarms and parameters changes, with insufficient changes to decrease HR alarms. Increasing frequency of HR alarms shortens the time to first adjustment. Best practice guidelines for HR alarm limits are needed to reduce alarm fatigue and improve monitoring precision. PMID:29176776

  5. Earliest Archaeological Evidence of Persistent Hominin Carnivory

    PubMed Central

    Ferraro, Joseph V.; Plummer, Thomas W.; Pobiner, Briana L.; Oliver, James S.; Bishop, Laura C.; Braun, David R.; Ditchfield, Peter W.; Seaman, John W.; Binetti, Katie M.; Seaman, John W.; Hertel, Fritz; Potts, Richard

    2013-01-01

    The emergence of lithic technology by ∼2.6 million years ago (Ma) is often interpreted as a correlate of increasingly recurrent hominin acquisition and consumption of animal remains. Associated faunal evidence, however, is poorly preserved prior to ∼1.8 Ma, limiting our understanding of early archaeological (Oldowan) hominin carnivory. Here, we detail three large well-preserved zooarchaeological assemblages from Kanjera South, Kenya. The assemblages date to ∼2.0 Ma, pre-dating all previously published archaeofaunas of appreciable size. At Kanjera, there is clear evidence that Oldowan hominins acquired and processed numerous, relatively complete, small ungulate carcasses. Moreover, they had at least occasional access to the fleshed remains of larger, wildebeest-sized animals. The overall record of hominin activities is consistent through the stratified sequence – spanning hundreds to thousands of years – and provides the earliest archaeological evidence of sustained hominin involvement with fleshed animal remains (i.e., persistent carnivory), a foraging adaptation central to many models of hominin evolution. PMID:23637995

  6. Adverse Childhood Experiences and Higher-Level Functional Limitations Among Older Japanese People: Results From the JAGES Study.

    PubMed

    Amemiya, Airi; Fujiwara, Takeo; Murayama, Hiroshi; Tani, Yukako; Kondo, Katsunori

    2018-01-16

    A life-course perspective is essential in understanding the determinants of higher-level functional limitations. We examine the impact of adverse childhood experiences (ACEs) on higher-level functional limitations in older people. Data were from the Japan Gerontological Evaluation Study 2013, a population-based cohort of independent people aged 65 years or older across Japan (n = 19,220). ACEs before the age of 18 were assessed in terms of seven adversities: parental death, parental divorce, parental mental illness, family violence, physical abuse, psychological neglect, and psychological abuse. Associations between the cumulative number of ACEs and higher-level functional limitations were investigated by multivariate Poisson regression with robust error variances, adjusted for age, gender, childhood disadvantage, adult sociodemographics, adult health behaviors, and health status. Of the older people, 36.3% reported at least one ACE. Older people who had experienced two or more ACEs showed significantly greater higher-level functional limitations than those with no ACE in a crude model (prevalence ratio, PR = 1.61, 95% confidence interval, CI = 1.51-1.71). After adjusting the covariates, this association remained (PR = 1.19, 95% CI = 1.12-1.27). ACEs showed robust independent effects on higher-level functional limitations among older Japanese without disabilities, even after adjusting for potential covariates in childhood and adulthood. The current findings may help in understanding the impact of the latent effects of ACEs on functional limitations in older people. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. The OncoPPi Portal: an integrative resource to explore and prioritize protein-protein interactions for cancer target discovery. | Office of Cancer Genomics

    Cancer.gov

    Motivation: As cancer genomics initiatives move toward comprehensive identification of genetic alterations in cancer, attention is now turning to understanding how interactions among these genes lead to the acquisition of tumor hallmarks. Emerging pharmacological and clinical data suggest a highly promising role of cancer-specific protein-protein interactions (PPIs) as druggable cancer targets. However, large-scale experimental identification of cancer-related PPIs remains challenging, and currently available resources to explore oncogenic PPI networks are limited.

  8. An acceptable role for computers in the aircraft design process

    NASA Technical Reports Server (NTRS)

    Gregory, T. J.; Roberts, L.

    1980-01-01

    Some of the reasons why the computerization trend is not wholly accepted are explored for two typical cases: computer use in the technical specialties and computer use in aircraft synthesis. The factors that limit acceptance are traced in part, to the large resources needed to understand the details of computer programs, the inability to include measured data as input to many of the theoretical programs, and the presentation of final results without supporting intermediate answers. Other factors are due solely to technical issues such as limited detail in aircraft synthesis and major simplifying assumptions in the technical specialties. These factors and others can be influenced by the technical specialist and aircraft designer. Some of these factors may become less significant as the computerization process evolves, but some issues, such as understanding large integrated systems, may remain issues in the future. Suggestions for improved acceptance include publishing computer programs so that they may be reviewed, edited, and read. Other mechanisms include extensive modularization of programs and ways to include measured information as part of the input to theoretical approaches.

  9. Childhood Brain Tumor Epidemiology: A Brain Tumor Epidemiology Consortium Review

    PubMed Central

    Johnson, Kimberly J.; Cullen, Jennifer; Barnholtz-Sloan, Jill S.; Ostrom, Quinn T.; Langer, Chelsea E.; Turner, Michelle C.; McKean-Cowdin, Roberta; Fisher, James L.; Lupo, Philip J.; Partap, Sonia; Schwartzbaum, Judith A.; Scheurer, Michael E.

    2014-01-01

    Childhood brain tumors are the most common pediatric solid tumor and include several histological subtypes. Although progress has been made in improving survival rates for some subtypes, understanding of risk factors for childhood brain tumors remains limited to a few genetic syndromes and ionizing radiation to the head and neck. In this report, we review descriptive and analytical epidemiology childhood brain tumor studies from the past decade and highlight priority areas for future epidemiology investigations and methodological work that is needed to advance our understanding of childhood brain tumor causes. Specifically, we summarize the results of a review of studies published since 2004 that have analyzed incidence and survival in different international regions and that have examined potential genetic, immune system, developmental and birth characteristics, and environmental risk factors. PMID:25192704

  10. A chronicle of a killer alga in the west: ecology, assessment, and management of Prymnesium parvum blooms

    USGS Publications Warehouse

    Roelke, D.L.; Barkoh, Aaron; Brooks, B.W.; Grover, J.P.; Hambright, K.D.; LaClaire, John W.; Moeller, Peter D.R.; Patino, Reynaldo

    2015-01-01

    Since the mid-1980s, fish-killing blooms ofPrymnesium parvum spread throughout the USA. In the south central USA, P. parvum blooms have commonly spanned hundreds of kilometers. There is much evidence that physiological stress brought on by inorganic nutrient limitation enhances toxicity. Other factors influence toxin production as well, such as stress experienced at low salinity and temperature. A better understanding of toxin production by P. parvum remains elusive and the identities and functions of chemicals produced are unclear. This limits our understanding of factors that facilitated the spread of P. parvum blooms. In the south central USA, not only is there evidence that the spread of blooms was controlled, in part, by migration limitation. But there are also observations that suggest changed environmental conditions, primarily salinity, facilitated the spread of blooms. Other factors that might have played a role include altered hydrology and nutrient loading. Changes in water hardness, herbicide use, system pH, and the presence of toxin-resistant and/or P. parvum-inhibiting plankton may also have played a role. Management of P. parvum in natural systems has yet to be attempted, but may be guided by successes achieved in small impoundments and mesocosm experiments that employed various chemical and hydraulic control approaches.

  11. Harnessing Host-Vector Microbiome for Sustainable Plant Disease Management of Phloem-Limited Bacteria

    PubMed Central

    Trivedi, Pankaj; Trivedi, Chanda; Grinyer, Jasmine; Anderson, Ian C.; Singh, Brajesh K.

    2016-01-01

    Plant health and productivity is strongly influenced by their intimate interaction with deleterious and beneficial organisms, including microbes, and insects. Of the various plant diseases, insect-vectored diseases are of particular interest, including those caused by obligate parasites affecting plant phloem such as Candidatus (Ca.) Phytoplasma species and several species of Ca. Liberibacter. Recent studies on plant–microbe and plant–insect interactions of these pathogens have demonstrated that plant–microbe–insect interactions have far reaching consequences for the functioning and evolution of the organisms involved. These interactions take place within complex pathosystems and are shaped by a myriad of biotic and abiotic factors. However, our current understanding of these processes and their implications for the establishment and spread of insect-borne diseases remains limited. This article highlights the molecular, ecological, and evolutionary aspects of interactions among insects, plants, and their associated microbial communities with a focus on insect vectored and phloem-limited pathogens belonging to Ca. Phytoplasma and Ca. Liberibacter species. We propose that innovative and interdisciplinary research aimed at linking scales from the cellular to the community level will be vital for increasing our understanding of the mechanisms underpinning plant–insect–microbe interactions. Examination of such interactions could lead us to applied solutions for sustainable disease and pest management. PMID:27746788

  12. Harnessing Host-Vector Microbiome for Sustainable Plant Disease Management of Phloem-Limited Bacteria.

    PubMed

    Trivedi, Pankaj; Trivedi, Chanda; Grinyer, Jasmine; Anderson, Ian C; Singh, Brajesh K

    2016-01-01

    Plant health and productivity is strongly influenced by their intimate interaction with deleterious and beneficial organisms, including microbes, and insects. Of the various plant diseases, insect-vectored diseases are of particular interest, including those caused by obligate parasites affecting plant phloem such as Candidatus ( Ca .) Phytoplasma species and several species of Ca. Liberibacter. Recent studies on plant-microbe and plant-insect interactions of these pathogens have demonstrated that plant-microbe-insect interactions have far reaching consequences for the functioning and evolution of the organisms involved. These interactions take place within complex pathosystems and are shaped by a myriad of biotic and abiotic factors. However, our current understanding of these processes and their implications for the establishment and spread of insect-borne diseases remains limited. This article highlights the molecular, ecological, and evolutionary aspects of interactions among insects, plants, and their associated microbial communities with a focus on insect vectored and phloem-limited pathogens belonging to Ca. Phytoplasma and Ca. Liberibacter species. We propose that innovative and interdisciplinary research aimed at linking scales from the cellular to the community level will be vital for increasing our understanding of the mechanisms underpinning plant-insect-microbe interactions. Examination of such interactions could lead us to applied solutions for sustainable disease and pest management.

  13. Capacity and precision in an animal model of visual short-term memory

    PubMed Central

    Lara, Antonio H.; Wallis, Jonathan D.

    2013-01-01

    Temporary storage of information in visual short-term memory (VSTM) is a key component of many complex cognitive abilities. However, it is highly limited in capacity. Understanding the neurophysiological nature of this capacity limit will require a valid animal model of VSTM. We used a multiple-item color change detection task to measure macaque monkeys’ VSTM capacity. Subjects’ performance deteriorated and reaction times increased as a function of the number of items in memory. Additionally, we measured the precision of the memory representations by varying the distance between sample and test colors. In trials with similar sample and test colors, subjects made more errors compared to trials with highly discriminable colors. We modeled the error distribution as a Gaussian function and used this to estimate the precision of VSTM representations. We found that as the number of items in memory increases the precision of the representations decreases dramatically. Additionally, we found that focusing attention on one of the objects increases the precision with which that object is stored and degrading the precision of the remaining. These results are in line with recent findings in human psychophysics and provide a solid foundation for understanding the neurophysiological nature of the capacity limit of VSTM. PMID:22419756

  14. Arthritis and employment: an examination of behavioral coping efforts to manage workplace activity limitations.

    PubMed

    Gignac, Monique A M

    2005-06-15

    To examine ways in which individuals with arthritis manage their employment and health by focusing on the type and determinants of diverse behavioral coping strategies used to manage activity limitations, and to examine the relationship between coping behaviors and participation in employment. The study group comprised 492 patients with osteoarthritis or rheumatoid arthritis. All participants were employed, and all participants were administered an in-depth, structured questionnaire. The study used an inductive approach and distinguished among 4 categories of coping behaviors as follows: adjustments to time spent on activities; receipt of help; modification of behaviors; and anticipatory coping. Fewer coping behaviors were reported at the workplace than outside of the workplace. Anticipatory coping was used most often in the workplace. Workplace activity limitations were related to increased reports of all types of coping. Women, those with more joints affected, and people expecting to remain employed reported more anticipatory coping. Expectations of continued employment were also related to modifications of activities, as was longer disease duration and discussing arthritis with one's employer. Help from others was associated with talking to an employer and positive job perceptions. Compared with work, reports of a greater number of coping behaviors used at home were associated with changes in overall work participation (e.g., absenteeism). These results expand our understanding of the experience of having a chronic illness and working and highlight the ways in which people accommodate to workplace limitations by using a variety of different behavioral coping efforts to remain employed.

  15. Connecting the coronaries: How the coronary plexus develops and is functionalized

    PubMed Central

    Dyer, Laura; Pi, Xinchun; Patterson, Cam

    2015-01-01

    The establishment of the coronary circulation is one of the final critical steps during heart development. Despite decades of research, our understanding of how the coronary vasculature develops and connects to the aorta remains limited. This review serves two specific purposes: it addresses recent advances in understanding the origin of the coronary endothelium, and it then focuses on the last crucial step of coronary vasculature development, the connection of the coronary plexus to the aorta. The chick and quail animal models have yielded most of the information for how these connections form, starting with a fine network of vessels that penetrate the aorta and coalesce to form two distinct ostia. Studies in mouse and rat confirm that at least some of these steps are conserved in mammals, but gaps still exist in our understanding of mammalian coronary ostia formation. The signaling cues necessary to guide the coronary plexus to the aorta are also incompletely understood. Hypoxia-inducible transcription factor-1 and its downstream targets are among the few identified genes that promote the formation of the coronary stems. Together, this review summarizes our current knowledge of coronary vascular formation and highlights the significant gaps that remain. In addition, it highlights some of the coronary artery anomalies known to affect human health, demonstrating that even seemingly subtle defects arising from incorrect coronary plexus formation can result in significant health crises. PMID:25173872

  16. 'Damn that's bright!' - why ignoring the Eddington limit is so much fun

    NASA Astrophysics Data System (ADS)

    Middleton, M.

    2017-10-01

    Decades of studying compact objects has led to an explosion in our understanding, yet some puzzles remain unanswered. Whilst the vast majority of Galactic black hole binary systems accrete at a rate below their classical Eddington limit, several appear to exceed it and whilst doing so show the most dramatic of phenomenology including the most powerful ballistic jet events and equatorial outflows. Standing alone as the most extreme example is the Galactic microquasar SS433. Long considered by some to be a Galactic `ultraluminous X-ray source', it is literally shrouded in mystery thanks to an optically thick wind obscuring the central regions. I will discuss these systems and new work which sheds light on SS433 and how it might fit into the growing picture of super-critically accreting sources.

  17. Do neural nets learn statistical laws behind natural language?

    PubMed

    Takahashi, Shuntaro; Tanaka-Ishii, Kumiko

    2017-01-01

    The performance of deep learning in natural language processing has been spectacular, but the reasons for this success remain unclear because of the inherent complexity of deep learning. This paper provides empirical evidence of its effectiveness and of a limitation of neural networks for language engineering. Precisely, we demonstrate that a neural language model based on long short-term memory (LSTM) effectively reproduces Zipf's law and Heaps' law, two representative statistical properties underlying natural language. We discuss the quality of reproducibility and the emergence of Zipf's law and Heaps' law as training progresses. We also point out that the neural language model has a limitation in reproducing long-range correlation, another statistical property of natural language. This understanding could provide a direction for improving the architectures of neural networks.

  18. Youth Acquisition of Alcohol and Drinking Contexts: An In-Depth Look

    PubMed Central

    Friese, Bettina; Grube, Joel W.; Moore, Roland S.

    2015-01-01

    Despite efforts to limit underage access to alcohol, alcohol availability remains a challenge for youth drinking prevention. This paper fills a gap in our understanding of alcohol consumption among youths by systematically investigating how and under what circumstances they obtain alcohol and the context within which they consume it. Qualitative interviews (n=47) were conducted with teens to collect information about where and how they obtain alcohol and the contexts within which they drink. Respondents were knowledgeable about commercial and social sources and used this knowledge in their decision making regarding where to obtain alcohol. Teens used their social relationships to circumvent existing policies designed to limit underage access to alcohol. Findings indicate that the majority of teens’ drinking occasions occur in their own or someone else’s home. PMID:25445811

  19. Do neural nets learn statistical laws behind natural language?

    PubMed Central

    Takahashi, Shuntaro

    2017-01-01

    The performance of deep learning in natural language processing has been spectacular, but the reasons for this success remain unclear because of the inherent complexity of deep learning. This paper provides empirical evidence of its effectiveness and of a limitation of neural networks for language engineering. Precisely, we demonstrate that a neural language model based on long short-term memory (LSTM) effectively reproduces Zipf’s law and Heaps’ law, two representative statistical properties underlying natural language. We discuss the quality of reproducibility and the emergence of Zipf’s law and Heaps’ law as training progresses. We also point out that the neural language model has a limitation in reproducing long-range correlation, another statistical property of natural language. This understanding could provide a direction for improving the architectures of neural networks. PMID:29287076

  20. Proinflammatory Stem Cell Signaling in Cardiac Ischemia

    PubMed Central

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

    2009-01-01

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

  1. Tsunami warnings: Understanding in Hawai'i

    USGS Publications Warehouse

    Gregg, Chris E.; Houghton, Bruce F.; Paton, Douglas; Johnston, David M.; Swanson, D.A.; Yanagi, B.S.

    2007-01-01

    The devastating southeast Asian tsunami of December 26, 2004 has brought home the destructive consequences of coastal hazards in an absence of effective warning systems. Since the 1946 tsunami that destroyed much of Hilo, Hawai'i, a network of pole mounted sirens has been used to provide an early public alert of future tsunamis. However, studies in the 1960s showed that understanding of the meaning of siren soundings was very low and that ambiguity in understanding had contributed to fatalities in the 1960 tsunami that again destroyed much of Hilo. The Hawaiian public has since been exposed to monthly tests of the sirens for more than 25 years and descriptions of the system have been widely published in telephone books for at least 45 years. However, currently there remains some uncertainty in the level of public understanding of the sirens and their implications for behavioral response. Here, we show from recent surveys of Hawai'i residents that awareness of the siren tests and test frequency is high, but these factors do not equate with increased understanding of the meaning of the siren, which remains disturbingly low (13%). Furthermore, the length of time people have lived in Hawai'i is not correlated systematically with understanding of the meaning of the sirens. An additional issue is that warning times for tsunamis gene rated locally in Hawai'i will be of the order of minutes to tens of minutes and limit the immediate utility of the sirens. Natural warning signs of such tsunamis may provide the earliest warning to residents. Analysis of a survey subgroup from Hilo suggests that awareness of natural signs is only moderate, and a majority may expect notification via alerts provided by official sources. We conclude that a major change is needed in tsunami education, even in Hawai'i, to increase public understanding of, and effective response to, both future official alerts and natural warning signs of future tsunamis. ?? Springer 2006.

  2. Mind the Gap: Current Challenges and Future State of Heart Failure Care.

    PubMed

    McDonald, Michael A; Ashley, Euan A; Fedak, Paul W M; Hawkins, Nathaniel; Januzzi, James L; McMurray, John J V; Parikh, Victoria N; Rao, Vivek; Svystonyuk, Daniyil; Teerlink, John R; Virani, Sean

    2017-11-01

    The past decade has seen many advances in the management of heart failure (HF) that have improved survival and quality of life for patients living with this condition. A number of gaps remain in our understanding of the pathophysiology of HF, and the application of emerging treatment strategies is an exciting but daunting challenge. It is possible that advances in genetic evaluation of cardiomyopathy will provide a more refined approach to characterizing HF syndromes, whereas large-scale clinical trials on the horizon should further clarify the role of novel pharmacologic agents and invasive therapies. Cardiac repair and regeneration hold great promise, but a number of pragmatic issues will limit clinical application in the near term. Replacing cardiac function with ventricular assist devices represents significant progress in the management of advanced disease; however, unacceptable rates of complications and costs need to be addressed before broader use in the general HF population is feasible. The ability to personalize care is limited, and the optimal model of disease management in the Canadian context remains uncertain. The emergence of biomarker-guided management and remote monitoring technologies might facilitate a more personalized approach to care in an effort to maintain health and stability and to prevent worsening HF. Ultimately, a greater understanding of how and when to intervene in the setting of acute HF should translate into improved outcomes for the highest-risk subgroup of patients. This review highlights key challenges in the management of HF and highlights the progress toward an ideal future state. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  3. High-resolution monitoring of stormwater quality in an urbanising catchment in the United Kingdom during the 2013/2014 winter storms

    NASA Astrophysics Data System (ADS)

    McGrane, S. J.; Hutchins, M. G.; Kjeldsen, T. R.; Miller, J. D.; Bussi, G.; Loewenthal, M.

    2015-12-01

    Urban areas are widely recognised as a key source of contaminants entering our freshwater systems, yet in spite of this, our understanding of stormwater quality dynamics remains limited. The development of in-situ, high-resolution monitoring equipment has revolutionised our capability to capture flow and water quality data at a sub-hourly resolution, enabling us to potentially enhance our understanding of hydrochemical variations from contrasting landscapes during storm events. During the winter of 2013/2014, the United Kingdom experienced a succession of intense storm events, where the south of the country experienced 200% of the average rainfall, resulting in widespread flooding across the Thames basin. We applied high-frequency (15 minute resolution) water quality monitoring across ten contrasting subcatchments (including rural, urban and mixed land-use catchments), seeking to classify the disparity in water quality conditions both within- and between events. Rural catchments increasingly behave like "urban" catchments as soils wet up and become increasingly responsive to subsequent events, however water quality response during the winter months remains limited. By contrast, increasingly urban catchments yield greater contaminant loads during events, and pre-event baseline chemistry highlights a resupply source in dense urban catchments. Wastewater treatment plants were shown to dominate baseline chemistry during low-flow events but also yield a considerable impact on stormwater outputs during peak-flow events, as hydraulic push results in the outflow of untreated solid wastes into the river system. Results are discussed in the context of water quality policy; urban growth scenarios and BMP for stormwater runoff in contrasting landscapes.

  4. Height Dependency of Aerosol-Cloud Interaction Regimes: Height Dependency of ACI Regime

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

    Chen, Jingyi; Liu, Yangang; Zhang, Minghua

    This study investigates the height dependency of aerosol-cloud interaction regimes in terms of the joint dependence of the key cloud microphysical properties (e.g. cloud droplet number concentration, cloud droplet relative dispersion, etc.) on aerosol number concentration (N a) and vertical velocity (w). The three distinct regimes with different microphysical features are the aerosol-limited regime, the updraft-limited regime, and the transitional regime. The results reveal two new phenomena in updraft-limited regime: 1) The “condensational broadening” of cloud droplet size distribution in contrast to the well-known “condensational narrowing” in the aerosol-limited regime; 2) Above the level of maximum supersaturation, some cloud dropletsmore » are deactivated into interstitial aerosols in the updraft-limited regime whereas all droplets remain activated in the aerosol-limited regime. Further analysis shows that the particle equilibrium supersaturation plays important role in understanding these unique features. Also examined is the height of warm rain initiation and its dependence on N a and w. The rain initiation height is found to depend primarily on either N a or w or both in different N a-w regimes, thus suggesting a strong regime dependence of the second aerosol indirect effect.« less

  5. Height Dependency of Aerosol-Cloud Interaction Regimes: Height Dependency of ACI Regime

    DOE PAGES

    Chen, Jingyi; Liu, Yangang; Zhang, Minghua; ...

    2018-01-10

    This study investigates the height dependency of aerosol-cloud interaction regimes in terms of the joint dependence of the key cloud microphysical properties (e.g. cloud droplet number concentration, cloud droplet relative dispersion, etc.) on aerosol number concentration (N a) and vertical velocity (w). The three distinct regimes with different microphysical features are the aerosol-limited regime, the updraft-limited regime, and the transitional regime. The results reveal two new phenomena in updraft-limited regime: 1) The “condensational broadening” of cloud droplet size distribution in contrast to the well-known “condensational narrowing” in the aerosol-limited regime; 2) Above the level of maximum supersaturation, some cloud dropletsmore » are deactivated into interstitial aerosols in the updraft-limited regime whereas all droplets remain activated in the aerosol-limited regime. Further analysis shows that the particle equilibrium supersaturation plays important role in understanding these unique features. Also examined is the height of warm rain initiation and its dependence on N a and w. The rain initiation height is found to depend primarily on either N a or w or both in different N a-w regimes, thus suggesting a strong regime dependence of the second aerosol indirect effect.« less

  6. Computational toxicology: Its essential role in reducing drug attrition.

    PubMed

    Naven, R T; Louise-May, S

    2015-12-01

    Predictive toxicology plays a critical role in reducing the failure rate of new drugs in pharmaceutical research and development. Despite recent gains in our understanding of drug-induced toxicity, however, it is urgent that the utility and limitations of our current predictive tools be determined in order to identify gaps in our understanding of mechanistic and chemical toxicology. Using recently published computational regression analyses of in vitro and in vivo toxicology data, it will be demonstrated that significant gaps remain in early safety screening paradigms. More strategic analyses of these data sets will allow for a better understanding of their domain of applicability and help identify those compounds that cause significant in vivo toxicity but which are currently mis-predicted by in silico and in vitro models. These 'outliers' and falsely predicted compounds are metaphorical lighthouses that shine light on existing toxicological knowledge gaps, and it is essential that these compounds are investigated if attrition is to be reduced significantly in the future. As such, the modern computational toxicologist is more productively engaged in understanding these gaps and driving investigative toxicology towards addressing them. © The Author(s) 2015.

  7. Improvements and limitations on understanding of atmospheric processes of Fukushima Daiichi NPS radioactivity

    NASA Astrophysics Data System (ADS)

    Yamazawa, Hiromi; Terasaka, Yuta; Mizutani, Kenta; Sugiura, Hiroki; Hirao, Shigekazu

    2017-04-01

    Understanding on the release of radioactivity into the atmosphere from the accidental units of Fukushima Daiichi Nuclear Power Station have been improved owing to recent analyses of atmospheric concentrations of radionuclide. Our analysis of gamma-ray spectra from monitoring posts located about 100 km to the south of the site revealed temporal changes of atmospheric concentrations of several key nuclides including noble gas Xe-133 in addition to radio-iodine and cesium nuclides, including I-131 and Cs-137, at a 10 minute interval. By using the atmospheric concentration data, in combination with an inverse atmospheric transport modelling with a Bayesian statistical method, a modification was proposed for the widely used Katata's source term. A source term for Xe-133 was also proposed. Although the atmospheric concentration data and the source terms help us understand the atmospheric transport processes of radionuclides, they still have significant uncertainty due to limitations in availability of the concentration data. There still remain limitations in the atmospheric transport modeling. The largest uncertainty in the model is in the deposition processes. It had been pointed out that, in the 100 km range from the accidental site, there were locations at which the ambient dose rate significantly increased a few hours before precipitation detectors recorded the start of rain. According to our analysis, the dose rate increase was not directly caused by the air-borne radioactivity but by deposition. This phenomenon can be attributed to a deposition process in which evaporating precipitation enhances efficiency of deposition even in a case where no precipitation is observed at ground level.

  8. Political and Institutional Influences on the Use of Evidence in Public Health Policy. A Systematic Review

    PubMed Central

    Liverani, Marco; Hawkins, Benjamin; Parkhurst, Justin O.

    2013-01-01

    Background There is increasing recognition that the development of evidence-informed health policy is not only a technical problem of knowledge exchange or translation, but also a political challenge. Yet, while political scientists have long considered the nature of political systems, the role of institutional structures, and the political contestation of policy issues as central to understanding policy decisions, these issues remain largely unexplored by scholars of evidence-informed policy making. Methods We conducted a systematic review of empirical studies that examined the influence of key features of political systems and institutional mechanisms on evidence use, and contextual factors that may contribute to the politicisation of health evidence. Eligible studies were identified through searches of seven health and social sciences databases, websites of relevant organisations, the British Library database, and manual searches of academic journals. Relevant findings were extracted using a uniform data extraction tool and synthesised by narrative review. Findings 56 studies were selected for inclusion. Relevant political and institutional aspects affecting the use of health evidence included the level of state centralisation and democratisation, the influence of external donors and organisations, the organisation and function of bureaucracies, and the framing of evidence in relation to social norms and values. However, our understanding of such influences remains piecemeal given the limited number of empirical analyses on this subject, the paucity of comparative works, and the limited consideration of political and institutional theory in these studies. Conclusions This review highlights the need for a more explicit engagement with the political and institutional factors affecting the use of health evidence in decision-making. A more nuanced understanding of evidence use in health policy making requires both additional empirical studies of evidence use, and an engagement with theories and approaches beyond the current remit of public health or knowledge utilisation studies. PMID:24204823

  9. Problematising risk in stroke rehabilitation.

    PubMed

    Egan, Mary Y; Kessler, Dorothy; Ceci, Christine; Laliberté-Rudman, Debbie; McGrath, Colleen; Sikora, Lindsey; Gardner, Paula

    2016-11-01

    Following stroke, re-engagement in personally valued activities requires some experience of risk. Risk, therefore, must be seen as having positive as well as negative aspects in rehabilitation. Our aim was to identify the dominant understanding of risk in stroke rehabilitation and the assumptions underpinning these understandings, determine how these understandings affect research and practise, and if necessary, propose alternate ways to conceptualise risk in research and practise. Alvesson and Sandberg's method of problematisation was used. We began with a historical overview of stroke rehabilitation, and proceeded through five steps undertaken in an iterative fashion: literature search and selection; data extraction; syntheses across texts; identification of assumptions informing the literature and; generation of alternatives. Discussion of risk in stroke rehabilitation is largely implicit. However, two prominent conceptualisations of risk underpin both knowledge development and clinical practise: the risk to the individual stroke survivor of remaining dependent in activities of daily living and the risk that the health care system will be overwhelmed by the costs of providing stroke rehabilitation. Conceptualisation of risk in stroke rehabilitation, while implicit, drives both research and practise in ways that reinforce a focus on impairment and a generic, decontextualised approach to rehabilitation. Implications for rehabilitation Much of stroke rehabilitation practise and research seems to centre implicitly on two risks: risk to the patient of remaining dependent in ADL and risk to the health care system of bankruptcy due to the provision of stroke rehabilitation. The implicit focus on ADL dependence limits the ability of clinicians and researchers to address other goals supportive of a good life following stroke. The implicit focus on financial risk to the health care system may limit access to rehabilitation for people who have experienced either milder or more severe stroke. Viewing individuals affected by stroke as possessing a range of independence and diverse personally valued activities that exist within a network of relations offers wider possibilities for action in rehabilitation.

  10. Organic contaminant transport and fate in the subsurface: Evolution of knowledge and understanding

    NASA Astrophysics Data System (ADS)

    Essaid, Hedeff I.; Bekins, Barbara A.; Cozzarelli, Isabelle M.

    2015-07-01

    Toxic organic contaminants may enter the subsurface as slightly soluble and volatile nonaqueous phase liquids (NAPLs) or as dissolved solutes resulting in contaminant plumes emanating from the source zone. A large body of research published in Water Resources Research has been devoted to characterizing and understanding processes controlling the transport and fate of these organic contaminants and the effectiveness of natural attenuation, bioremediation, and other remedial technologies. These contributions include studies of NAPL flow, entrapment, and interphase mass transfer that have advanced from the analysis of simple systems with uniform properties and equilibrium contaminant phase partitioning to complex systems with pore-scale and macroscale heterogeneity and rate-limited interphase mass transfer. Understanding of the fate of dissolved organic plumes has advanced from when biodegradation was thought to require oxygen to recognition of the importance of anaerobic biodegradation, multiple redox zones, microbial enzyme kinetics, and mixing of organic contaminants and electron acceptors at plume fringes. Challenges remain in understanding the impacts of physical, chemical, biological, and hydrogeological heterogeneity, pore-scale interactions, and mixing on the fate of organic contaminants. Further effort is needed to successfully incorporate these processes into field-scale predictions of transport and fate. Regulations have greatly reduced the frequency of new point-source contamination problems; however, remediation at many legacy plumes remains challenging. A number of fields of current relevance are benefiting from research advances from point-source contaminant research. These include geologic carbon sequestration, nonpoint-source contamination, aquifer storage and recovery, the fate of contaminants from oil and gas development, and enhanced bioremediation.

  11. Organic contaminant transport and fate in the subsurface: evolution of knowledge and understanding

    USGS Publications Warehouse

    Essaid, Hedeff I.; Bekins, Barbara A.; Cozzarelli, Isabelle M.

    2015-01-01

    Toxic organic contaminants may enter the subsurface as slightly soluble and volatile nonaqueous phase liquids (NAPLs) or as dissolved solutes resulting in contaminant plumes emanating from the source zone. A large body of research published in Water Resources Research has been devoted to characterizing and understanding processes controlling the transport and fate of these organic contaminants and the effectiveness of natural attenuation, bioremediation, and other remedial technologies. These contributions include studies of NAPL flow, entrapment, and interphase mass transfer that have advanced from the analysis of simple systems with uniform properties and equilibrium contaminant phase partitioning to complex systems with pore-scale and macroscale heterogeneity and rate-limited interphase mass transfer. Understanding of the fate of dissolved organic plumes has advanced from when biodegradation was thought to require oxygen to recognition of the importance of anaerobic biodegradation, multiple redox zones, microbial enzyme kinetics, and mixing of organic contaminants and electron acceptors at plume fringes. Challenges remain in understanding the impacts of physical, chemical, biological, and hydrogeological heterogeneity, pore-scale interactions, and mixing on the fate of organic contaminants. Further effort is needed to successfully incorporate these processes into field-scale predictions of transport and fate. Regulations have greatly reduced the frequency of new point-source contamination problems; however, remediation at many legacy plumes remains challenging. A number of fields of current relevance are benefiting from research advances from point-source contaminant research. These include geologic carbon sequestration, nonpoint-source contamination, aquifer storage and recovery, the fate of contaminants from oil and gas development, and enhanced bioremediation.

  12. Integrating uncertainties for climate change mitigation

    NASA Astrophysics Data System (ADS)

    Rogelj, Joeri; McCollum, David; Reisinger, Andy; Meinshausen, Malte; Riahi, Keywan

    2013-04-01

    The target of keeping global average temperature increase to below 2°C has emerged in the international climate debate more than a decade ago. In response, the scientific community has tried to estimate the costs of reaching such a target through modelling and scenario analysis. Producing such estimates remains a challenge, particularly because of relatively well-known, but ill-quantified uncertainties, and owing to limited integration of scientific knowledge across disciplines. The integrated assessment community, on one side, has extensively assessed the influence of technological and socio-economic uncertainties on low-carbon scenarios and associated costs. The climate modelling community, on the other side, has worked on achieving an increasingly better understanding of the geophysical response of the Earth system to emissions of greenhouse gases (GHG). This geophysical response remains a key uncertainty for the cost of mitigation scenarios but has only been integrated with assessments of other uncertainties in a rudimentary manner, i.e., for equilibrium conditions. To bridge this gap between the two research communities, we generate distributions of the costs associated with limiting transient global temperature increase to below specific temperature limits, taking into account uncertainties in multiple dimensions: geophysical, technological, social and political. In other words, uncertainties resulting from our incomplete knowledge about how the climate system precisely reacts to GHG emissions (geophysical uncertainties), about how society will develop (social uncertainties and choices), which technologies will be available (technological uncertainty and choices), when we choose to start acting globally on climate change (political choices), and how much money we are or are not willing to spend to achieve climate change mitigation. We find that political choices that delay mitigation have the largest effect on the cost-risk distribution, followed by geophysical, future energy demand, and mitigation technology uncertainties. This information provides central information for policy making, since it helps to understand the relationship between mitigation costs and their potential to reduce the risk of exceeding 2°C, or other temperature limits like 3°C or 1.5°C, under a wide range of scenarios.

  13. Mathematical and Computational Modeling in Complex Biological Systems

    PubMed Central

    Li, Wenyang; Zhu, Xiaoliang

    2017-01-01

    The biological process and molecular functions involved in the cancer progression remain difficult to understand for biologists and clinical doctors. Recent developments in high-throughput technologies urge the systems biology to achieve more precise models for complex diseases. Computational and mathematical models are gradually being used to help us understand the omics data produced by high-throughput experimental techniques. The use of computational models in systems biology allows us to explore the pathogenesis of complex diseases, improve our understanding of the latent molecular mechanisms, and promote treatment strategy optimization and new drug discovery. Currently, it is urgent to bridge the gap between the developments of high-throughput technologies and systemic modeling of the biological process in cancer research. In this review, we firstly studied several typical mathematical modeling approaches of biological systems in different scales and deeply analyzed their characteristics, advantages, applications, and limitations. Next, three potential research directions in systems modeling were summarized. To conclude, this review provides an update of important solutions using computational modeling approaches in systems biology. PMID:28386558

  14. Mathematical and Computational Modeling in Complex Biological Systems.

    PubMed

    Ji, Zhiwei; Yan, Ke; Li, Wenyang; Hu, Haigen; Zhu, Xiaoliang

    2017-01-01

    The biological process and molecular functions involved in the cancer progression remain difficult to understand for biologists and clinical doctors. Recent developments in high-throughput technologies urge the systems biology to achieve more precise models for complex diseases. Computational and mathematical models are gradually being used to help us understand the omics data produced by high-throughput experimental techniques. The use of computational models in systems biology allows us to explore the pathogenesis of complex diseases, improve our understanding of the latent molecular mechanisms, and promote treatment strategy optimization and new drug discovery. Currently, it is urgent to bridge the gap between the developments of high-throughput technologies and systemic modeling of the biological process in cancer research. In this review, we firstly studied several typical mathematical modeling approaches of biological systems in different scales and deeply analyzed their characteristics, advantages, applications, and limitations. Next, three potential research directions in systems modeling were summarized. To conclude, this review provides an update of important solutions using computational modeling approaches in systems biology.

  15. Cell biology of the Koji mold Aspergillus oryzae.

    PubMed

    Kitamoto, Katsuhiko

    2015-01-01

    Koji mold, Aspergillus oryzae, has been used for the production of sake, miso, and soy sauce for more than one thousand years in Japan. Due to the importance, A. oryzae has been designated as the national micro-organism of Japan (Koku-kin). A. oryzae has been intensively studied in the past century, with most investigations focusing on breeding techniques and developing methods for Koji making for sake brewing. However, the understanding of fundamental biology of A. oryzae remains relatively limited compared with the yeast Saccharomyces cerevisiae. Therefore, we have focused on studying the cell biology including live cell imaging of organelles, protein vesicular trafficking, autophagy, and Woronin body functions using the available genomic information. In this review, I describe essential findings of cell biology of A. oryzae obtained in our study for a quarter of century. Understanding of the basic biology will be critical for not its biotechnological application, but also for an understanding of the fundamental biology of other filamentous fungi.

  16. Commercial sexual exploitation and sex trafficking of adolescents.

    PubMed

    Chung, Richard J; English, Abigail

    2015-08-01

    This review describes the current state of commercial sexual exploitation and sex trafficking of adolescents in the United States and globally, the legal and health implications of this severe form of abuse, and the roles that pediatric and adolescent healthcare providers can play in addressing this issue. Although this form of exploitation and abuse is shrouded in secrecy, pediatric and adolescent healthcare providers are well positioned to respond when it arises. However, awareness and understanding of the issue are generally lacking among healthcare professionals, currently limiting their effectiveness in combating this problem. Although the empirical evidence base available to guide clinical care of victims of trafficking remains limited given the secretive nature of the abuse, important contributions to the multidisciplinary literature on this issue have been made in recent years, including the Institute of Medicine's landmark report in the United States. Commercial sexual exploitation and sex trafficking of adolescents represent a human rights tragedy that remains inadequately addressed. As preeminent advocates for the health and well-being of adolescents, pediatric and adolescent healthcare providers can play a crucial role in advancing efforts not only to intervene but also to prevent further victimization of vulnerable youth.

  17. Measuring meaning and peace with the FACIT-spiritual well-being scale: distinction without a difference?

    PubMed

    Peterman, Amy H; Reeve, Charlie L; Winford, Eboni C; Cotton, Sian; Salsman, John M; McQuellon, Richard; Tsevat, Joel; Campbell, Cassie

    2014-03-01

    The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp; Peterman, Fitchett, Brady, Hernandez, & Cella, 2002) has become a widely used measure of spirituality; however, there remain questions about its specific factor structure and the validity of scores from its separate scales. Specifically, it remains unclear whether the Meaning and Peace scales denote distinct factors. The present study addresses previous limitations by examining the extent to which the Meaning and Peace scales relate differentially to a variety of physical and mental health variables across 4 sets of data from adults with a number of chronic health conditions. Although a model with separate but correlated factors fit the data better, discriminant validity analyses indicated limited differences in the pattern of associations each scale showed with a wide array of commonly used health and quality-of-life measures. In total, the results suggest that people may distinguish between the concepts of Meaning and Peace, but the observed relations with health outcomes are primarily due to variance shared between the 2 factors. Additional research is needed to better understand the separate and joint role of Meaning and Peace in the quality of life of people with chronic illness. 2014 APA

  18. Measuring Meaning and Peace With the FACIT–Spiritual Well-Being Scale: Distinction Without a Difference?

    PubMed Central

    Peterman, Amy H.; Reeve, Charlie L.; Winford, Eboni C.; Salsman, John M.; Tsevat, Joel; Cotton, Sian; McQuellon, Richard; Campbell, Cassie

    2014-01-01

    The Functional Assessment of Chronic Illness Therapy–Spiritual Well-Being Scale (FACIT–Sp; Peterman, Fitchett, Brady, Hernandez, & Cella, 2002) has become a widely used measure of spirituality; however, there remain questions about its specific factor structure and the validity of scores from its separate scales. Specifically, it remains unclear whether the Meaning and Peace scales denote distinct factors. The present study addresses previous limitations by examining the extent to which the Meaning and Peace scales relate differentially to a variety of physical and mental health variables across 4 sets of data from adults with a number of chronic health conditions. Although a model with separate but correlated factors fit the data better, discriminant validity analyses indicated limited differences in the pattern of associations each scale showed with a wide array of commonly used health and quality-of-life measures. In total, the results suggest that people may distinguish between the concepts of Meaning and Peace, but the observed relations with health outcomes are primarily due to variance shared between the 2 factors. Additional research is needed to better understand the separate and joint role of Meaning and Peace in the quality of life of people with chronic illness. PMID:24188147

  19. Metabolic costs imposed by hydrostatic pressure constrain bathymetric range in the lithodid crab Lithodes maja.

    PubMed

    Brown, Alastair; Thatje, Sven; Morris, James P; Oliphant, Andrew; Morgan, Elizabeth A; Hauton, Chris; Jones, Daniel O B; Pond, David W

    2017-11-01

    The changing climate is shifting the distributions of marine species, yet the potential for shifts in depth distributions is virtually unexplored. Hydrostatic pressure is proposed to contribute to a physiological bottleneck constraining depth range extension in shallow-water taxa. However, bathymetric limitation by hydrostatic pressure remains undemonstrated, and the mechanism limiting hyperbaric tolerance remains hypothetical. Here, we assess the effects of hydrostatic pressure in the lithodid crab Lithodes maja (bathymetric range 4-790 m depth, approximately equivalent to 0.1 to 7.9 MPa hydrostatic pressure). Heart rate decreased with increasing hydrostatic pressure, and was significantly lower at ≥10.0 MPa than at 0.1 MPa. Oxygen consumption increased with increasing hydrostatic pressure to 12.5 MPa, before decreasing as hydrostatic pressure increased to 20.0 MPa; oxygen consumption was significantly higher at 7.5-17.5 MPa than at 0.1 MPa. Increases in expression of genes associated with neurotransmission, metabolism and stress were observed between 7.5 and 12.5 MPa. We suggest that hyperbaric tolerance in L maja may be oxygen-limited by hyperbaric effects on heart rate and metabolic rate, but that L maja 's bathymetric range is limited by metabolic costs imposed by the effects of high hydrostatic pressure. These results advocate including hydrostatic pressure in a complex model of environmental tolerance, where energy limitation constrains biogeographic range, and facilitate the incorporation of hydrostatic pressure into the broader metabolic framework for ecology and evolution. Such an approach is crucial for accurately projecting biogeographic responses to changing climate, and for understanding the ecology and evolution of life at depth. © 2017. Published by The Company of Biologists Ltd.

  20. Discovering Network Structure Beyond Communities

    NASA Astrophysics Data System (ADS)

    Nishikawa, Takashi; Motter, Adilson E.

    2011-11-01

    To understand the formation, evolution, and function of complex systems, it is crucial to understand the internal organization of their interaction networks. Partly due to the impossibility of visualizing large complex networks, resolving network structure remains a challenging problem. Here we overcome this difficulty by combining the visual pattern recognition ability of humans with the high processing speed of computers to develop an exploratory method for discovering groups of nodes characterized by common network properties, including but not limited to communities of densely connected nodes. Without any prior information about the nature of the groups, the method simultaneously identifies the number of groups, the group assignment, and the properties that define these groups. The results of applying our method to real networks suggest the possibility that most group structures lurk undiscovered in the fast-growing inventory of social, biological, and technological networks of scientific interest.

  1. Advances in the understanding, management, and prevention of dengue.

    PubMed

    Hermann, Laura L; Gupta, Swati B; Manoff, Susan B; Kalayanarooj, Siripen; Gibbons, Robert V; Coller, Beth-Ann G

    2015-03-01

    Dengue causes more human morbidity globally than any other vector-borne viral disease. Recent research has led to improved epidemiological methods that predict disease burden and factors involved in transmission, a better understanding of immune responses in infection, and enhanced animal models. In addition, a number of control measures, including preventative vaccines, are in clinical trials. However, significant gaps remain, including the need for better surveillance in large parts of the world, methods to predict which individuals will develop severe disease, and immunologic correlates of protection against dengue illness. During the next decade, dengue will likely expand its geographic reach and become an increasing burden on health resources in affected areas. Licensed vaccines and antiviral agents are needed in order to effectively control dengue and limit disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. High Performance Nano-Crystalline Oxide Fuel Cell Materials. Defects, Structures, Interfaces, Transport, and Electrochemistry

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

    Barnett, Scott; Poeppelmeier, Ken; Mason, Tom

    This project addresses fundamental materials challenges in solid oxide electrochemical cells, devices that have a broad range of important energy applications. Although nano-scale mixed ionically and electronically conducting (MIEC) materials provide an important opportunity to improve performance and reduce device operating temperature, durability issues threaten to limit their utility and have remained largely unexplored. Our work has focused on both (1) understanding the fundamental processes related to oxygen transport and surface-vapor reactions in nano-scale MIEC materials, and (2) determining and understanding the key factors that control their long-term stability. Furthermore, materials stability has been explored under the “extreme” conditions encounteredmore » in many solid oxide cell applications, i.e, very high or very low effective oxygen pressures, and high current density.« less

  3. CA 15-3 predicting breast cancer relapse: beware of vitamin B12 deficiency.

    PubMed

    Rassy, Elie El; Ghor, Maya Al; Kattan, Joseph

    2018-05-10

    A sustained increase of cancer antigen 15-3 serum levels was found in a 54-year-old woman treated 2 years ago for early stage breast cancer, without any evidence of cancer recurrence. The patient thereafter developed severe megaloblastic anemia secondary to vitamin B12 deficiency. Supplementation with B12 to reverse the anemia led to the normalization of the cancer antigen 15-3 serum levels. As such, with the limited understanding of molecular biology, the integrative approach of clinical history, physical examination, and diagnostic imaging remain pivotal in the management of cancer patients.

  4. Equilibrium Sampling in Biomolecular Simulation

    PubMed Central

    2015-01-01

    Equilibrium sampling of biomolecules remains an unmet challenge after more than 30 years of atomistic simulation. Efforts to enhance sampling capability, which are reviewed here, range from the development of new algorithms to parallelization to novel uses of hardware. Special focus is placed on classifying algorithms — most of which are underpinned by a few key ideas — in order to understand their fundamental strengths and limitations. Although algorithms have proliferated, progress resulting from novel hardware use appears to be more clear-cut than from algorithms alone, partly due to the lack of widely used sampling measures. PMID:21370970

  5. Occupational Therapy for Adults With Cancer: Why It Matters.

    PubMed

    Pergolotti, Mackenzi; Williams, Grant R; Campbell, Claudine; Munoz, Lauro A; Muss, Hyman B

    2016-03-01

    Adults with cancer may be at risk for limitations in functional status and quality of life (QOL). Occupational therapy is a supportive service with the specific mission to help people functionally engage in life as safely and independently as possible with the primary goal of improving QOL. Unfortunately, for people with cancer, occupational therapy remains underused. The overall purpose of this review is to provide an understanding of what occupational therapy is and its relevance to patients with cancer, highlight the reasons to refer, and, last, provide general advice on how to access services. ©AlphaMed Press.

  6. Persistence of soil organic matter as an ecosystem property.

    PubMed

    Schmidt, Michael W I; Torn, Margaret S; Abiven, Samuel; Dittmar, Thorsten; Guggenberger, Georg; Janssens, Ivan A; Kleber, Markus; Kögel-Knabner, Ingrid; Lehmann, Johannes; Manning, David A C; Nannipieri, Paolo; Rasse, Daniel P; Weiner, Steve; Trumbore, Susan E

    2011-10-05

    Globally, soil organic matter (SOM) contains more than three times as much carbon as either the atmosphere or terrestrial vegetation. Yet it remains largely unknown why some SOM persists for millennia whereas other SOM decomposes readily--and this limits our ability to predict how soils will respond to climate change. Recent analytical and experimental advances have demonstrated that molecular structure alone does not control SOM stability: in fact, environmental and biological controls predominate. Here we propose ways to include this understanding in a new generation of experiments and soil carbon models, thereby improving predictions of the SOM response to global warming.

  7. Potential Targets for Antifungal Drug Discovery Based on Growth and Virulence in Candida albicans

    PubMed Central

    Li, Xiuyun; Hou, Yinglong; Yue, Longtao; Liu, Shuyuan; Du, Juan

    2015-01-01

    Fungal infections, especially infections caused by Candida albicans, remain a challenging problem in clinical settings. Despite the development of more-effective antifungal drugs, their application is limited for various reasons. Thus, alternative treatments with drugs aimed at novel targets in C. albicans are needed. Knowledge of growth and virulence in fungal cells is essential not only to understand their pathogenic mechanisms but also to identify potential antifungal targets. This article reviews the current knowledge of the mechanisms of growth and virulence in C. albicans and examines potential targets for the development of new antifungal drugs. PMID:26195510

  8. Persistence of soil organic matter as an ecosystem property

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

    Schmidt, M.W.; Torn, M. S.; Abiven, S.

    2011-08-15

    Globally, soil organic matter (SOM) contains more than three times as much carbon as either the atmosphere or terrestrial vegetation. Yet it remains largely unknown why some SOM persists for millennia whereas other SOM decomposes readily—and this limits our ability to predict how soils will respond to climate change. Recent analytical and experimental advances have demonstrated that molecular structure alone does not control SOM stability: in fact, environmental and biological controls predominate. Here we propose ways to include this understanding in a new generation of experiments and soil carbon models, thereby improving predictions of the SOM response to global warming.

  9. Complex function in the dynamic brain. Comment on “Understanding brain networks and brain organization” by Luiz Pessoa

    NASA Astrophysics Data System (ADS)

    Anderson, Michael L.

    2014-09-01

    There is much to commend in this excellent overview of the progress we've made toward-and the challenges that remain for-developing an empirical framework for neuroscience that is adequate to the dynamic complexity of the brain [17]. Here I will limit myself first to highlighting the concept of dynamic affiliation, which I take to be the central feature of the functional architecture of the brain, and second to clarifying Pessoa's brief discussion of the ontology of cognition, to be sure readers appreciate this crucial issue.

  10. Jovian decametric radiation seen from Juno, Cassini, STEREO A, WIND, and Earth-based radio observatories

    NASA Astrophysics Data System (ADS)

    Imai, M.; Kurth, W. S.; Hospodarsky, G. B.; Bolton, S. J.; Connerney, J. E. P.; Levin, S. M.; Lecacheux, A.; Lamy, L.; Zarka, P.; Clarke, T. E.; Higgins, C. A.

    2017-09-01

    Jupiter's decametric (DAM) radiation is generated very close to the local gyrofrequency by the electron cyclotron maser instability (CMI). The first two-point common detections of Jovian DAM radiation were made using the Voyager spacecraft and ground-based radio observatories in early 1979, but, due to geometrical constraints and limited flyby duration, a full understanding of the latitudinal beaming of Jovian DAM radiation remains elusive. The stereoscopic DAM radiation viewed from Juno, Cassini, STEREO A, WIND, and Earth-based radio observatories provides a unique opportunity to analyze the CMI emission mechanism and beaming properties.

  11. Proceedings of the Airframe Icing Workshop

    NASA Technical Reports Server (NTRS)

    Colantonio, Ron O. (Editor)

    2009-01-01

    The NASA Glenn Research Center (GRC) has a long history of working with its partners towards the understanding of ice accretion formation and its associated degradation of aerodynamic performance. The June 9, 2009, Airframe Icing Workshop held at GRC provided an opportunity to examine the current NASA airframe icing research program and to dialogue on remaining and emerging airframe icing issues and research with the external community. Some of the airframe icing gaps identified included, but are not limited to, ice accretion simulation enhancements, three-dimensional benchmark icing database development, three-dimensional iced aerodynamics modeling, and technology development for a smart icing system.

  12. From novelty to the every-day: the evolution of ureteroscopy.

    PubMed

    Ridyard, Douglas; Dagrosa, Lawrence; Pais, Vernon M

    2016-12-01

    Ureteroscopy revolutionized the surgical approach to the upper urinary tract, and is well recognized as a cornerstone of modern urology. Although now commonplace, ureteroscopic equipment and techniques were truly revolutionary. A review of the innovations and innovators that developed ureteroscopic surgery sets the stage for a more thorough understanding of what can be done ureteroscopically, and may additionally better inform what limitations remain. Given that future advancements in urologic therapy will be dependent upon a similar pursuit of paradigm shifting improvements in disease management, an overview of the development of modern ureteroscopy may inspire such change.

  13. MicroRNAs are important regulators of drug resistance in colorectal cancer

    PubMed Central

    Zhang, Yang; Wang, Jing

    2018-01-01

    Despite of continuous development of cancer treatment over the past decades, drug resistance is still one of the major hurdles of effective therapy for advanced colorectal cancer (CRC) worldwide and the understanding of its underlying mechanisms remains limited. Emerged data suggests that many microRNAs (miRNAs) may contribute to drug resistance in CRC. Major findings on miRNA functions in drug resistance of CRC are systemically reviewed here, with the goal of providing new updates to broaden our comprehension of its mechanisms and evidence to utilize miRNAs as potential therapeutic targets for CRC treatment. PMID:28095367

  14. Fifty Years of Research in ARDS. Is Acute Respiratory Distress Syndrome a Preventable Disease?

    PubMed

    Yadav, Hemang; Thompson, B Taylor; Gajic, Ognjen

    2017-03-15

    Despite significant advances in our understanding and management of patients with acute respiratory distress syndrome (ARDS), the morbidity and mortality from ARDS remains high. Given the limited number of effective treatments for established ARDS, the strategic focus of ARDS research has shifted toward identifying patients with or at high risk of ARDS early in the course of the underlying illness, when strategies to reduce the development and progression of ARDS and associated organ failures can be systematically evaluated. In this review, we summarize the rationale, current evidence, and future directions in ARDS prevention.

  15. A Novel Experimental and Analytical Approach to the Multimodal Neural Decoding of Intent During Social Interaction in Freely-behaving Human Infants.

    PubMed

    Cruz-Garza, Jesus G; Hernandez, Zachery R; Tse, Teresa; Caducoy, Eunice; Abibullaev, Berdakh; Contreras-Vidal, Jose L

    2015-10-04

    Understanding typical and atypical development remains one of the fundamental questions in developmental human neuroscience. Traditionally, experimental paradigms and analysis tools have been limited to constrained laboratory tasks and contexts due to technical limitations imposed by the available set of measuring and analysis techniques and the age of the subjects. These limitations severely limit the study of developmental neural dynamics and associated neural networks engaged in cognition, perception and action in infants performing "in action and in context". This protocol presents a novel approach to study infants and young children as they freely organize their own behavior, and its consequences in a complex, partly unpredictable and highly dynamic environment. The proposed methodology integrates synchronized high-density active scalp electroencephalography (EEG), inertial measurement units (IMUs), video recording and behavioral analysis to capture brain activity and movement non-invasively in freely-behaving infants. This setup allows for the study of neural network dynamics in the developing brain, in action and context, as these networks are recruited during goal-oriented, exploration and social interaction tasks.

  16. Sleep in amphibians and reptiles: a review and a preliminary analysis of evolutionary patterns.

    PubMed

    Libourel, Paul-Antoine; Herrel, Anthony

    2016-08-01

    Despite the ubiquitous nature of sleep, its functions remain a mystery. In an attempt to address this, many researchers have studied behavioural and electrophysiological phenomena associated with sleep in a diversity of animals. The great majority of vertebrates and invertebrates display a phase of immobility that could be considered as a sort of sleep. Terrestrial mammals and birds, both homeotherms, show two sleep states with distinct behavioural and electrophysiological features. However, whether these features have evolved independently in each clade or were inherited from a common ancestor remains unknown. Unfortunately, amphibians and reptiles, key taxa in understanding the evolution of sleep given their position at the base of the tetrapod and amniote tree, respectively, remain poorly studied in the context of sleep. This review presents an overview of what is known about sleep in amphibians and reptiles and uses the existing data to provide a preliminary analysis of the evolution of behavioural and electrophysiological features of sleep in amphibians and reptiles. We also discuss the problems associated with analysing existing data, as well as the difficulty in inferring homologies of sleep stages based on limited data in the context of an essentially mammalian-centric definition of sleep. Finally, we highlight the importance of developing comparative approaches to sleep research that may benefit from the great diversity of species with different ecologies and morphologies in order to understand the evolution and functions of sleep. © 2015 Cambridge Philosophical Society.

  17. Drought and tree mortality in tropical rainforest: understanding and differentiating functional responses

    NASA Astrophysics Data System (ADS)

    Meir, P.; Rowland, L.; da Costa, A. C. L.; Mencuccini, M.; Oliveira, A.; Binks, O.; Christoffersen, B. O.; Eliane, M.; Vasconcelos, S.; Kruijt, B.; Ferreira, L.

    2014-12-01

    Our understanding of how forests respond to drought is especially constrained with respect to widespread tree mortality events. This limitation is particularly clear for tropical forests, despite the risk of drought to these ecosystems during the coming decades. We present new findings from the only current long-term 'ecosystem-scale' (1 ha) rainfall manipulation experiment in tropical rainforest, the Esecaflor experiment at Caxiuana National Forest, Para State, Brazil. Throughfall has been partially excluded from experimental forest at the Esecaflor experiment for more than a decade. We have previously demonstrated a capacity to model short-term physiological responses well, but longer term physiology and ecological dynamics remain challenging to understand and represent. In particular, high mortality and increased autotrophic respiration following extended drought are poorly understood phenomena, and their interaction with hydraulic responses and limitations needs to be characterised. We present initial data that for the first time combine carbon use and hydraulic metrics, comparing drought-vulnerable and non-vulnerable species that have experienced extended soil moisture deficit, as imposed in the experiment, also considering the response in soil respiration. We also discuss how these findings can be used to develop future empirical and modelling studies aimed at improving our capacity to predict the effects of drought on tropical forest ecosystems in Amazonia and in other tropical forest regions where species characteristics and environmental constraints may influence both short and long-term responses to drought.

  18. Relapsing Painful Ophthalmoplegic Neuropathy: No longer a "Migraine," but Still a Headache.

    PubMed

    Smith, Stacy V; Schuster, Nathaniel M

    2018-06-14

    Recurrent painful ophthalmoplegic neuropathy (RPON), formerly known as ophthalmoplegic migraine, is an uncommon disorder with repeated episodes of ocular cranial nerve neuropathy associated with ipsilateral headache. This review discusses the clinical presentation, current understanding of the pathophysiology, key differential diagnoses, and evaluation and treatment of RPON. The literature is limited due to the rarity of the disorder. Recent case reports and series continue to suggest the age of first attack is most often during childhood or adolescence as well as a female predominance. Multiple recent case reports and series demonstrate focal enhancement of the affected cranial nerve, as the nerve root exits the brainstem. This finding contributed to the current classification of the disorder as a neuropathy, with the present understanding that it is due to a relapsing-remitting inflammatory or demyelinating process. The link to migraine remains a cause of disagreement in the literature. RPON is a complex disorder with features of inflammatory neuropathy and an unclear association with migraine. Regardless, the overall prognosis is good for individual episodes, but permanent nerve damage may accumulate with repeated attacks. A better understanding of the pathogenesis is needed to clarify whether it truly represents a single disorder and to guide its treatment. Until that time, a combined approach with acute and preventive therapies can mitigate acute symptoms as well as attempt to limit recurrence of this disabling syndrome.

  19. Enzymology under global change: organic nitrogen turnover in alpine and sub-Arctic soils.

    PubMed

    Weedon, James T; Aerts, Rien; Kowalchuk, George A; van Bodegom, Peter M

    2011-01-01

    Understanding global change impacts on the globally important carbon storage in alpine, Arctic and sub-Arctic soils requires knowledge of the mechanisms underlying the balance between plant primary productivity and decomposition. Given that nitrogen availability limits both processes, understanding the response of the soil nitrogen cycle to shifts in temperature and other global change factors is crucial for predicting the fate of cold biome carbon stores. Measurements of soil enzyme activities at different positions of the nitrogen cycling network are an important tool for this purpose. We review a selection of studies that provide data on potential enzyme activities across natural, seasonal and experimental gradients in cold biomes. Responses of enzyme activities to increased nitrogen availability and temperature are diverse and seasonal dynamics are often larger than differences due to experimental treatments, suggesting that enzyme expression is regulated by a combination of interacting factors reflecting both nutrient supply and demand. The extrapolation from potential enzyme activities to prediction of elemental nitrogen fluxes under field conditions remains challenging. Progress in molecular '-omics' approaches may eventually facilitate deeper understanding of the links between soil microbial community structure and biogeochemical fluxes. In the meantime, accounting for effects of the soil spatial structure and in situ variations in pH and temperature, better mapping of the network of enzymatic processes and the identification of rate-limiting steps under different conditions should advance our ability to predict nitrogen fluxes.

  20. Flower power: Floral and resource manipulations reveal how and why reproductive trade-offs occur for lowbush blueberry (Vaccinium angustifolium).

    PubMed

    Bajcz, Alex W; Drummond, Francis A

    2017-08-01

    Plant reproductive trade-offs are thought to be caused by resource limitations or other constraints, but more empirical support for these hypotheses would be welcome. Additionally, quantitative characterization of these trade-offs, as well as consideration of whether they are linear, could yield additional insights. We expanded our flower removal research on lowbush blueberry ( Vaccinium angustifolium ) to explore the nature of and causes of its reproductive trade-offs. We used fertilization, defoliation, positionally biased flower removal, and multiple flower removal levels to discern why reproductive trade-offs occur in this taxon and to plot these trade-offs along two continuous axes. We found evidence through defoliation that vegetative mass per stem may trade off with reproductive effort in lowbush blueberry because the two traits compete for limited carbon. Also, several traits including ripe fruit production per reproductive node and fruit titratable acidity may be "sink-limited"-they decline with increasing reproductive effort because average reproductive structure quality declines. We found no evidence that reproductive trade-offs were caused by nitrogen limitation. Use of reproductive nodes remaining per stem as a measure of reproductive effort indicated steeper trade-offs than use of the proportion of nodes remaining. For five of six traits, we found evidence that the trade-off could be concave down or up instead of strictly linear. Synthesis . To date, studies have aimed primarily at identifying plant reproductive trade-offs. However, understanding how and why these trade-offs occur represent the exciting and necessary next steps for this line of inquiry.

  1. Mapping Neurodegenerative Disease Onset and Progression.

    PubMed

    Seeley, William W

    2017-08-01

    Brain networks have been of long-standing interest to neurodegeneration researchers, including but not limited to investigators focusing on conventional prion diseases, which are known to propagate along neural pathways. Tools for human network mapping, however, remained inadequate, limiting our understanding of human brain network architecture and preventing clinical research applications. Until recently, neuropathological studies were the only viable approach to mapping disease onset and progression in humans but required large autopsy cohorts and laborious methods for whole-brain sectioning and staining. Despite important advantages, postmortem studies cannot address in vivo, physiological, or longitudinal questions and have limited potential to explore early-stage disease except for the most common disorders. Emerging in vivo network-based neuroimaging strategies have begun to address these issues, providing data that complement the neuropathological tradition. Overall, findings to date highlight several fundamental principles of neurodegenerative disease anatomy and pathogenesis, as well as some enduring mysteries. These principles and mysteries provide a road map for future research. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  2. Use of Lower-Limb Robotics to Enhance Practice and Participation in Individuals With Neurological Conditions.

    PubMed

    Jayaraman, Arun; Burt, Sheila; Rymer, William Zev

    2017-07-01

    To review lower-limb technology currently available for people with neurological disorders, such as spinal cord injury, stroke, or other conditions. We focus on 3 emerging technologies: treadmill-based training devices, exoskeletons, and other wearable robots. Efficacy for these devices remains unclear, although preliminary data indicate that specific patient populations may benefit from robotic training used with more traditional physical therapy. Potential benefits include improved lower-limb function and a more typical gait trajectory. Use of these devices is limited by insufficient data, cost, and in some cases size of the machine. However, robotic technology is likely to become more prevalent as these machines are enhanced and able to produce targeted physical rehabilitation. Therapists should be aware of these technologies as they continue to advance but understand the limitations and challenges posed with therapeutic/mobility robots.

  3. Natural and engineered biosynthesis of fluorinated natural products.

    PubMed

    Walker, Mark C; Chang, Michelle C Y

    2014-09-21

    Both natural products and synthetic organofluorines play important roles in the discovery and design of pharmaceuticals. The combination of these two classes of molecules has the potential to be useful in the ongoing search for new bioactive compounds but our ability to produce site-selectively fluorinated natural products remains limited by challenges in compatibility between their high structural complexity and current methods for fluorination. Living systems provide an alternative route to chemical fluorination and could enable the production of organofluorine natural products through synthetic biology approaches. While the identification of biogenic organofluorines has been limited, the study of the native organisms and enzymes that utilize these compounds can help to guide efforts to engineer the incorporation of this unusual element into complex pharmacologically active natural products. This review covers recent advances in understanding both natural and engineered production of organofluorine natural products.

  4. Assessment of the mechanical properties of the muscle-tendon unit by supersonic shear wave imaging elastography: a review

    PubMed Central

    2018-01-01

    This review aimed to describe the state of the art in muscle-tendon unit (MTU) assessment by supersonic shear wave imaging (SSI) elastography in states of muscle contraction and stretching, during aging, and in response to injury and therapeutic interventions. A consensus exists that MTU elasticity increases during passive stretching or contraction, and decreases after static stretching, electrostimulation, massage, and dry needling. There is currently no agreement regarding changes in the MTU due to aging and injury. Currently, the application of SSI for the purpose of diagnosis, rehabilitation, and physical training remains limited by a number of issues, including the lack of normative value ranges, the lack of consensus regarding the appropriate terminology, and an inadequate understanding of the main technical limitations of this novel technology. PMID:28607322

  5. Energy relaxation mechanisms in capacitively shunted flux qubits

    NASA Astrophysics Data System (ADS)

    Corcoles, Antonio; Rozen, Jim; Rothwell, Mary Beth; Keefe, George; di Vincenzo, David; Ketchen, Mark; Chow, Jerry; Rigetti, Chad; Rohrs, Jack; Borstelmann, Mark; Steffen, Matthias; IBM Quantum Computing Group Team

    2011-03-01

    Energy losses in superconducting qubits remain a major object of study in the road towards scalable, highly coherent qubit devices. The current understanding of the loss mechanisms in these devices is far from being complete and it is sometimes difficult to experimentally separate the different contributions to decoherence. Here we compare a traditional three Josephson-junction flux qubit to the recently implemented capacitively shunted flux qubit, whose energy decay is thought to be limited by dielectric losses arising from native oxides in the shunting capacitor. Keeping all parameters identical except for the shunting capacitance, we obtain energy relaxation times that are comparable for both types of qubit. This suggests that the energy relaxation time is not limited by junction losses in capacitively shunted flux qubits. We discuss some other possible loss mechanisms present in these devices.

  6. Money Now, Money Later: Linking Time Discounting and Criminal Convictions in the Cambridge Study in Delinquent Development.

    PubMed

    Piquero, Alex R; Farrington, David P; Jennings, Wesley G

    2018-04-01

    Two prominent criminological theories offer time discounting, or the preference for an immediate reward over a later one, as a central part of understanding involvement in criminal activity. Yet, there exist only a few studies investigating this issue, and they are limited in a few respects. The current study extends prior work in this area by using multiple measures of time discounting collected at three different periods of the life course to examine the link to criminal offending into late middle adulthood in the Cambridge Study in Delinquent Development. Results show that greater time discounting is positively related to a higher number of criminal convictions by late middle adulthood, and this effect remains after controlling for early life-course individual and environmental risk in a multivariate framework. Study limitations and implications are also discussed.

  7. Chronic Lung Allograft Dysfunction: A Systematic Review of Mechanisms.

    PubMed

    Royer, Pierre-Joseph; Olivera-Botello, Gustavo; Koutsokera, Angela; Aubert, John-David; Bernasconi, Eric; Tissot, Adrien; Pison, Christophe; Nicod, Laurent; Boissel, Jean-Pierre; Magnan, Antoine

    2016-09-01

    Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. Chronic lung allograft dysfunction manifests as bronchiolitis obliterans syndrome or the recently described restrictive allograft syndrome. Although numerous risk factors have been identified so far, the physiopathological mechanisms of CLAD remain poorly understood. We investigate here the immune mechanisms involved in the development of CLAD after lung transplantation. We explore the innate or adaptive immune reactions induced by the allograft itself or by the environment and how they lead to allograft dysfunction. Because current literature suggests bronchiolitis obliterans syndrome and restrictive allograft syndrome as 2 distinct entities, we focus on the specific factors behind one or the other syndromes. Chronic lung allograft dysfunction is a multifactorial disease that remains irreversible and unpredictable so far. We thus finally discuss the potential of systems-biology approach to predict its occurrence and to better understand its underlying mechanisms.

  8. Mummified precocial bird wings in mid-Cretaceous Burmese amber

    PubMed Central

    Xing, Lida; McKellar, Ryan C.; Wang, Min; Bai, Ming; O'Connor, Jingmai K.; Benton, Michael J.; Zhang, Jianping; Wang, Yan; Tseng, Kuowei; Lockley, Martin G.; Li, Gang; Zhang, Weiwei; Xu, Xing

    2016-01-01

    Our knowledge of Cretaceous plumage is limited by the fossil record itself: compression fossils surrounding skeletons lack the finest morphological details and seldom preserve visible traces of colour, while discoveries in amber have been disassociated from their source animals. Here we report the osteology, plumage and pterylosis of two exceptionally preserved theropod wings from Burmese amber, with vestiges of soft tissues. The extremely small size and osteological development of the wings, combined with their digit proportions, strongly suggests that the remains represent precocial hatchlings of enantiornithine birds. These specimens demonstrate that the plumage types associated with modern birds were present within single individuals of Enantiornithes by the Cenomanian (99 million years ago), providing insights into plumage arrangement and microstructure alongside immature skeletal remains. This finding brings new detail to our understanding of infrequently preserved juveniles, including the first concrete examples of follicles, feather tracts and apteria in Cretaceous avialans. PMID:27352215

  9. Post-supereruption recovery at Toba Caldera

    NASA Astrophysics Data System (ADS)

    Mucek, Adonara E.; Danišík, Martin; de Silva, Shanaka L.; Schmitt, Axel K.; Pratomo, Indyo; Coble, Matthew A.

    2017-05-01

    Large calderas, or supervolcanoes, are sites of the most catastrophic and hazardous events on Earth, yet the temporal details of post-supereruption activity, or resurgence, remain largely unknown, limiting our ability to understand how supervolcanoes work and address their hazards. Toba Caldera, Indonesia, caused the greatest volcanic catastrophe of the last 100 kyr, climactically erupting ~74 ka. Since the supereruption, Toba has been in a state of resurgence but its magmatic and uplift history has remained unclear. Here we reveal that new 14C, zircon U-Th crystallization and (U-Th)/He ages show resurgence commenced at 69.7+/-4.5 ka and continued until at least ~2.7 ka, progressing westward across the caldera, as reflected by post-caldera effusive lava eruptions and uplifted lake sediment. The major stratovolcano north of Toba, Sinabung, shows strong geochemical kinship with Toba, and zircons from recent eruption products suggest Toba's climactic magma reservoir extends beneath Sinabung and is being tapped during eruptions.

  10. Overtraining Syndrome

    PubMed Central

    Kreher, Jeffrey B.; Schwartz, Jennifer B.

    2012-01-01

    Context: Fatigue and underperformance are common in athletes. Understanding overtraining syndrome (OTS) is helpful in the evaluation, management, and education of athletes. Evidence Acquisition: Relevant articles in English were searched with OVID (1948-2011) and PubMed using the following keywords: overtraining syndrome, overtraining, overreaching, unexplained underperformance, staleness, pathophysiology, management, treatment, evaluation. Bibliographies were reviewed for additional resources. Results: OTS appears to be a maladapted response to excessive exercise without adequate rest, resulting in perturbations of multiple body systems (neurologic, endocrinologic, immunologic) coupled with mood changes. Many hypotheses of OTS pathogenesis are reviewed, and a clinical approach to athletes with possible OTS (including history, testing, and prevention) is presented. Conclusions: OTS remains a clinical diagnosis with arbitrary definitions per the European College of Sports Science’s position statement. History and, in most situations, limited serologies are helpful. However, much remains to be learned given that most past research has been on athletes with overreaching rather than OTS. PMID:23016079

  11. Mummified precocial bird wings in mid-Cretaceous Burmese amber.

    PubMed

    Xing, Lida; McKellar, Ryan C; Wang, Min; Bai, Ming; O'Connor, Jingmai K; Benton, Michael J; Zhang, Jianping; Wang, Yan; Tseng, Kuowei; Lockley, Martin G; Li, Gang; Zhang, Weiwei; Xu, Xing

    2016-06-28

    Our knowledge of Cretaceous plumage is limited by the fossil record itself: compression fossils surrounding skeletons lack the finest morphological details and seldom preserve visible traces of colour, while discoveries in amber have been disassociated from their source animals. Here we report the osteology, plumage and pterylosis of two exceptionally preserved theropod wings from Burmese amber, with vestiges of soft tissues. The extremely small size and osteological development of the wings, combined with their digit proportions, strongly suggests that the remains represent precocial hatchlings of enantiornithine birds. These specimens demonstrate that the plumage types associated with modern birds were present within single individuals of Enantiornithes by the Cenomanian (99 million years ago), providing insights into plumage arrangement and microstructure alongside immature skeletal remains. This finding brings new detail to our understanding of infrequently preserved juveniles, including the first concrete examples of follicles, feather tracts and apteria in Cretaceous avialans.

  12. Rapid freezing of water under dynamic compression

    NASA Astrophysics Data System (ADS)

    Myint, Philip C.; Belof, Jonathan L.

    2018-06-01

    Understanding the behavior of materials at extreme pressures is a central issue in fields like aerodynamics, astronomy, and geology, as well as for advancing technological grand challenges such as inertial confinement fusion. Dynamic compression experiments to probe high-pressure states often encounter rapid phase transitions that may cause the materials to behave in unexpected ways, and understanding the kinetics of these phase transitions remains an area of great interest. In this review, we examine experimental and theoretical/computational efforts to study the freezing kinetics of water to a high-pressure solid phase known as ice VII. We first present a detailed analysis of dynamic compression experiments in which water has been observed to freeze on sub-microsecond time scales to ice VII. This is followed by a discussion of the limitations of currently available molecular and continuum simulation methods in modeling these experiments. We then describe how our phase transition kinetics models, which are based on classical nucleation theory, provide a more physics-based framework that overcomes some of these limitations. Finally, we give suggestions on future experimental and modeling work on the liquid–ice VII transition, including an outline of the development of a predictive multiscale model in which molecular and continuum simulations are intimately coupled.

  13. Distinct management issues with Crohn's disease of the small intestine.

    PubMed

    Fong, Steven C M; Irving, Peter M

    2015-03-01

    Small bowel Crohn's disease can present with clinical challenges that are specific to its location. In this review, we address some of the areas that present particular problems in small bowel Crohn's disease. A key issue specific to small bowel Crohn's disease relates to its diagnosis given that access to the small bowel is limited. Radiological advances, particularly in small bowel ultrasonography and MRI, as well as the introduction of capsule endoscopy and balloon enteroscopy are helping to address this. In addition, our ability to differentiate small bowel Crohn's disease from other causes of inflammation, such as tuberculosis, is improving on the basis of better understanding of the features that differentiate these conditions. It is also becoming apparent that jejunal Crohn's disease represents a distinct disease phenotype with potentially worse clinical outcomes. Finally, because it is a rare complication, our understanding of small bowel cancer associated with Crohn's disease remains limited. Recent publications are, however, starting to improve our knowledge of this condition. Although small bowel Crohn's disease presents specific management issues not seen in patients with Crohn's disease elsewhere in the gastrointestinal tract, our knowledge of how to manage these is improving.

  14. Adverse effects of perinatal nicotine exposure on reproductive outcomes.

    PubMed

    Wong, Michael K; Barra, Nicole G; Alfaidy, Nadia; Hardy, Daniel B; Holloway, Alison C

    2015-12-01

    Nicotine exposure during pregnancy through cigarette smoking, nicotine replacement therapies or e-cigarette use continues to be a widespread public health problem, impacting both fetal and postnatal health. Yet, at this time, there remains limited data regarding the safety and efficacy in using these nicotine products during pregnancy. Notably, reports assessing the effect of nicotine exposure on postnatal health outcomes in humans, including reproductive health, are severely lacking. Our current understanding regarding the consequences of nicotine exposure during pregnancy is limited to a few animal studies, which do not comprehensively address the underlying cellular mechanisms involved. This paper aims to critically review the current knowledge from human and animal studies regarding the direct and indirect effects (e.g. obesity) of maternal nicotine exposure, regardless of its source, on reproductive outcomes in pregnancy and postnatal life. Furthermore, this review highlights several key cellular mechanisms involved in these adverse reproductive deficits including oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. By understanding the interplay of the cellular mechanisms involved, further strategies could be developed to prevent the reproductive abnormalities resulting from exposure to nicotine in utero and influence informed clinical guidelines for pregnant women. © 2015 Society for Reproduction and Fertility.

  15. Rapid freezing of water under dynamic compression.

    PubMed

    Myint, Philip C; Belof, Jonathan L

    2018-06-13

    Understanding the behavior of materials at extreme pressures is a central issue in fields like aerodynamics, astronomy, and geology, as well as for advancing technological grand challenges such as inertial confinement fusion. Dynamic compression experiments to probe high-pressure states often encounter rapid phase transitions that may cause the materials to behave in unexpected ways, and understanding the kinetics of these phase transitions remains an area of great interest. In this review, we examine experimental and theoretical/computational efforts to study the freezing kinetics of water to a high-pressure solid phase known as ice VII. We first present a detailed analysis of dynamic compression experiments in which water has been observed to freeze on sub-microsecond time scales to ice VII. This is followed by a discussion of the limitations of currently available molecular and continuum simulation methods in modeling these experiments. We then describe how our phase transition kinetics models, which are based on classical nucleation theory, provide a more physics-based framework that overcomes some of these limitations. Finally, we give suggestions on future experimental and modeling work on the liquid-ice VII transition, including an outline of the development of a predictive multiscale model in which molecular and continuum simulations are intimately coupled.

  16. Movement concepts approach in studies on flamenco dancing: A systematic review.

    PubMed

    Forczek, Wanda; Baena-Chicón, Irene; Vargas-Macías, Alfonso

    2017-10-01

    Flamenco is a highly emotional and demanding dance form. It is important to understand how the dancer's body works in order to improve fitness levels and reduce injuries. Thus, our investigation reviewed studies on kinesiological aspects of flamenco over recent years. The review was restricted to experimental studies. Literature searches were conducted using the following databases: PubMed, Scopus, and Ebsco: SPORTDiscus with Full Text, Medline, Health Source: Nursing/Academic Edition, Health Source - Consumer Edition. After limiting the search, 180 potential articles remained for analysis. A total of 27 papers on different aspects of flamenco dance were finally selected: biomechanics (14), podiatry (6), injury incidence (3), anthropometry (2), and physiology (2). These studies have applied well-established methods from sports studies. However, we noted a number of potential limitations when applied to flamenco. The evidence from this review shows that flamenco dancing demands high levels of effort. Further research is required to understand how the dancer's body works in order to improve fitness levels and reduce injuries. Most of the results presented here are consistent among studies. However, there is a great scarcity of research addressing flamenco movement in a more comprehensive perspective.

  17. How do mental health practitioners operationalise cultural competency in everyday practice? A qualitative analysis.

    PubMed

    Mollah, Tooba Noor; Antoniades, Josefine; Lafeer, Fathima Ijaza; Brijnath, Bianca

    2018-06-20

    Despite continued policy and research emphasis to deliver culturally competent mental healthcare, there is: (1) limited evidence about what frontline practitioners consider to be culturally competent care and; (2) what helps or hinders them in delivering such care in their everyday practice. The aims of this article are to address these gaps. Qualitative in-depth interviews were conducted with 20 mental health practitioners working with immigrant patients to explore their understandings and experiences of culturally competent care. Interviews were conducted between September 2015 and February 2016 in the state of Victoria, Australia. Data were thematically analysed. There were common understandings of cultural competence but its operationalisation differed by profession, health setting, locality, and years of experience; urban psychiatrists were more functional in their approach and authoritarian in their communication with patients compared to allied health staff in non-specialist mental health settings, in rural areas, with less years of experience. Different methods of operationalising cultural competence translated into complex ways of building cultural concordance with patients, also influenced by health practitioners' own cultural background and cultural exposures. Limited access to interpreters and organisational apathy remain barriers to promoting cultural competency whereas organisational support, personal motivation, and professional resilience remain critical facilitators to sustaining cultural competency in everyday practice. While there is need for widespread cultural competence teaching to all mental health professionals, this training must be specific to different professional needs, health settings, and localities of practice (rural or urban). Experiential teaching at tertiary level or professional development programs may provide an avenue to improve the status quo but a 'one-size-fits-all' model is unlikely to work.

  18. The long (LINEs) and the short (SINEs) of it: altered methylation as a precursor to toxicity.

    PubMed

    Carnell, Ammie N; Goodman, Jay I

    2003-10-01

    Although once thought of as "junk" DNA, the importance of interspersed elements in the genome has become increasingly appreciated in recent years. In a broad sense these are collectively referred to as transposable elements, which encompass both transposons and retrotransposons. The latter include long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs). Expression of these elements leads to genetic instability. Therefore, it is important that they remain transcriptionally silenced, and DNA methylation plays a key role in this regard. A framework for understanding the possible interplay between altered DNA methylation, an epigenetic change, and mutational events is presented. A case is made as to how retrotransposable elements, specifically LINEs and SINEs, are likely to emerge as key players in furthering our understanding of mechanisms underlying a variety of toxicities, including carcinogenesis but not limited to this endpoint.

  19. Inflammatory bowel disease pathogenesis: where are we?

    PubMed

    Fiocchi, Claudio

    2015-03-01

    Inflammatory bowel disease (IBD) is presently one of the most investigated human disorders. Expansion of knowledge of its pathophysiology has helped in developing novel medications to combat gut inflammation with a considerably degree of success. Despite this progress, much more remains to be done in regard to gaining a more profound understanding of IBD pathogenesis, detecting inflammation before it clinically manifests, implementing lifestyle modifications, and developing agents that can modify the natural course of the disease. One of the limitations to achieve these goals is the lack of integration of the major components of IBD pathogenesis, that is the exposome, the genome, the gut microbiome, and the immunome. An "IBD integrome" approach that takes advantage of all functional information derived from the detailed investigation of each single pathogenic component through the use of systems biology may offer the solution to understand IBD and cure it. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  20. Brittle and ductile friction and the physics of tectonic tremor

    USGS Publications Warehouse

    Daub, Eric G.; Shelly, David R.; Guyer, Robert A.; Johnson, P.A.

    2011-01-01

    Observations of nonvolcanic tremor provide a unique window into the mechanisms of deformation and failure in the lower crust. At increasing depths, rock deformation gradually transitions from brittle, where earthquakes occur, to ductile, with tremor occurring in the transitional region. The physics of deformation in the transition region remain poorly constrained, limiting our basic understanding of tremor and its relation to earthquakes. We combine field and laboratory observations with a physical friction model comprised of brittle and ductile components, and use the model to provide constraints on the friction and stress state in the lower crust. A phase diagram is constructed that characterizes under what conditions all faulting behaviors occur, including earthquakes, tremor, silent transient slip, and steady sliding. Our results show that tremor occurs over a range of ductile and brittle frictional strengths, and advances our understanding of the physical conditions at which tremor and earthquakes take place.

  1. The contributions of cognitive neuroscience and neuroimaging to understanding mechanisms of behavior change in addiction.

    PubMed

    Morgenstern, Jon; Naqvi, Nasir H; Debellis, Robert; Breiter, Hans C

    2013-06-01

    In the last decade, there has been an upsurge of interest in understanding the mechanisms of behavior change (MOBC) and effective behavioral interventions as a strategy to improve addiction-treatment efficacy. However, there remains considerable uncertainty about how treatment research should proceed to address the MOBC issue. In this article, we argue that limitations in the underlying models of addiction that inform behavioral treatment pose an obstacle to elucidating MOBC. We consider how advances in the cognitive neuroscience of addiction offer an alternative conceptual and methodological approach to studying the psychological processes that characterize addiction, and how such advances could inform treatment process research. In addition, we review neuroimaging studies that have tested aspects of neurocognitive theories as a strategy to inform addiction therapies and discuss future directions for transdisciplinary collaborations across cognitive neuroscience and MOBC research. 2013 APA, all rights reserved

  2. Change in the magnitude and mechanisms of global temperature variability with warming.

    PubMed

    Brown, Patrick T; Ming, Yi; Li, Wenhong; Hill, Spencer A

    2017-01-01

    Natural unforced variability in global mean surface air temperature (GMST) can mask or exaggerate human-caused global warming, and thus a complete understanding of this variability is highly desirable. Significant progress has been made in elucidating the magnitude and physical origins of present-day unforced GMST variability, but it has remained unclear how such variability may change as the climate warms. Here we present modeling evidence that indicates that the magnitude of low-frequency GMST variability is likely to decline in a warmer climate and that its generating mechanisms may be fundamentally altered. In particular, a warmer climate results in lower albedo at high latitudes, which yields a weaker albedo feedback on unforced GMST variability. These results imply that unforced GMST variability is dependent on the background climatological conditions, and thus climate model control simulations run under perpetual preindustrial conditions may have only limited relevance for understanding the unforced GMST variability of the future.

  3. Advancing understanding of executive function impairments and psychopathology: bridging the gap between clinical and cognitive approaches

    PubMed Central

    Snyder, Hannah R.; Miyake, Akira; Hankin, Benjamin L.

    2015-01-01

    Executive function (EF) is essential for successfully navigating nearly all of our daily activities. Of critical importance for clinical psychological science, EF impairments are associated with most forms of psychopathology. However, despite the proliferation of research on EF in clinical populations, with notable exceptions clinical and cognitive approaches to EF have remained largely independent, leading to failures to apply theoretical and methodological advances in one field to the other field and hindering progress. First, we review the current state of knowledge of EF impairments associated with psychopathology and limitations to the previous research in light of recent advances in understanding and measuring EF. Next, we offer concrete suggestions for improving EF assessment. Last, we suggest future directions, including integrating modern models of EF with state of the art, hierarchical models of dimensional psychopathology as well as translational implications of EF-informed research on clinical science. PMID:25859234

  4. Researching a local heroin market as a complex adaptive system.

    PubMed

    Hoffer, Lee D; Bobashev, Georgiy; Morris, Robert J

    2009-12-01

    This project applies agent-based modeling (ABM) techniques to better understand the operation, organization, and structure of a local heroin market. The simulation detailed was developed using data from an 18-month ethnographic case study. The original research, collected in Denver, CO during the 1990s, represents the historic account of users and dealers who operated in the Larimer area heroin market. Working together, the authors studied the behaviors of customers, private dealers, street-sellers, brokers, and the police, reflecting the core elements pertaining to how the market operated. After evaluating the logical consistency between the data and agent behaviors, simulations scaled-up interactions to observe their aggregated outcomes. While the concept and findings from this study remain experimental, these methods represent a novel way in which to understand illicit drug markets and the dynamic adaptations and outcomes they generate. Extensions of this research perspective, as well as its strengths and limitations, are discussed.

  5. Framework for Advancing the Reporting of Patient Engagement in Rheumatology Research Projects.

    PubMed

    Hamilton, Clayon B; Leese, Jenny C; Hoens, Alison M; Li, Linda C

    2017-07-01

    The term "patient engagement in research" refers to patients and their surrogates undertaking roles in the research process beyond those of study participants. This paper proposes a new framework for describing patient engagement in research, based on analysis of 30 publications related to patient engagement. Over the past 15 years, patients' perspectives have been instrumental in broadening the scope of rheumatology research and outcome measurement, such as evaluating fatigue in rheumatoid arthritis. Recent reviews, however, highlight low-quality reporting of patient engagement in research. Until we have more detailed information about patient engagement in rheumatology research, our understanding of how patients' perspectives are being integrated into research projects remains limited. When authors follow our guidance on the important components for describing patients' roles and function as "research partners," researchers and other knowledge users will better understand how patients' perspectives were integrated in their research projects.

  6. The Lived Experience of Black Nurse Faculty in Predominantly White Schools of Nursing.

    PubMed

    Whitfield-Harris, Lisa; Lockhart, Joan Such; Zoucha, Richard; Alexander, Rumay

    2017-03-01

    This study explored the experiences of Black nurse faculty employed in predominantly White schools of nursing. High attrition rates of this group were noted in previous literature. Understanding their experiences is important to increase nurse diversity. Hermeneutic phenomenology was used to explore the experiences of 15 Black nurse faculty using interviews. Four themes were extracted as the following: cultural norms of the workplace, coping with improper assets, life as a "Lone Ranger," and surviving the workplace environment. The study provided insight to understand the meaning that Black faculty members give to their experiences working in predominantly White schools of nursing. Findings exemplify the need to improve culturally competent work environments and mentoring programs. Results suggest that better communication and proper respect from students, colleagues, and administrators are necessary. The limited research on this topic illustrates that Black nurse faculty remain under investigated; research is necessary to determine effective change strategies.

  7. The Contributions of Cognitive Neuroscience and Neuroimaging to Understanding Mechanisms of Behavior Change in Addiction

    PubMed Central

    Morgenstern, Jon; Naqvi, Nasir H.; Debellis, Robert; Breiter, Hans C.

    2013-01-01

    In the last decade, there has been an upsurge of interest in understanding the mechanisms of behavior change (MOBC) and effective behavioral interventions as a strategy to improve addiction-treatment efficacy. However, there remains considerable uncertainty about how treatment research should proceed to address the MOBC issue. In this article, we argue that limitations in the underlying models of addiction that inform behavioral treatment pose an obstacle to elucidating MOBC. We consider how advances in the cognitive neuroscience of addiction offer an alternative conceptual and methodological approach to studying the psychological processes that characterize addiction, and how such advances could inform treatment process research. In addition, we review neuroimaging studies that have tested aspects of neurocognitive theories as a strategy to inform addiction therapies and discuss future directions for transdisciplinary collaborations across cognitive neuroscience and MOBC research. PMID:23586452

  8. A genomic approach to identify hybrid incompatibility genes.

    PubMed

    Cooper, Jacob C; Phadnis, Nitin

    2016-07-02

    Uncovering the genetic and molecular basis of barriers to gene flow between populations is key to understanding how new species are born. Intrinsic postzygotic reproductive barriers such as hybrid sterility and hybrid inviability are caused by deleterious genetic interactions known as hybrid incompatibilities. The difficulty in identifying these hybrid incompatibility genes remains a rate-limiting step in our understanding of the molecular basis of speciation. We recently described how whole genome sequencing can be applied to identify hybrid incompatibility genes, even from genetically terminal hybrids. Using this approach, we discovered a new hybrid incompatibility gene, gfzf, between Drosophila melanogaster and Drosophila simulans, and found that it plays an essential role in cell cycle regulation. Here, we discuss the history of the hunt for incompatibility genes between these species, discuss the molecular roles of gfzf in cell cycle regulation, and explore how intragenomic conflict drives the evolution of fundamental cellular mechanisms that lead to the developmental arrest of hybrids.

  9. Large-Scale Experimental Planetary Science Meets Planetary Defense: Deorbiting an Asteroidal Satellite

    NASA Technical Reports Server (NTRS)

    Cintala, M. J.; Durda, D. D.; Housen, K. R.

    2005-01-01

    Other than remote-sensing and spacecraft-derived data, the only information that exists regarding the physical and chemical properties of asteroids is that inferred through calculations, numerical simulations, extrapolation of experiments, and meteorite studies. Our understanding of the dynamics of accretion of planetesimals, collisional disruption of asteroids, and the macroscopic, shock-induced modification of the surfaces of such small objects is also, for the most part, founded on similar inferences. While considerable strides have been made in improving the state of asteroid science, too many unknowns remain to assert that we understand the parameters necessary for the more practical problem of deflecting an asteroid or asteroid pair on an Earth-intersecting trajectory. Many of these deficiencies could be reduced or eliminated by intentionally deorbiting an asteroidal satellite and monitoring the resulting collision between it and the primary asteroid, a capability that is well within the limitations of current technology.

  10. From sensation to perception: Using multivariate classification of visual illusions to identify neural correlates of conscious awareness in space and time.

    PubMed

    Hogendoorn, Hinze

    2015-01-01

    An important goal of cognitive neuroscience is understanding the neural underpinnings of conscious awareness. Although the low-level processing of sensory input is well understood in most modalities, it remains a challenge to understand how the brain translates such input into conscious awareness. Here, I argue that the application of multivariate pattern classification techniques to neuroimaging data acquired while observers experience perceptual illusions provides a unique way to dissociate sensory mechanisms from mechanisms underlying conscious awareness. Using this approach, it is possible to directly compare patterns of neural activity that correspond to the contents of awareness, independent from changes in sensory input, and to track these neural representations over time at high temporal resolution. I highlight five recent studies using this approach, and provide practical considerations and limitations for future implementations.

  11. Mechanism for rapid growth of organic–inorganic halide perovskite crystals

    PubMed Central

    Nayak, Pabitra K.; Moore, David T.; Wenger, Bernard; Nayak, Simantini; Haghighirad, Amir A.; Fineberg, Adam; Noel, Nakita K.; Reid, Obadiah G.; Rumbles, Garry; Kukura, Philipp; Vincent, Kylie A.; Snaith, Henry J.

    2016-01-01

    Optoelectronic devices based on hybrid halide perovskites have shown remarkable progress to high performance. However, despite their apparent success, there remain many open questions about their intrinsic properties. Single crystals are often seen as the ideal platform for understanding the limits of crystalline materials, and recent reports of rapid, high-temperature crystallization of single crystals should enable a variety of studies. Here we explore the mechanism of this crystallization and find that it is due to reversible changes in the solution where breaking up of colloids, and a change in the solvent strength, leads to supersaturation and subsequent crystallization. We use this knowledge to demonstrate a broader range of processing parameters and show that these can lead to improved crystal quality. Our findings are therefore of central importance to enable the continued advancement of perovskite optoelectronics and to the improved reproducibility through a better understanding of factors influencing and controlling crystallization. PMID:27830749

  12. Change in the Magnitude and Mechanisms of Global Temperature Variability with Warming

    NASA Astrophysics Data System (ADS)

    Brown, P. T.; Ming, Y.; Li, W.; Hill, S. A.

    2017-12-01

    Natural unforced variability in global mean surface air temperature (GMST) can mask or exaggerate human-caused global warming, and thus a complete understanding of this variability is highly desirable. Significant progress has been made in elucidating the magnitude and physical origins of present-day unforced GMST variability, but it has remained unclear how such variability may change as the climate warms. Here we present modeling evidence that indicates that the magnitude of low-frequency GMST variability is likely to decline in a warmer climate and that its generating mechanisms may be fundamentally altered. In particular, a warmer climate results in lower albedo at high latitudes, which yields a weaker albedo feedback on unforced GMST variability. These results imply that unforced GMST variability is dependent on the background climatological conditions, and thus climate model control simulations run under perpetual preindustrial conditions may have only limited relevance for understanding the unforced GMST variability of the future.

  13. A novel and rapid method for obtaining high titre intact prion strains from mammalian brain.

    PubMed

    Wenborn, Adam; Terry, Cassandra; Gros, Nathalie; Joiner, Susan; D'Castro, Laura; Panico, Silvia; Sells, Jessica; Cronier, Sabrina; Linehan, Jacqueline M; Brandner, Sebastian; Saibil, Helen R; Collinge, John; Wadsworth, Jonathan D F

    2015-05-07

    Mammalian prions exist as multiple strains which produce characteristic and highly reproducible phenotypes in defined hosts. How this strain diversity is encoded by a protein-only agent remains one of the most interesting and challenging questions in biology with wide relevance to understanding other diseases involving the aggregation or polymerisation of misfolded host proteins. Progress in understanding mammalian prion strains has however been severely limited by the complexity and variability of the methods used for their isolation from infected tissue and no high resolution structures have yet been reported. Using high-throughput cell-based prion bioassay to re-examine prion purification from first principles we now report the isolation of prion strains to exceptional levels of purity from small quantities of infected brain and demonstrate faithful retention of biological and biochemical strain properties. The method's effectiveness and simplicity should facilitate its wide application and expedite structural studies of prions.

  14. A novel and rapid method for obtaining high titre intact prion strains from mammalian brain

    PubMed Central

    Wenborn, Adam; Terry, Cassandra; Gros, Nathalie; Joiner, Susan; D’Castro, Laura; Panico, Silvia; Sells, Jessica; Cronier, Sabrina; Linehan, Jacqueline M.; Brandner, Sebastian; Saibil, Helen R.; Collinge, John; Wadsworth, Jonathan D. F.

    2015-01-01

    Mammalian prions exist as multiple strains which produce characteristic and highly reproducible phenotypes in defined hosts. How this strain diversity is encoded by a protein-only agent remains one of the most interesting and challenging questions in biology with wide relevance to understanding other diseases involving the aggregation or polymerisation of misfolded host proteins. Progress in understanding mammalian prion strains has however been severely limited by the complexity and variability of the methods used for their isolation from infected tissue and no high resolution structures have yet been reported. Using high-throughput cell-based prion bioassay to re-examine prion purification from first principles we now report the isolation of prion strains to exceptional levels of purity from small quantities of infected brain and demonstrate faithful retention of biological and biochemical strain properties. The method’s effectiveness and simplicity should facilitate its wide application and expedite structural studies of prions. PMID:25950908

  15. Known knowns, known unknowns and unknown unknowns in prokaryotic transposition.

    PubMed

    Siguier, Patricia; Gourbeyre, Edith; Chandler, Michael

    2017-08-01

    Although the phenomenon of transposition has been known for over 60 years, its overarching importance in modifying and streamlining genomes took some time to recognize. In spite of a robust understanding of transposition of some TE, there remain a number of important TE groups with potential high genome impact and unknown transposition mechanisms and yet others, only recently identified by bioinformatics, yet to be formally confirmed as mobile. Here, we point to some areas of limited understanding concerning well established important TE groups with DDE Tpases, to address central gaps in our knowledge of characterised Tn with other types of Tpases and finally, to highlight new potentially mobile DNA species. It is not exhaustive. Examples have been chosen to provide encouragement in the continued exploration of the considerable prokaryotic mobilome especially in light of the current threat to public health posed by the spread of multiple Ab R . Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Tectonic control on the persistence of glacially sculpted topography

    PubMed Central

    Prasicek, Günther; Larsen, Isaac J.; Montgomery, David R.

    2015-01-01

    One of the most fundamental insights for understanding how landscapes evolve is based on determining the extent to which topography was shaped by glaciers or by rivers. More than 104 years after the last major glaciation the topography of mountain ranges worldwide remains dominated by characteristic glacial landforms such as U-shaped valleys, but an understanding of the persistence of such landforms is lacking. Here we use digital topographic data to analyse valley shapes at sites worldwide to demonstrate that the persistence of U-shaped valleys is controlled by the erosional response to tectonic forcing. Our findings indicate that glacial topography in Earth's most rapidly uplifting mountain ranges is rapidly replaced by fluvial topography and hence valley forms do not reflect the cumulative action of multiple glacial periods, implying that the classic physiographic signature of glaciated landscapes is best expressed in, and indeed limited by, the extent of relatively low-uplift terrain. PMID:26271245

  17. A prior-based integrative framework for functional transcriptional regulatory network inference

    PubMed Central

    Siahpirani, Alireza F.

    2017-01-01

    Abstract Transcriptional regulatory networks specify regulatory proteins controlling the context-specific expression levels of genes. Inference of genome-wide regulatory networks is central to understanding gene regulation, but remains an open challenge. Expression-based network inference is among the most popular methods to infer regulatory networks, however, networks inferred from such methods have low overlap with experimentally derived (e.g. ChIP-chip and transcription factor (TF) knockouts) networks. Currently we have a limited understanding of this discrepancy. To address this gap, we first develop a regulatory network inference algorithm, based on probabilistic graphical models, to integrate expression with auxiliary datasets supporting a regulatory edge. Second, we comprehensively analyze our and other state-of-the-art methods on different expression perturbation datasets. Networks inferred by integrating sequence-specific motifs with expression have substantially greater agreement with experimentally derived networks, while remaining more predictive of expression than motif-based networks. Our analysis suggests natural genetic variation as the most informative perturbation for network inference, and, identifies core TFs whose targets are predictable from expression. Multiple reasons make the identification of targets of other TFs difficult, including network architecture and insufficient variation of TF mRNA level. Finally, we demonstrate the utility of our inference algorithm to infer stress-specific regulatory networks and for regulator prioritization. PMID:27794550

  18. Inspiration for wing design: how forelimb specialization enables active flight in modern vertebrates

    PubMed Central

    2017-01-01

    Harnessing flight strategies refined by millions of years of evolution can help expedite the design of more efficient, manoeuvrable and robust flying robots. This review synthesizes recent advances and highlights remaining gaps in our understanding of how bird and bat wing adaptations enable effective flight. Included in this discussion is an evaluation of how current robotic analogues measure up to their biological sources of inspiration. Studies of vertebrate wings have revealed skeletal systems well suited for enduring the loads required during flight, but the mechanisms that drive coordinated motions between bones and connected integuments remain ill-described. Similarly, vertebrate flight muscles have adapted to sustain increased wing loading, but a lack of in vivo studies limits our understanding of specific muscular functions. Forelimb adaptations diverge at the integument level, but both bird feathers and bat membranes yield aerodynamic surfaces with a level of robustness unparalleled by engineered wings. These morphological adaptations enable a diverse range of kinematics tuned for different flight speeds and manoeuvres. By integrating vertebrate flight specializations—particularly those that enable greater robustness and adaptability—into the design and control of robotic wings, engineers can begin narrowing the wide margin that currently exists between flying robots and vertebrates. In turn, these robotic wings can help biologists create experiments that would be impossible in vivo. PMID:28592663

  19. Understanding death with limited experience in life: dying children's and adolescents' understanding of their own terminal illness and death.

    PubMed

    Bates, Alan T; Kearney, Julia A

    2015-03-01

    An up-to-date summary of the literature on children's and adolescents' understanding of their own terminal illness and death. Clinicians still find it difficult to speak with pediatric patients about death even though guidelines for facilitating communication on the topic exist. As a result, pediatric patients are less likely to develop a clear understanding of their illness and there is a disconnect between clinicians and parents about prognosis, even when clinicians have concluded there is no longer possibility for cure. Insufficient communication and poor understanding may increase the risk of patients feeling isolated, mistrustful and anxious, and deprive them of a role model who can communicate about painful issues or share difficult feelings. Despite these complexities, young people often show remarkable resiliency in the face of death and want to get the most out of the remaining time they have. In addition to these most recent findings, this review examines the challenges in researching this topic, obstacles to patients receiving information about prognosis, and how physical symptoms affect patients' ability to develop an understanding. It also reviews sources of insight into pediatric patients' understanding including the development of concepts of death, fears about their own death, legal interpretations of what patients understand, and how terminally ill young people continue to treasure life. It concludes by addressing ways clinicians can use the knowledge we have to communicate well with dying children and adolescents and their families.

  20. A health literacy and usability heuristic evaluation of a mobile consumer health application.

    PubMed

    Monkman, Helen; Kushniruk, Andre

    2013-01-01

    Usability and health literacy are two critical factors in the design and evaluation of consumer health information systems. However, methods for evaluating these two factors in conjunction remain limited. This study adapted a set of existing guidelines for the design of consumer health Web sites into evidence-based evaluation heuristics tailored specifically for mobile consumer health applications. In order to test the approach, a mobile consumer health application (app) was then evaluated using these heuristics. In addition to revealing ways to improve the usability of the system, this analysis identified opportunities to augment the content to make it more understandable by users with limited health literacy. This study successfully demonstrated the utility of converting existing design guidelines into heuristics for the evaluation of usability and health literacy. The heuristics generated could be applied for assessing and revising other existing consumer health information systems.

  1. Recent developments in machine learning applications in landslide susceptibility mapping

    NASA Astrophysics Data System (ADS)

    Lun, Na Kai; Liew, Mohd Shahir; Matori, Abdul Nasir; Zawawi, Noor Amila Wan Abdullah

    2017-11-01

    While the prediction of spatial distribution of potential landslide occurrences is a primary interest in landslide hazard mitigation, it remains a challenging task. To overcome the scarceness of complete, sufficiently detailed geomorphological attributes and environmental conditions, various machine-learning techniques are increasingly applied to effectively map landslide susceptibility for large regions. Nevertheless, limited review papers are devoted to this field, particularly on the various domain specific applications of machine learning techniques. Available literature often report relatively good predictive performance, however, papers discussing the limitations of each approaches are quite uncommon. The foremost aim of this paper is to narrow these gaps in literature and to review up-to-date machine learning and ensemble learning techniques applied in landslide susceptibility mapping. It provides new readers an introductory understanding on the subject matter and researchers a contemporary review of machine learning advancements alongside the future direction of these techniques in the landslide mitigation field.

  2. On the Reprocessing and Reanalysis of Observations for Climate

    NASA Technical Reports Server (NTRS)

    Bosilovich, Michael G.; Kennedy, John; Dee, Dick; ONeill, Alan

    2012-01-01

    The long observational record is critical to our understanding of the Earth s climate, but most observing systems were not developed with a climate objective in mind. As a result, tremendous efforts have gone into assessing and reprocessing the data records to improve their usefulness in climate studies. Many challenges remain, such as tracking the improvement of processing algorithms and limited spatial coverage. Reanalyses have fostered significant research, yet reliable global trends in many physical fields are not yet attainable, despite significant advances in data assimilation and numerical modeling. Communication of the strengths, limitations and uncertainties of reprocessed observations and reanalysis data, not only among the community of developers, but also with the extended research community, including the new generations of researchers and the decision makers is crucial for further advancement of the observational data records. WCRP provides the means to bridge the different motivating objectives on which national efforts focus.

  3. Whole-Brain Microscopy Meets In Vivo Neuroimaging: Techniques, Benefits, and Limitations.

    PubMed

    Aswendt, Markus; Schwarz, Martin; Abdelmoula, Walid M; Dijkstra, Jouke; Dedeurwaerdere, Stefanie

    2017-02-01

    Magnetic resonance imaging, positron emission tomography, and optical imaging have emerged as key tools to understand brain function and neurological disorders in preclinical mouse models. They offer the unique advantage of monitoring individual structural and functional changes over time. What remained unsolved until recently was to generate whole-brain microscopy data which can be correlated to the 3D in vivo neuroimaging data. Conventional histological sections are inappropriate especially for neuronal tracing or the unbiased screening for molecular targets through the whole brain. As part of the European Society for Molecular Imaging (ESMI) meeting 2016 in Utrecht, the Netherlands, we addressed this issue in the Molecular Neuroimaging study group meeting. Presentations covered new brain clearing methods, light sheet microscopes for large samples, and automatic registration of microscopy to in vivo imaging data. In this article, we summarize the discussion; give an overview of the novel techniques; and discuss the practical needs, benefits, and limitations.

  4. The Research Consortium on Religious Healthcare Institutions: studying the impact of religious restrictions on women's reproductive health.

    PubMed

    Freedman, Lori R; Stulberg, Debra B

    2016-07-01

    Catholic hospitals and other religious institutions are a large and growing part of the US health care system. They have specific policies restricting reproductive health care. Despite increased public attention in the media to women denied necessary pregnancy-related care at Catholic hospitals, research on the effects of religious restrictions remains limited. This article summarizes research priorities as generated by 80 attendees at the inaugural meeting of the Research Consortium on Religious Healthcare Institutions. Such research is need to understand the impact of religious health system ownership on women's health. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Cancer metabolism: fatty acid oxidation in the limelight

    PubMed Central

    Carracedo, Arkaitz; Cantley, Lewis C.; Pandolfi, Pier Paolo

    2013-01-01

    Warburg suggested that the alterations in metabolism that he observed in cancer cells were due to the malfunction of mitochondria. In the past decade, we have revisited this idea and reached a better understanding of the ‘metabolic switch’ in cancer cells, including the intimate and causal relationship between cancer genes and metabolic alterations, and their potential to be targeted for cancer treatment. However, the vast majority of the research into cancer metabolism has been limited to a handful of metabolic pathways, while other pathways have remained in the dark. This Progress article brings to light the important contribution of fatty acid oxidation to cancer cell function. PMID:23446547

  6. Bolzano`s Approach to the Paradoxes of Infinity: Implications for Teaching

    NASA Astrophysics Data System (ADS)

    Waldegg, Guillermina

    2005-08-01

    In this paper we analyze excerpts of Paradoxes of the Infinite, the posthumous work of Bernard Bolzano (1781-1848), in order to show that Georg Cantor‘s (1845-1918) approach to the problem of defining actual mathematical infinity is not the most natural. In fact, Bolzano‘s approach to the paradoxes of infinity is more intuitive, while remaining internally coherent. Bolzano‘s approach, however, had limitations. We discuss implications for teaching, which include a better understanding of the responses of students to situations involving actual mathematical infinity, for it is possible to draw a kind of parallel between these responses and Bolzano‘s reasoning.

  7. Treatments for food allergy: how close are we?

    PubMed

    Wang, Julie; Sampson, Hugh A

    2012-12-01

    Food allergy continues to be a challenging health problem, with prevalence continuing to increase and anaphylaxis still an unpredictable possibility. While improvements in diagnosis are more accurately identifying affected individuals, treatment options remain limited. The cornerstone of treatment relies on strict avoidance of the offending allergens and education regarding management of allergic reactions. Despite vigilance in avoidance, accidental ingestions and reactions continue to occur. With recent advances in the understanding of humoral and cellular immune responses in food allergy and mechanisms of tolerance, several therapeutic strategies for food allergies are currently being investigated with the hopes of providing a cure or long-term remission from food allergy.

  8. Critical fictive temperature for plasticity in metallic glasses

    PubMed Central

    Kumar, Golden; Neibecker, Pascal; Liu, Yan Hui; Schroers, Jan

    2013-01-01

    A long-sought goal in metallic glasses is to impart ductility without conceding their strength and elastic limit. The rational design of tough metallic glasses, however, remains challenging because of the inability of existing theories to capture the correlation between plasticity, composition and processing for a wide range of glass-forming alloys. Here we propose a phenomenological criterion based on a critical fictive temperature, Tfc, which can rationalize the effect of composition, cooling rate and annealing on room-temperature plasticity of metallic glasses. Such criterion helps in understanding the widespread mechanical behaviour of metallic glasses and reveals alloy-specific preparation conditions to circumvent brittleness. PMID:23443564

  9. Chromatin assembly: Journey to the CENter of the chromosome

    PubMed Central

    Chen, Chin-Chi

    2016-01-01

    All eukaryotic genomes are packaged into basic units of DNA wrapped around histone proteins called nucleosomes. The ability of histones to specify a variety of epigenetic states at defined chromatin domains is essential for cell survival. The most distinctive type of chromatin is found at centromeres, which are marked by the centromere-specific histone H3 variant CENP-A. Many of the factors that regulate CENP-A chromatin have been identified; however, our understanding of the mechanisms of centromeric nucleosome assembly, maintenance, and reorganization remains limited. This review discusses recent insights into these processes and draws parallels between centromeric and noncentromeric chromatin assembly mechanisms. PMID:27377247

  10. Interface between intellectual disability and mental health: hermeneutic review.

    PubMed

    Surjus, Luciana Togni de Lima e Silva; Campos, Rosana Teresa Onocko

    2014-06-01

    A literature review was conducted aiming to understand the interface between the Intellectual Disability and Mental Health fields and to contribute to mitigating the path of institutionalizing individuals with intellectual deficiencies. The so-called dual diagnosis phenomenon remains underestimated in Brazil but is the object of research and specific public policy internationally. This phenomenon alerts us to the prevalence of mental health problems in those with intellectual disabilities, limiting their social inclusion. The findings reinforce the importance of this theme and indicate possible diagnostic invisibility of the development of mental illness in those with intellectual disabilities in Brazil, which may contribute to sustaining psychiatric institutionalization of this population. 

  11. Job enrichment: creating meaningful career development opportunities for nurses.

    PubMed

    Duffield, Christine; Baldwin, Richard; Roche, Michael; Wise, Sarah

    2014-09-01

    This paper presents an evaluation of a career development policy in South Australia which increased the number of senior staff nurse positions and provided senior registered nurses with time away from clinical duties to undertake agreed projects. We use Kanter's model of structural power and commitment theory to understand the dimensions of this policy. Development strategies for experienced staff who wish to remain at the bedside are needed, especially in smaller health services with limited opportunities for horizontal or vertical mobility. Face-to-face semistructured interviews were conducted with 54 senior staff nurses who participated in the career structure arrangements. The policy enhanced the structure of opportunity in three ways: by increasing the number of senior staff nurse positions, the ladder steps were improved; undertaking strategic projects developed new skills; and the job enrichment approach facilitated time out from the immediate pressures of ward work and challenged nurses in a different way. Through job enrichment, South Australia has found a novel way of providing meaningful career development opportunities for experienced nurses. Methods of job enrichment need to be considered as part of career development policy, especially where movement between clinical facilities is limited and staff wish to remain at the bedside. © 2013 John Wiley & Sons Ltd.

  12. Exploration of the Climate Change Frontier in Polar Regions at the Land Ice-Ocean Boundary.

    NASA Astrophysics Data System (ADS)

    Rignot, E. J.

    2014-12-01

    Ice sheets are the largest contributors to sea level rise at present, and responsible for the largest uncertainty in sea level projections. Ice sheets raised sea level 5 m per century 13.5 kyr ago during one period of rapid change. Leading regions for future rapid changes include the marine-based, retrograde bed parts of Greenland (north center and east), West Antarctica (Amundsen Sea), and East Antarctica (Filchner basin and Wilkes Land). Fast changes require an increase in ice melt from a warmer ocean and an increase in iceberg calving. Our understanding of both processes remains limited due to a lack of basic observations. Understanding ocean forcing requires observations on the continental shelf, along bays and glacial fjords and at ice-ocean boundaries, beneath kilometers of ice (Antarctica) or at near-vertical calving cliffs (Greenland), of ocean temperature and sea floor bathymetry. Where such observations exist, the sea floor is much deeper than anticipated because of the carving of deep channels by multiple glacier advances. Warm subsurface waters penetrate throughout the Amundsen Sea Embayment of West Antarctica, the southeast and probably the entire west coasts of Greenland. In Greenland, discharge of subglacial water from surface runoff at the glacier grounding line increases ice melting by the ocean even if the ocean temperature remains the same. Near ice-ocean boundaries, satellite observations are challenged, airborne observations and field surveys are limited, so advanced robotic techniques for cold, deep, remote environments are ultimately required in combination with advanced numerical modeling techniques. Until such technological advances take place and advanced networks are put in place, it is critical to conduct boat surveys, install moorings, and conduct extensive airborne campaigns (for instance, gravity-derived bathymetry and air-dropped CTDs), some of which is already taking place. In the meantime, projections of ice sheet evolution in a warmer climate will remain highly conservative and perhaps misleading. Furthermore, as glaciers destabilize, iceberg calving will take over. Calving depends on the height of the calving cliff, the fracturing of ice near the ice front by strain rates or water; but the jury is also out about defining a universal calving law.

  13. Abundance and Distribution of Enteric Bacteria and Viruses in Coastal and Estuarine Sediments—a Review

    PubMed Central

    Hassard, Francis; Gwyther, Ceri L.; Farkas, Kata; Andrews, Anthony; Jones, Vera; Cox, Brian; Brett, Howard; Jones, Davey L.; McDonald, James E.; Malham, Shelagh K.

    2016-01-01

    The long term survival of fecal indicator organisms (FIOs) and human pathogenic microorganisms in sediments is important from a water quality, human health and ecological perspective. Typically, both bacteria and viruses strongly associate with particulate matter present in freshwater, estuarine and marine environments. This association tends to be stronger in finer textured sediments and is strongly influenced by the type and quantity of clay minerals and organic matter present. Binding to particle surfaces promotes the persistence of bacteria in the environment by offering physical and chemical protection from biotic and abiotic stresses. How bacterial and viral viability and pathogenicity is influenced by surface attachment requires further study. Typically, long-term association with surfaces including sediments induces bacteria to enter a viable-but-non-culturable (VBNC) state. Inherent methodological challenges of quantifying VBNC bacteria may lead to the frequent under-reporting of their abundance in sediments. The implications of this in a quantitative risk assessment context remain unclear. Similarly, sediments can harbor significant amounts of enteric viruses, however, the factors regulating their persistence remains poorly understood. Quantification of viruses in sediment remains problematic due to our poor ability to recover intact viral particles from sediment surfaces (typically <10%), our inability to distinguish between infective and damaged (non-infective) viral particles, aggregation of viral particles, and inhibition during qPCR. This suggests that the true viral titre in sediments may be being vastly underestimated. In turn, this is limiting our ability to understand the fate and transport of viruses in sediments. Model systems (e.g., human cell culture) are also lacking for some key viruses, preventing our ability to evaluate the infectivity of viruses recovered from sediments (e.g., norovirus). The release of particle-bound bacteria and viruses into the water column during sediment resuspension also represents a risk to water quality. In conclusion, our poor process level understanding of viral/bacterial-sediment interactions combined with methodological challenges is limiting the accurate source apportionment and quantitative microbial risk assessment for pathogenic organisms associated with sediments in aquatic environments. PMID:27847499

  14. Rabbits in the grave! Consequences of bioturbation on the Neandertal "burial" at Regourdou (Montignac-sur-Vézère, Dordogne).

    PubMed

    Pelletier, Maxime; Royer, Aurélien; Holliday, Trenton W; Discamps, Emmanuel; Madelaine, Stéphane; Maureille, Bruno

    2017-09-01

    The understanding of Neanderthal societies, both with regard to their funerary behaviors and their subsistence activities, is hotly debated. Old excavations and a lack of taphonomic context are often factors that limit our ability to address these questions. To better appreciate the exact nature of what is potentially the oldest burial in Western Europe, Regourdou (Montignac-sur-Vézère, Dordogne), and to better understand the taphonomy of this site excavated more than 50 years ago, we report in this contribution a study of the most abundant animals throughout its stratigraphy: the European rabbit (Oryctolagus cuniculus). In addition to questions surrounding the potential bioturbation of the site's stratigraphy, analysis of the Regourdou rabbits could provide new information on Neandertal subsistence behavior. The mortality profile, skeletal-part representation, breakage patterns, surface modification, and comparison with modern reference collections supports the hypothesis that the Regourdou rabbit remains were primarily accumulated due to natural (attritional) mortality. Radiocarbon dates performed directly on the rabbit remains give ages ranging within the second half of Marine Isotope Stage 3, notably younger than the regional Mousterian period. We posit that rabbits dug their burrows within Regourdou's sedimentological filling, likely inhabiting the site after it was filled. The impact of rabbit activity now brings into question both the reliability of the archaeostratigraphy of the site and the paleoenvironmental reconstructions previously proposed for it, and suggests rabbits may have played a role in the distribution of the Neandertal skeletal remains. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. App Usage Factor: A Simple Metric to Compare the Population Impact of Mobile Medical Apps.

    PubMed

    Lewis, Thomas Lorchan; Wyatt, Jeremy C

    2015-08-19

    One factor when assessing the quality of mobile apps is quantifying the impact of a given app on a population. There is currently no metric which can be used to compare the population impact of a mobile app across different health care disciplines. The objective of this study is to create a novel metric to characterize the impact of a mobile app on a population. We developed the simple novel metric, app usage factor (AUF), defined as the logarithm of the product of the number of active users of a mobile app with the median number of daily uses of the app. The behavior of this metric was modeled using simulated modeling in Python, a general-purpose programming language. Three simulations were conducted to explore the temporal and numerical stability of our metric and a simulated app ecosystem model using a simulated dataset of 20,000 apps. Simulations confirmed the metric was stable between predicted usage limits and remained stable at extremes of these limits. Analysis of a simulated dataset of 20,000 apps calculated an average value for the app usage factor of 4.90 (SD 0.78). A temporal simulation showed that the metric remained stable over time and suitable limits for its use were identified. A key component when assessing app risk and potential harm is understanding the potential population impact of each mobile app. Our metric has many potential uses for a wide range of stakeholders in the app ecosystem, including users, regulators, developers, and health care professionals. Furthermore, this metric forms part of the overall estimate of risk and potential for harm or benefit posed by a mobile medical app. We identify the merits and limitations of this metric, as well as potential avenues for future validation and research.

  16. A scoping review of crisis teams managing dementia in older people.

    PubMed

    Streater, Amy; Coleston-Shields, Donna Maria; Yates, Jennifer; Stanyon, Miriam; Orrell, Martin

    2017-01-01

    Research on crisis teams for older adults with dementia is limited. This scoping review aimed to 1) conduct a systematic literature review reporting on the effectiveness of crisis interventions for older people with dementia and 2) conduct a scoping survey with dementia crisis teams mapping services across England to understand operational procedures and identify what is currently occurring in practice. For the systematic literature review, included studies were graded using the Critical Appraisal Skills Programme checklist. For the scoping survey, Trusts across England were contacted and relevant services were identified that work with people with dementia experiencing a mental health crisis. The systematic literature review demonstrated limited evidence in support of crisis teams reducing the rate of hospital admissions, and despite the increase in number of studies, methodological limitations remain. For the scoping review, only half (51.8%) of the teams had a care pathway to manage crises and the primary need for referral was behavioral or psychological factors. Evidence in the literature for the effectiveness of crisis teams for older adults with dementia remains limited. Being mainly cohort designs can make it difficult to evaluate the effectiveness of the intervention. In practice, it appears that the pathway for care managing crisis for people with dementia varies widely across services in England. There was a wide range of names given to the provision of teams managing crisis for people with dementia, which may reflect the differences in the setup and procedures of the service. To provide evidence on crisis intervention teams, a comprehensive protocol is required to deliver a standardized care pathway and measurable intervention as part of a large-scale evaluation of effectiveness.

  17. A scoping review of crisis teams managing dementia in older people

    PubMed Central

    Streater, Amy; Coleston-Shields, Donna Maria; Yates, Jennifer; Stanyon, Miriam; Orrell, Martin

    2017-01-01

    Background Research on crisis teams for older adults with dementia is limited. This scoping review aimed to 1) conduct a systematic literature review reporting on the effectiveness of crisis interventions for older people with dementia and 2) conduct a scoping survey with dementia crisis teams mapping services across England to understand operational procedures and identify what is currently occurring in practice. Methods For the systematic literature review, included studies were graded using the Critical Appraisal Skills Programme checklist. For the scoping survey, Trusts across England were contacted and relevant services were identified that work with people with dementia experiencing a mental health crisis. Results The systematic literature review demonstrated limited evidence in support of crisis teams reducing the rate of hospital admissions, and despite the increase in number of studies, methodological limitations remain. For the scoping review, only half (51.8%) of the teams had a care pathway to manage crises and the primary need for referral was behavioral or psychological factors. Conclusion Evidence in the literature for the effectiveness of crisis teams for older adults with dementia remains limited. Being mainly cohort designs can make it difficult to evaluate the effectiveness of the intervention. In practice, it appears that the pathway for care managing crisis for people with dementia varies widely across services in England. There was a wide range of names given to the provision of teams managing crisis for people with dementia, which may reflect the differences in the setup and procedures of the service. To provide evidence on crisis intervention teams, a comprehensive protocol is required to deliver a standardized care pathway and measurable intervention as part of a large-scale evaluation of effectiveness. PMID:29042760

  18. Learning and Teaching Climate Science: The Perils of Consensus Knowledge Using Agnotology

    NASA Astrophysics Data System (ADS)

    Legates, David R.; Soon, Willie; Briggs, William M.

    2013-08-01

    Agnotology has been defined in a variety of ways including "the study of ignorance and its cultural production" and "the study of how and why ignorance or misunderstanding exists." More recently, however, it has been posited that agnotology should be used in the teaching of climate change science. But rather than use agnotology to enhance an understanding of the complicated nature of the complex Earth's climate, the particular aim is to dispel alternative viewpoints to the so-called consensus science. One-sided presentations of controversial topics have little place in the classroom as they serve only to stifle debate and do not further knowledge and enhance critical thinking. Students must understand not just what is known and why it is known to be true but also what remains unknown and where the limitations on scientific understanding lie. Fact recitation coupled with demonizing any position or person who disagrees with a singularly-derived conclusion has no place in education. Instead, all sides must be covered in highly debatable and important topics such as climate change, because authoritarian science never will have all the answers to such complex problems.

  19. Influencing relatives to respect donor autonomy: Should we nudge families to consent to organ donation?

    PubMed

    Sharif, Adnan; Moorlock, Greg

    2018-03-01

    Refusing consent to organ donation remains unacceptably high, and improving consent rates from family or next-of-kin is an important step to procuring more organs for solid organ transplantation in countries where this approval is sought. We have thus far failed to translate fully our limited understanding of why families refuse permission into successful strategies targeting consent in the setting of deceased organ donation, primarily because our interventions fail to target underlying cognitive obstacles. Novel interventions to overcome these hurdles, incorporating an understanding of cognitive psychology and behavioral change therapy, may be beneficial. One potential intervention is to use the concept of nudge theory, where decision-making is influenced by encouraging positive reinforcement and indirect suggestion. Purposefully nudging families to given consent for organ donation by understanding, and then overcoming, their inherent cognitive biases is novel but also controversial. This article explores the roles of relatives in decisions about organ donation, how nudge theory translates to organ donation and discusses the arguments for and against its application. © 2018 John Wiley & Sons Ltd.

  20. Eccentric action of muscles: physiology, injury, and adaptation.

    PubMed

    Stauber, W T

    1989-01-01

    Eccentric muscle action deserves special consideration from the standpoint of physiology, adaptation, and training. The function of muscles as shock absorbers or springs seems to be quite different from other actions described in classical descriptions of muscle biology. This uniqueness certainly requires a more careful understanding of muscle as a unit consisting of myofibers and fascia which may work together or in opposition in response to chronic or acute stimuli. In addition, the stretch-shortening cycle is a special case of its own. However, from the standpoint of maximum human performance, there remain tremendous gaps in our understanding of the role of eccentric muscle action and its use in athletic training. How much is good? Does microfibrosis represent a problem of overtraining and eventually limit performance, or is it advantageous for success? Is the body-builder really developing muscle or connective tissue separating muscles? How does eccentric muscle action sometimes produce pain but not always? It would appear that much work is needed before a complete understanding of eccentric muscle action is obtained. This brief review has been designed to encourage research, argument, and discussion.

  1. Genetic determinants in head and neck squamous cell carcinoma and their influence on global personalized medicine

    PubMed Central

    Michmerhuizen, Nicole L.; Birkeland, Andrew C.; Bradford, Carol R.; Brenner, J. Chad

    2016-01-01

    While sequencing studies have provided an improved understanding of the genetic landscape of head and neck squamous cell carcinomas (HNSCC), there remains a significant lack of genetic data derived from non-Caucasian cohorts. Additionally, there is wide variation in HNSCC incidence and mortality worldwide both between and within various geographic regions. These epidemiologic differences are in part accounted for by varying exposure to environmental risk factors such as tobacco, alcohol, high risk human papilloma viruses and betel quid. However, inherent genetic factors may also play an important role in this variability. As limited sequencing data is available for many populations, the involvement of unique genetic factors in HNSCC pathogenesis from epidemiologically diverse groups is unknown. Here, we review current knowledge about the epidemiologic, environmental, and genetic variation in HNSCC cohorts globally and discuss future studies necessary to further our understanding of these differences. Long-term, a more complete understanding of the genetic drivers found in diverse HNSCC cohorts may help the development of personalized medicine protocols for patients with rare or complex genetic events. PMID:27551333

  2. Balancing water resources development and environmental sustainability in Africa: a review of recent research findings and applications.

    PubMed

    McClain, Michael E

    2013-09-01

    Sustainable development in Africa is dependent on increasing use of the continent's water resources without significantly degrading ecosystem services that are also fundamental to human wellbeing. This is particularly challenging in Africa because of high spatial and temporal variability in the availability of water resources and limited amounts of total water availability across expansive semi-arid portions of the continent. The challenge is compounded by ambitious targets for increased water use and a rush of international funding to finance development activities. Balancing development with environmental sustainability requires (i) understanding the boundary conditions imposed by the continent's climate and hydrology today and into the future, (ii) estimating the magnitude and spatial distribution of water use needed to meet development goals, and (iii) understanding the environmental water requirements of affected ecosystems, their current status and potential consequences of increased water use. This article reviews recent advancements in each of these topics and highlights innovative approaches and tools available to support sustainable development. While much remains to be learned, scientific understanding and technology should not be viewed as impediments to sustainable development on the continent.

  3. Disability transitions and health expectancies among adults 45 years and older in Malawi: a cohort-based model.

    PubMed

    Payne, Collin F; Mkandawire, James; Kohler, Hans-Peter

    2013-01-01

    Falling fertility and increasing life expectancy contribute to a growing elderly population in sub-Saharan Africa (SSA); by 2060, persons aged 45 y and older are projected to be 25% of SSA's population, up from 10% in 2010. Aging in SSA is associated with unique challenges because of poverty and inadequate social supports. However, despite its importance for understanding the consequences of population aging, the evidence about the prevalence of disabilities and functional limitations due to poor physical health among older adults in SSA continues to be very limited. Participants came from 2006, 2008, and 2010 waves of the Malawi Longitudinal Survey of Families and Health, a study of the rural population in Malawi. We investigate how poor physical health results in functional limitations that limit the day-to-day activities of individuals in domains relevant to this subsistence-agriculture context. These disabilities were parameterized based on questions from the SF-12 questionnaire about limitations in daily living activities. We estimated age-specific patterns of functional limitations and the transitions over time between different disability states using a discrete-time hazard model. The estimated transition rates were then used to calculate the first (to our knowledge) microdata-based health expectancies calculated for SSA. The risks of experiencing functional limitations due to poor physical health are high in this population, and the onset of disabilities happens early in life. Our analyses show that 45-y-old women can expect to spend 58% (95% CI, 55%-64%) of their remaining 28 y of life (95% CI, 25.7-33.5) with functional limitations; 45-y-old men can expect to live 41% (95% CI, 35%-46%) of their remaining 25.4 y (95% CI, 23.3-28.8) with such limitations. Disabilities related to functional limitations are shown to have a substantial negative effect on individuals' labor activities, and are negatively related to subjective well-being. Individuals in this population experience a lengthy struggle with disabling conditions in adulthood, with high probabilities of remitting and relapsing between states of functional limitation. Given the strong association of disabilities with work efforts and subjective well-being, this research suggests that current national health policies and international donor-funded health programs in SSA inadequately target the physical health of mature and older adults.

  4. Justice foundations for the Comprehensive Law Movement.

    PubMed

    Dewhurst, Dale

    2010-01-01

    Authors examining the developing dispute resolution alternatives to the adversarial system have identified nine converging "vectors" or alternatives in what has been termed the Comprehensive Law Movement. These authors have sought to understand how the developing vectors can remain separate and vibrant movements while sharing common ground. Some analyze these developments as being within law and legal practice, others see them as alternative approaches to law, and still others take a combined approach. It will be impossible to understand how these vectors have meaningful differences from law and legal practice if the search is limited to looking within law and legal practice. It will be impossible to understand how these vectors have meaningful commonalities with law and legal practice if the search is limited to looking external to law and legal practice. Instead of comparing the vectors with the adversarial system, higher order criteria are required. What is needed is a comprehensive and internally consistent super-system of norms; one that can be used to evaluate the adversarial system and the evolving vectors on an equal footing. An Aristotelian natural law virtue theory of justice can: (a) provide a functional guiding definition of justice; (b) serve as a comprehensive and internally consistent super-system of norms; and (c) provide the theoretical and evaluative foundation required to clarify the relationships among the adversarial system and the developing vectors. Finally, it will become clear why the Comprehensive Law Movement might be more appropriately conceptualized as the Comprehensive Justice Movement. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Regulation of µ-Opioid Receptors: Desensitization, Phosphorylation, Internalization, and Tolerance

    PubMed Central

    Williams, John T.; Ingram, Susan L.; Henderson, Graeme; Chavkin, Charles; von Zastrow, Mark; Schulz, Stefan; Koch, Thomas; Evans, Christopher J.

    2013-01-01

    Morphine and related µ-opioid receptor (MOR) agonists remain among the most effective drugs known for acute relief of severe pain. A major problem in treating painful conditions is that tolerance limits the long-term utility of opioid agonists. Considerable effort has been expended on developing an understanding of the molecular and cellular processes that underlie acute MOR signaling, short-term receptor regulation, and the progression of events that lead to tolerance for different MOR agonists. Although great progress has been made in the past decade, many points of contention and controversy cloud the realization of this progress. This review attempts to clarify some confusion by clearly defining terms, such as desensitization and tolerance, and addressing optimal pharmacological analyses for discerning relative importance of these cellular mechanisms. Cellular and molecular mechanisms regulating MOR function by phosphorylation relative to receptor desensitization and endocytosis are comprehensively reviewed, with an emphasis on agonist-biased regulation and areas where knowledge is lacking or controversial. The implications of these mechanisms for understanding the substantial contribution of MOR signaling to opioid tolerance are then considered in detail. While some functional MOR regulatory mechanisms contributing to tolerance are clearly understood, there are large gaps in understanding the molecular processes responsible for loss of MOR function after chronic exposure to opioids. Further elucidation of the cellular mechanisms that are regulated by opioids will be necessary for the successful development of MOR-based approaches to new pain therapeutics that limit the development of tolerance. PMID:23321159

  6. Positive feedback in the transition from sexual reproduction to parthenogenesis.

    PubMed

    Schwander, Tanja; Vuilleumier, Séverine; Dubman, Janie; Crespi, Bernard J

    2010-05-07

    Understanding how new phenotypes evolve is challenging because intermediate stages in transitions from ancestral to derived phenotypes often remain elusive. Here we describe and evaluate a new mechanism facilitating the transition from sexual reproduction to parthenogenesis. In many sexually reproducing species, a small proportion of unfertilized eggs can hatch spontaneously ('tychoparthenogenesis') and develop into females. Using an analytical model, we show that if females are mate-limited, tychoparthenogenesis can result in the loss of males through a positive feedback mechanism whereby tychoparthenogenesis generates female-biased sex ratios and increasing mate limitation. As a result, the strength of selection for tychoparthenogenesis increases in concert with the proportion of tychoparthenogenetic offspring in the sexual population. We then tested the hypothesis that mate limitation selects for tychoparthenogenesis and generates female-biased sex ratios, using data from natural populations of sexually reproducing Timema stick insects. Across 41 populations, both the tychoparthenogenesis rates and the proportions of females increased exponentially as the density of individuals decreased, consistent with the idea that low densities of individuals result in mate limitation and selection for reproductive insurance through tychoparthenogenesis. Our model and data from Timema populations provide evidence for a simple mechanism through which parthenogenesis can evolve rapidly in a sexual population.

  7. Professional diversity and the productivity of cities.

    PubMed

    Bettencourt, Luís M A; Samaniego, Horacio; Youn, Hyejin

    2014-06-23

    Attempts to understand the relationship between diversity, productivity and scale have remained limited due to the scheme-dependent nature of the taxonomies describing complex systems. We analyze the diversity of US metropolitan areas in terms of profession diversity and employment to show how this frequency distribution takes a universal scale-invariant form, common to all cities, in the limit of infinite resolution of occupational taxonomies. We show that this limit is obtained under general conditions that follow from the analysis of the variation of the occupational frequency across taxonomies at different resolutions in a way analogous to finite-size scaling in statistical physical systems. We propose a theoretical framework that derives the form and parameters of the limiting distribution of professions based on the appearance, in urban social networks, of new occupations as the result of specialization and coordination of labor. By deriving classification scheme-independent measures of functional diversity and modeling cities as social networks embedded in infrastructural space, these results show how standard economic arguments of division and coordination of labor can be articulated in detail in cities and provide a microscopic basis for explaining increasing returns to population scale observed at the level of entire metropolitan areas.

  8. Measures of aging with disability in U.S. secondary data sets: Results of a scoping review.

    PubMed

    Putnam, Michelle; Molton, Ivan R; Truitt, Anjali R; Smith, Amanda E; Jensen, Mark P

    2016-01-01

    There remain significant knowledge gaps in our understanding of aging with long-term disability. It is possible that important advances in knowledge could be gained using existing secondary data sets. However, little is known regarding which of the data sets available to researchers contain the age-related measures needed for this purpose, specifically age of onset and/or duration of disability measures. To better understand the capacity to investigate aging with long-term disability (e.g. mobility limitation) and aging with long-term chronic conditions (e.g. spinal cord injury, multiple sclerosis) using extant data. Public use national and regional data sets were identified through existing reports, web-based searches, and expert nomination. The age- and disability-related variables, including age of onset and duration of disability, were tabulated for data sets meeting inclusion criteria. Analysis was descriptive. A total of N = 44 data sets were reviewed. Of these, 22 contained both age and disability variables. Within these 22 data sets, 9 contained an age of onset or duration of disability variable. Six of the nine data sets contained age of diagnosis for a single or set of health conditions. Onset of functional limitation is in two, and onset of self-reported and/or employment disability is in four, of the nine data sets respectively. There is some, but limited opportunity to investigate aging with long-term disability in extant U.S. public use secondary data sets. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Nitrogen and the Baltic Sea: managing nitrogen in relation to phosphorus.

    PubMed

    Elmgren, R; Larsson, U

    2001-10-26

    The Baltic is a large, brackish sea (4 x 10(5) km2) extending from 54N to approximately 66N, with a fourfold larger drainage area (population 8 x 10(7). Surface salinity (2 to 8 PSU) and hence biodiversity is low. In the last century, annual nutrient loads increased to 10(6) metric tons N and 5 x 10(4) ton P. Eutrophication is evident in the N-limited south, where cyanobacteria fix 2 to 4 x 10(5) ton N each summer, Secchi depths have been halved, and O2-deficient bottom areas have spread. Production remains low in the P-limited north. In nutrient-enriched coastal areas, phytoplankton blooms, toxic at times, and filamentous macroalgae reduce amenity values. Loads need to be reduced of both N, to reduce production, and P, to limit N-fixing cyanobacterial blooms. When large N-load reductions have been achieved locally, algal biomass has declined. So far, P loads have been reduced more than N loads. If this continues, a P-limited Baltic proper may result, very different from previous N-limited conditions. Reaching the management goal of halved anthropogenic N and P loads at minimum cost will require better understanding of biogeochemical nutrient cycles, economic evaluation of proposed measures, and improved stakeholder participation.

  10. Surface drift prediction in the Adriatic Sea using hyper-ensemble statistics on atmospheric, ocean and wave models: Uncertainties and probability distribution areas

    USGS Publications Warehouse

    Rixen, M.; Ferreira-Coelho, E.; Signell, R.

    2008-01-01

    Despite numerous and regular improvements in underlying models, surface drift prediction in the ocean remains a challenging task because of our yet limited understanding of all processes involved. Hence, deterministic approaches to the problem are often limited by empirical assumptions on underlying physics. Multi-model hyper-ensemble forecasts, which exploit the power of an optimal local combination of available information including ocean, atmospheric and wave models, may show superior forecasting skills when compared to individual models because they allow for local correction and/or bias removal. In this work, we explore in greater detail the potential and limitations of the hyper-ensemble method in the Adriatic Sea, using a comprehensive surface drifter database. The performance of the hyper-ensembles and the individual models are discussed by analyzing associated uncertainties and probability distribution maps. Results suggest that the stochastic method may reduce position errors significantly for 12 to 72??h forecasts and hence compete with pure deterministic approaches. ?? 2007 NATO Undersea Research Centre (NURC).

  11. Inflating bacterial cells by increased protein synthesis

    PubMed Central

    Basan, Markus; Zhu, Manlu; Dai, Xiongfeng; Warren, Mya; Sévin, Daniel; Wang, Yi-Ping; Hwa, Terence

    2015-01-01

    Understanding how the homeostasis of cellular size and composition is accomplished by different organisms is an outstanding challenge in biology. For exponentially growing Escherichia coli cells, it is long known that the size of cells exhibits a strong positive relation with their growth rates in different nutrient conditions. Here, we characterized cell sizes in a set of orthogonal growth limitations. We report that cell size and mass exhibit positive or negative dependences with growth rate depending on the growth limitation applied. In particular, synthesizing large amounts of “useless” proteins led to an inversion of the canonical, positive relation, with slow growing cells enlarged 7- to 8-fold compared to cells growing at similar rates under nutrient limitation. Strikingly, this increase in cell size was accompanied by a 3- to 4-fold increase in cellular DNA content at slow growth, reaching up to an amount equivalent to ∼8 chromosomes per cell. Despite drastic changes in cell mass and macromolecular composition, cellular dry mass density remained constant. Our findings reveal an important role of protein synthesis in cell division control. PMID:26519362

  12. An elegant route to overcome fundamentally-limited light extraction in AlGaN deep-ultraviolet light-emitting diodes: Preferential outcoupling of strong in-plane emission

    PubMed Central

    Lee, Jong Won; Kim, Dong Yeong; Park, Jun Hyuk; Schubert, E. Fred; Kim, Jungsub; Lee, Jinsub; Kim, Yong-Il; Park, Youngsoo; Kim, Jong Kyu

    2016-01-01

    While there is an urgent need for semiconductor-based efficient deep ultraviolet (DUV) sources, the efficiency of AlGaN DUV light-emitting diodes (LEDs) remains very low because the extraction of DUV photons is significantly limited by intrinsic material properties of AlGaN. Here, we present an elegant approach based on a DUV LED having multiple mesa stripes whose inclined sidewalls are covered by a MgF2/Al omni-directional mirror to take advantage of the strongly anisotropic transverse-magnetic polarized emission pattern of AlGaN quantum wells. The sidewall-emission-enhanced DUV LED breaks through the fundamental limitations caused by the intrinsic properties of AlGaN, thus shows a remarkable improvement in light extraction as well as operating voltage. Furthermore, an analytic model is developed to understand and precisely estimate the extraction of DUV photons from AlGaN DUV LEDs, and hence to provide promising routes for maximizing the power conversion efficiency. PMID:26935402

  13. An elegant route to overcome fundamentally-limited light extraction in AlGaN deep-ultraviolet light-emitting diodes: Preferential outcoupling of strong in-plane emission

    NASA Astrophysics Data System (ADS)

    Lee, Jong Won; Kim, Dong Yeong; Park, Jun Hyuk; Schubert, E. Fred; Kim, Jungsub; Lee, Jinsub; Kim, Yong-Il; Park, Youngsoo; Kim, Jong Kyu

    2016-03-01

    While there is an urgent need for semiconductor-based efficient deep ultraviolet (DUV) sources, the efficiency of AlGaN DUV light-emitting diodes (LEDs) remains very low because the extraction of DUV photons is significantly limited by intrinsic material properties of AlGaN. Here, we present an elegant approach based on a DUV LED having multiple mesa stripes whose inclined sidewalls are covered by a MgF2/Al omni-directional mirror to take advantage of the strongly anisotropic transverse-magnetic polarized emission pattern of AlGaN quantum wells. The sidewall-emission-enhanced DUV LED breaks through the fundamental limitations caused by the intrinsic properties of AlGaN, thus shows a remarkable improvement in light extraction as well as operating voltage. Furthermore, an analytic model is developed to understand and precisely estimate the extraction of DUV photons from AlGaN DUV LEDs, and hence to provide promising routes for maximizing the power conversion efficiency.

  14. The importance of Evolutionary Medicine in developing countries: A case for Pakistan's medical schools.

    PubMed

    Enam, Syed Faaiz; Hashmi, Shumaila

    2018-01-01

    Evolutionary Medicine (EM) is a fundamental science exploring why our bodies are plagued with disease and hindered by limitations. EM views the body as an assortment of benefits, mistakes, and compromises molded over millennia. It highlights the role of evolution in numerous diseases encountered in community and family medicine clinics of developing countries. It enables us to ask informed questions and develop novel responses to global health problems. An understanding of the field is thus crucial for budding doctors, but its study is currently limited to a handful of medical schools in high-income countries. For the developing world, Pakistan's medical schools may be excellent starting posts as the country is beset with communicable and non-communicable diseases that are shaped by evolution. Remarkably, Pakistani medical students are open to studying and incorporating EM into their training. Understanding the principles of EM could empower them to tackle growing health problems in the country. Additionally, some difficulties that western medical schools face in integrating EM into their curriculum may not be a hindrance in Pakistan. We propose solutions for the remaining challenges, including obstinate religious sentiments. Herein, we make the case that incorporating EM is particularly important in developing countries such as Pakistan and that it is achievable in its medical student body.

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

    PubMed

    Fletcher-Lartey, Stephanie M; Caprarelli, Graziella

    2016-04-01

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

  16. Varying selection differential throughout the climatic range of Norway spruce in Central Europe.

    PubMed

    Kapeller, Stefan; Dieckmann, Ulf; Schueler, Silvio

    2017-01-01

    Predicting species distribution changes in global warming requires an understanding of how climatic constraints shape the genetic variation of adaptive traits and force local adaptations. To understand the genetic capacity of Norway spruce populations in Central Europe, we analyzed the variation in tree heights at the juvenile stage in common garden experiments established from the species' warm-dry to cold-moist distribution limits. We report the following findings: First, 47% of the total tree height variation at trial sites is attributable to the tree populations irrespective of site climate. Second, tree height variation within populations is higher at cold-moist trial sites than at warm-dry sites and higher within populations originating from cold-moist habitats than from warm-dry habitats. Third, for tree ages of 7-15 years, the variation within populations increases at cold-moist trial sites, whereas it remains constant at warm-dry sites. Fourth, tree height distributions are right-skewed at cold-moist trial sites, whereas they are nonskewed, but platykurtic at warm-dry sites. Our results suggest that in cold environments, climatic conditions impose stronger selection and probably restrict the distribution of spruce, whereas at the warm distribution limit, the species' realized niche might rather be controlled by external drivers, for example, forest insects.

  17. Impact of degree truncation on the spread of a contagious process on networks.

    PubMed

    Harling, Guy; Onnela, Jukka-Pekka

    2018-03-01

    Understanding how person-to-person contagious processes spread through a population requires accurate information on connections between population members. However, such connectivity data, when collected via interview, is often incomplete due to partial recall, respondent fatigue or study design, e.g., fixed choice designs (FCD) truncate out-degree by limiting the number of contacts each respondent can report. Past research has shown how FCD truncation affects network properties, but its implications for predicted speed and size of spreading processes remain largely unexplored. To study the impact of degree truncation on predictions of spreading process outcomes, we generated collections of synthetic networks containing specific properties (degree distribution, degree-assortativity, clustering), and also used empirical social network data from 75 villages in Karnataka, India. We simulated FCD using various truncation thresholds and ran a susceptible-infectious-recovered (SIR) process on each network. We found that spreading processes propagated on truncated networks resulted in slower and smaller epidemics, with a sudden decrease in prediction accuracy at a level of truncation that varied by network type. Our results have implications beyond FCD to truncation due to any limited sampling from a larger network. We conclude that knowledge of network structure is important for understanding the accuracy of predictions of process spread on degree truncated networks.

  18. Acute rejection in vascularized composite allotransplantation.

    PubMed

    Fischer, Sebastian; Lian, Christine G; Kueckelhaus, Maximilian; Strom, Terry B; Edelman, Elazer R; Clark, Rachel A; Murphy, George F; Chandraker, Anil K; Riella, Leonardo V; Tullius, Stefan G; Pomahac, Bohdan

    2014-12-01

    Acute rejection is the most common complication after vascularized composite allotransplantation (VCA). This review provides a state-of-the-art analysis of prevention, diagnosis and treatment of acute rejection episodes and highlights recent findings with the potential to improve patient care and enhance understanding of the underlying biologic processes. Recent reports suggest that maintenance immunosuppression dose reduction and steroid withdrawal are realistic goals in VCA, despite the known high immunogenicity of the skin component. It appears that utilization of sentinel flaps, in-depth histological analyses and application of novel biomarkers have facilitated early diagnosis and characterization of acute rejection episodes, leading to timely institution of appropriate therapy. The successful management of the first highly sensitized face transplant recipient suggests the possibility of carefully considering these high-risk VCA candidates for transplantation. Acute rejection is higher in VCA than in any other organ in the field of transplantation, although most episodes are controlled by high-dose steroids and optimization of maintenance immunosuppression. Because of limitations in patient number and the duration of follow-up, the long-term safety and effectiveness of VCA remain unclear. Moreover, the tests currently used to diagnose acute rejection are of limited value. Better diagnostic tools and a better understanding of the immunologic events during acute rejection are therefore needed to improve diagnosis, treatment and outcomes of this life-changing restorative surgery.

  19. The importance of Evolutionary Medicine in developing countries

    PubMed Central

    Hashmi, Shumaila

    2018-01-01

    Abstract Evolutionary Medicine (EM) is a fundamental science exploring why our bodies are plagued with disease and hindered by limitations. EM views the body as an assortment of benefits, mistakes, and compromises molded over millennia. It highlights the role of evolution in numerous diseases encountered in community and family medicine clinics of developing countries. It enables us to ask informed questions and develop novel responses to global health problems. An understanding of the field is thus crucial for budding doctors, but its study is currently limited to a handful of medical schools in high-income countries. For the developing world, Pakistan's medical schools may be excellent starting posts as the country is beset with communicable and non-communicable diseases that are shaped by evolution. Remarkably, Pakistani medical students are open to studying and incorporating EM into their training. Understanding the principles of EM could empower them to tackle growing health problems in the country. Additionally, some difficulties that western medical schools face in integrating EM into their curriculum may not be a hindrance in Pakistan. We propose solutions for the remaining challenges, including obstinate religious sentiments. Herein, we make the case that incorporating EM is particularly important in developing countries such as Pakistan and that it is achievable in its medical student body. PMID:29492264

  20. The state of the art of predicting noise-induced sleep disturbance in field settings.

    PubMed

    Fidell, Sanford; Tabachnick, Barbara; Pearsons, Karl S

    2010-01-01

    Several relationships between intruding noises (largely aircraft) and sleep disturbance have been inferred from the findings of a handful of field studies. Comparisons of sleep disturbance rates predicted by the various relationships are complicated by inconsistent data collection methods and definitions of predictor variables and predicted quantities. None of the relationships is grounded in theory-based understanding, and some depend on questionable statistical assumptions and analysis procedures. The credibility, generalizability, and utility of sleep disturbance predictions are also limited by small and nonrepresentative samples of test participants, and by restricted (airport-specific and relatively short duration) circumstances of exposure. Although expedient relationships may be the best available, their predictions are of only limited utility for policy analysis and regulatory purposes, because they account for very little variance in the association between environmental noise and sleep disturbance, have characteristically shallow slopes, have not been well validated in field settings, are highly context-dependent, and do not squarely address the roles and relative importance of nonacoustic factors in sleep disturbance. Such relationships offer the appearance more than the substance of precision and objectivity. Truly useful, population-level prediction and genuine understanding of noise-induced sleep disturbance will remain beyond reach for the foreseeable future, until the findings of field studies of broader scope and more sophisticated design become available.

  1. Students' Images and Their Understanding of Definitions of the Limit of a Sequence

    ERIC Educational Resources Information Center

    Roh, Kyeong Hah

    2008-01-01

    There are many studies on the role of images in understanding the concept of limit. However, relatively few studies have been conducted on how students' understanding of the rigorous definition of limit is influenced by the images of limit that the students have constructed through their previous learning. This study explored how calculus…

  2. Experiments to Determine Whether Recursive Partitioning (CART) or an Artificial Neural Network Overcomes Theoretical Limitations of Cox Proportional Hazards Regression

    NASA Technical Reports Server (NTRS)

    Kattan, Michael W.; Hess, Kenneth R.; Kattan, Michael W.

    1998-01-01

    New computationally intensive tools for medical survival analyses include recursive partitioning (also called CART) and artificial neural networks. A challenge that remains is to better understand the behavior of these techniques in effort to know when they will be effective tools. Theoretically they may overcome limitations of the traditional multivariable survival technique, the Cox proportional hazards regression model. Experiments were designed to test whether the new tools would, in practice, overcome these limitations. Two datasets in which theory suggests CART and the neural network should outperform the Cox model were selected. The first was a published leukemia dataset manipulated to have a strong interaction that CART should detect. The second was a published cirrhosis dataset with pronounced nonlinear effects that a neural network should fit. Repeated sampling of 50 training and testing subsets was applied to each technique. The concordance index C was calculated as a measure of predictive accuracy by each technique on the testing dataset. In the interaction dataset, CART outperformed Cox (P less than 0.05) with a C improvement of 0.1 (95% Cl, 0.08 to 0.12). In the nonlinear dataset, the neural network outperformed the Cox model (P less than 0.05), but by a very slight amount (0.015). As predicted by theory, CART and the neural network were able to overcome limitations of the Cox model. Experiments like these are important to increase our understanding of when one of these new techniques will outperform the standard Cox model. Further research is necessary to predict which technique will do best a priori and to assess the magnitude of superiority.

  3. Vitamin C physiology: the known and the unknown and Goldilocks

    PubMed Central

    Padayatty, Sebastian J; Levine, Mark

    2016-01-01

    Vitamin C (Ascorbic Acid), the antiscorbutic vitamin, cannot be synthesized by humans and other primates, and has to be obtained from diet. Ascorbic acid is an electron donor and acts as a cofactor for fifteen mammalian enzymes. Two sodium-dependent transporters are specific for ascorbic acid, and its oxidation product dehydroascorbic acid is transported by glucose transporters. Ascorbic acid is differentially accumulated by most tissues and body fluids. Plasma and tissue vitamin C concentrations are dependent on amount consumed, bioavailability, renal excretion, and utilization. To be biologically meaningful or to be clinically relevant, in vitro and in vivo studies of vitamin C actions have to take into account physiologic concentrations of the vitamin. In this paper, we review vitamin C physiology; the many phenomena involving vitamin C where new knowledge has accrued or where understanding remains limited; raise questions about the vitamin that remain to be answered; and explore lines of investigations that are likely to be fruitful. PMID:26808119

  4. Alternative bacteriophage life cycles: the carrier state of Campylobacter jejuni

    PubMed Central

    Siringan, Patcharin; Connerton, Phillippa L.; Cummings, Nicola J.; Connerton, Ian F.

    2014-01-01

    Members of the genus Campylobacter are frequently responsible for human enteric disease, often through consumption of contaminated poultry products. Bacteriophages are viruses that have the potential to control pathogenic bacteria, but understanding their complex life cycles is key to their successful exploitation. Treatment of Campylobacter jejuni biofilms with bacteriophages led to the discovery that phages had established a relationship with their hosts typical of the carrier state life cycle (CSLC), where bacteria and bacteriophages remain associated in equilibrium. Significant phenotypic changes include improved aerotolerance under nutrient-limited conditions that would confer an advantage to survive in extra-intestinal environments, but a lack in motility eliminated their ability to colonize chickens. Under these circumstances, phages can remain associated with a compatible host and continue to produce free virions to prospect for new hosts. Moreover, we demonstrate that CSLC host bacteria can act as expendable vehicles for the delivery of bacteriophages to new host bacteria within pre-colonized chickens. The CSLC represents an important phase in the ecology of Campylobacter bacteriophage. PMID:24671947

  5. Alternative bacteriophage life cycles: the carrier state of Campylobacter jejuni.

    PubMed

    Siringan, Patcharin; Connerton, Phillippa L; Cummings, Nicola J; Connerton, Ian F

    2014-03-26

    Members of the genus Campylobacter are frequently responsible for human enteric disease, often through consumption of contaminated poultry products. Bacteriophages are viruses that have the potential to control pathogenic bacteria, but understanding their complex life cycles is key to their successful exploitation. Treatment of Campylobacter jejuni biofilms with bacteriophages led to the discovery that phages had established a relationship with their hosts typical of the carrier state life cycle (CSLC), where bacteria and bacteriophages remain associated in equilibrium. Significant phenotypic changes include improved aerotolerance under nutrient-limited conditions that would confer an advantage to survive in extra-intestinal environments, but a lack in motility eliminated their ability to colonize chickens. Under these circumstances, phages can remain associated with a compatible host and continue to produce free virions to prospect for new hosts. Moreover, we demonstrate that CSLC host bacteria can act as expendable vehicles for the delivery of bacteriophages to new host bacteria within pre-colonized chickens. The CSLC represents an important phase in the ecology of Campylobacter bacteriophage.

  6. Smart Point Cloud: Definition and Remaining Challenges

    NASA Astrophysics Data System (ADS)

    Poux, F.; Hallot, P.; Neuville, R.; Billen, R.

    2016-10-01

    Dealing with coloured point cloud acquired from terrestrial laser scanner, this paper identifies remaining challenges for a new data structure: the smart point cloud. This concept arises with the statement that massive and discretized spatial information from active remote sensing technology is often underused due to data mining limitations. The generalisation of point cloud data associated with the heterogeneity and temporality of such datasets is the main issue regarding structure, segmentation, classification, and interaction for an immediate understanding. We propose to use both point cloud properties and human knowledge through machine learning to rapidly extract pertinent information, using user-centered information (smart data) rather than raw data. A review of feature detection, machine learning frameworks and database systems indexed both for mining queries and data visualisation is studied. Based on existing approaches, we propose a new 3-block flexible framework around device expertise, analytic expertise and domain base reflexion. This contribution serves as the first step for the realisation of a comprehensive smart point cloud data structure.

  7. Electronystagmography and audio potentials in space flight

    NASA Technical Reports Server (NTRS)

    Thornton, William E.; Biggers, W. P.; Pool, Sam L.; Thomas, W. G.; Thagard, Norman E.

    1985-01-01

    Beginning with the fourth flight of the Space Transport System (STS-4), objective measurements of inner ear function were conducted in near-zero G conditions in earth orbit. The problem of space motion sickness (SMS) was approached much like any disequilibrium problem encountered clinically. However, objective testing techniques had built-in limitations superimposed by the strict parameters inherent in each mission. An attempt was made to objectively characterize SMS, and to first ascertain whether the objective measurements indicated that this disorder was of peripheral or central origin. Electronystagmography and auditory brain stem response recordings were the primary investigative tools. One of the authors (W.E.T.) was a mission specialist on board the orbiter Challenger on the eighth shuttle mission (STS-8) and had the opportunity to make direct and personal observations regarding SMS, an opportunity which has added immeasurably to our understanding of this disorder. Except for two abnormal ENG records, which remain to be explained, the remaining ENG records and all the ABR records made in the weightless environment of space were normal.

  8. Occupational Therapy for Adults With Cancer: Why It Matters

    PubMed Central

    Williams, Grant R.; Campbell, Claudine; Munoz, Lauro A.; Muss, Hyman B.

    2016-01-01

    Adults with cancer may be at risk for limitations in functional status and quality of life (QOL). Occupational therapy is a supportive service with the specific mission to help people functionally engage in life as safely and independently as possible with the primary goal of improving QOL. Unfortunately, for people with cancer, occupational therapy remains underused. The overall purpose of this review is to provide an understanding of what occupational therapy is and its relevance to patients with cancer, highlight the reasons to refer, and, last, provide general advice on how to access services. Implications for Practice: Adults with cancer are at risk for functional decline, which can lead to increased hospitalization, poor tolerance of cancer treatment, and increased health-care costs. Occupational therapy is specifically designed to evaluate and treat functional deficits, yet it remains underused in cancer care. This article describes what occupational therapy is, how to identify those who may need it, and how to access services. PMID:26865588

  9. Post-supereruption recovery at Toba Caldera

    PubMed Central

    Mucek, Adonara E.; Danišík, Martin; de Silva, Shanaka L.; Schmitt, Axel K.; Pratomo, Indyo; Coble, Matthew A.

    2017-01-01

    Large calderas, or supervolcanoes, are sites of the most catastrophic and hazardous events on Earth, yet the temporal details of post-supereruption activity, or resurgence, remain largely unknown, limiting our ability to understand how supervolcanoes work and address their hazards. Toba Caldera, Indonesia, caused the greatest volcanic catastrophe of the last 100 kyr, climactically erupting ∼74 ka. Since the supereruption, Toba has been in a state of resurgence but its magmatic and uplift history has remained unclear. Here we reveal that new 14C, zircon U–Th crystallization and (U–Th)/He ages show resurgence commenced at 69.7±4.5 ka and continued until at least ∼2.7 ka, progressing westward across the caldera, as reflected by post-caldera effusive lava eruptions and uplifted lake sediment. The major stratovolcano north of Toba, Sinabung, shows strong geochemical kinship with Toba, and zircons from recent eruption products suggest Toba's climactic magma reservoir extends beneath Sinabung and is being tapped during eruptions. PMID:28508876

  10. Wildlife in the cloud: a new approach for engaging stakeholders in wildlife management.

    PubMed

    Chapron, Guillaume

    2015-11-01

    Research in wildlife management increasingly relies on quantitative population models. However, a remaining challenge is to have end-users, who are often alienated by mathematics, benefiting from this research. I propose a new approach, 'wildlife in the cloud,' to enable active learning by practitioners from cloud-based ecological models whose complexity remains invisible to the user. I argue that this concept carries the potential to overcome limitations of desktop-based software and allows new understandings of human-wildlife systems. This concept is illustrated by presenting an online decision-support tool for moose management in areas with predators in Sweden. The tool takes the form of a user-friendly cloud-app through which users can compare the effects of alternative management decisions, and may feed into adjustment of their hunting strategy. I explain how the dynamic nature of cloud-apps opens the door to different ways of learning, informed by ecological models that can benefit both users and researchers.

  11. Long-term intensive electrically stimulated cycling by spinal cord-injured people: effect on muscle properties and their relation to power output.

    PubMed

    Duffell, Lynsey D; Donaldson, Nick de N; Perkins, Tim A; Rushton, David N; Hunt, Kenneth J; Kakebeeke, Tanja H; Newham, Di J

    2008-10-01

    Inactivity and muscular adaptations following spinal cord injury (SCI) result in secondary complications such as cardiovascular disease, obesity, and pressure sores. Functional electrically stimulated (FES) cycling can potentially reduce these complications, but previous studies have provided inconsistent results. We studied the effect of intensive long-term FES cycle training on muscle properties in 11 SCI subjects (mean +/- SEM: 41.8 +/- 2.3 years) who had trained for up to 1 hour/day, 5 days/week, for 1 year. Comparative measurements were made in 10 able-bodied (AB) subjects. Quadriceps maximal electrically stimulated torque increased fivefold (n = 5), but remained lower than in AB individuals. Relative force response at 1 HZ decreased, relaxation rate remained unchanged, and fatigue resistance improved significantly. Power output (PO) improved to a lesser extent than quadriceps torque and not to a greater extent than has been reported previously. We need to understand the factors that limit PO in order to maximize the benefits of FES cycling.

  12. Paleo-oncology: the role of ancient remains in the study of cancer.

    PubMed

    Halperin, Edward C

    2004-01-01

    Paleo-oncology is the study of carcinomas and sarcomas in ancient human populations and their hominid precursors. These populations are informative concerning the possible influences on cancer of morphologic and functional evolution, diet, lifestyle, and other environmental factors. The prevalence of cancer in ancient populations might have differed from that in modern humans, because of substantial differences in tobacco and alcohol use, diet, life expectancy, and the availability of treatment. The available physical data concerning cancer in antiquity includes evidence of its existence in animal fossils and ancient humans and their precursors. The difficulties of paleo-oncologic research include a limited soft tissue record. In evaluating cancer in ancient remains, one must also deal with the problem of pseudopathology: whether an observed tissue change is all antemortem pathologic lesion or a postmortem artifact. Future archeological discoveries and the application of improved diagnostic techniques may enable paleo-oncology to make further contributions to our understanding of cancer.

  13. Post-supereruption recovery at Toba Caldera.

    PubMed

    Mucek, Adonara E; Danišík, Martin; de Silva, Shanaka L; Schmitt, Axel K; Pratomo, Indyo; Coble, Matthew A

    2017-05-16

    Large calderas, or supervolcanoes, are sites of the most catastrophic and hazardous events on Earth, yet the temporal details of post-supereruption activity, or resurgence, remain largely unknown, limiting our ability to understand how supervolcanoes work and address their hazards. Toba Caldera, Indonesia, caused the greatest volcanic catastrophe of the last 100 kyr, climactically erupting ∼74 ka. Since the supereruption, Toba has been in a state of resurgence but its magmatic and uplift history has remained unclear. Here we reveal that new 14 C, zircon U-Th crystallization and (U-Th)/He ages show resurgence commenced at 69.7±4.5 ka and continued until at least ∼2.7 ka, progressing westward across the caldera, as reflected by post-caldera effusive lava eruptions and uplifted lake sediment. The major stratovolcano north of Toba, Sinabung, shows strong geochemical kinship with Toba, and zircons from recent eruption products suggest Toba's climactic magma reservoir extends beneath Sinabung and is being tapped during eruptions.

  14. Rheumatic Heart Disease in the Twenty-First Century.

    PubMed

    Woldu, Bethel; Bloomfield, Gerald S

    2016-10-01

    Rheumatic heart disease (RHD) is a chronic valvular disease resulting after severe or repetitive episodes of acute rheumatic fever (ARF), an autoimmune response to group A Streptococcus infection. RHD has been almost eliminated with improved social and health infrastructure in affluent countries while it remains a neglected disease with major cause of morbidity and mortality in many low- and middle-income countries, and resource-limited regions of high-income countries. Despite our evolving understanding of the pathogenesis of RHD, there have not been any significant advances to prevent or halt progression of disease in recent history. Long-term penicillin-based treatment and surgery remain the backbone of a RHD control program in the absence of an effective vaccine. The advent of echocardiographic screening algorithms has improved the accuracy of diagnosing RHD and has shed light on the enormous burden of disease. Encouragingly, this has led to a rekindled commitment from researchers in the most affected countries to advocate and take bold actions to end this disease of social inequality.

  15. Unified Synthesis Product (USP) Recommendations

    NASA Astrophysics Data System (ADS)

    Peterson, T. C.

    2009-05-01

    The USP identifies a number of areas in which inadequate information or understanding hampers our ability to estimate likely future climate change and its impacts. For example, our knowledge of changes in tornadoes, hail, and ice storms is quite limited, making it difficult to know if and how such events have changed as climate has warmed, and how they might change in the future. Research on ecological responses to climate change also is limited, as is our understanding of social responses. The Report identifies the five most important gaps in knowledge and offers some thoughts on how to address those gaps: 1. Expand our understanding of climate change impacts. There is a clear need to increase understanding of how ecosystems, social and economic systems, human health, and the built environment will be affected by climate change in the context of other stresses. This includes ecosystems as well as economic systems, human health, and the built environment. 2. Refine ability to project climate change at local scales. One of the main messages to emerge from the past decade of synthesis and assessments is that while climate change is a global issue, it has a great deal of regional variability. There is an indisputable need to improve understanding of climate system effects at these smaller scales, because these are often the scales of decision-making in society. 3. Expand capacity to provide decision makers and the public with relevant information on climate change and its impacts. The United States has tremendous potential to create more comprehensive measurement, archive, and data-access systems that could provide great benefit to society. 4. Improve understanding of and ability to identify thresholds likely to lead to abrupt changes in the climate system. Paleoclimatic data shows that climate can and has changed quite abruptly when certain thresholds are crossed. Similarly, there is evidence that ecological and human systems can undergo abrupt change when tipping points are reached. 5. Enhance understanding of how society can adapt to climate change in the context of multiple stresses. There is currently limited knowledge about the ability of communities, regions, and sectors to adapt to future climate change. It is essential to improve understanding of how the capacity to adapt to a changing climate might be exercised, and the vulnerabilities to climate change and other environmental stresses that might remain. Results from these efforts would inform future assessments that continue building our understanding of humanity's impacts on climate, and climate's impacts on us. Such assessments will continue to play a role in helping the U.S. respond to changing conditions. A vision for future climate change assessments includes both sustained extensive practitioner and stakeholder involvement, and periodic, targeted, scientifically rigorous reports similar to the CCSP Synthesis and Assessment Products.

  16. Can oxygen set thermal limits in an insect and drive gigantism?

    PubMed

    Verberk, Wilco C E P; Bilton, David T

    2011-01-01

    Thermal limits may arise through a mismatch between oxygen supply and demand in a range of animal taxa. Whilst this oxygen limitation hypothesis is supported by data from a range of marine fish and invertebrates, its generality remains contentious. In particular, it is unclear whether oxygen limitation determines thermal extremes in tracheated arthropods, where oxygen limitation may be unlikely due to the efficiency and plasticity of tracheal systems in supplying oxygen directly to metabolically active tissues. Although terrestrial taxa with open tracheal systems may not be prone to oxygen limitation, species may be affected during other life-history stages, particularly if these rely on diffusion into closed tracheal systems. Furthermore, a central role for oxygen limitation in insects is envisaged within a parallel line of research focussing on insect gigantism in the late Palaeozoic. Here we examine thermal maxima in the aquatic life stages of an insect at normoxia, hypoxia (14 kPa) and hyperoxia (36 kPa). We demonstrate that upper thermal limits do indeed respond to external oxygen supply in the aquatic life stages of the stonefly Dinocras cephalotes, suggesting that the critical thermal limits of such aquatic larvae are set by oxygen limitation. This could result from impeded oxygen delivery, or limited oxygen regulatory capacity, both of which have implications for our understanding of the limits to insect body size and how these are influenced by atmospheric oxygen levels. These findings extend the generality of the hypothesis of oxygen limitation of thermal tolerance, suggest that oxygen constraints on body size may be stronger in aquatic environments, and that oxygen toxicity may have actively selected for gigantism in the aquatic stages of Carboniferous arthropods.

  17. Can Oxygen Set Thermal Limits in an Insect and Drive Gigantism?

    PubMed Central

    Verberk, Wilco C. E. P.; Bilton, David T.

    2011-01-01

    Background Thermal limits may arise through a mismatch between oxygen supply and demand in a range of animal taxa. Whilst this oxygen limitation hypothesis is supported by data from a range of marine fish and invertebrates, its generality remains contentious. In particular, it is unclear whether oxygen limitation determines thermal extremes in tracheated arthropods, where oxygen limitation may be unlikely due to the efficiency and plasticity of tracheal systems in supplying oxygen directly to metabolically active tissues. Although terrestrial taxa with open tracheal systems may not be prone to oxygen limitation, species may be affected during other life-history stages, particularly if these rely on diffusion into closed tracheal systems. Furthermore, a central role for oxygen limitation in insects is envisaged within a parallel line of research focussing on insect gigantism in the late Palaeozoic. Methodology/Principal Findings Here we examine thermal maxima in the aquatic life stages of an insect at normoxia, hypoxia (14 kPa) and hyperoxia (36 kPa). We demonstrate that upper thermal limits do indeed respond to external oxygen supply in the aquatic life stages of the stonefly Dinocras cephalotes, suggesting that the critical thermal limits of such aquatic larvae are set by oxygen limitation. This could result from impeded oxygen delivery, or limited oxygen regulatory capacity, both of which have implications for our understanding of the limits to insect body size and how these are influenced by atmospheric oxygen levels. Conclusions/Significance These findings extend the generality of the hypothesis of oxygen limitation of thermal tolerance, suggest that oxygen constraints on body size may be stronger in aquatic environments, and that oxygen toxicity may have actively selected for gigantism in the aquatic stages of Carboniferous arthropods. PMID:21818347

  18. Understanding When and How Geoscientists Build Universal Skills and Competencies

    NASA Astrophysics Data System (ADS)

    Riggs, E. M.

    2015-12-01

    Geoscience educators and employers understand the pressing needs for the future workforce to be well-prepared in universal skills and competencies. At the undergraduate and graduate level today, most programs do a good job of this preparation, and employers are finding qualified applicants. However, with workforce needs in the geosciences projected to steadily outstrip supply in coming decades, and with many employers having to do substantial additional training on arrival for new hires, research informing curriculum design and skills development needs to be a priority. The projected retirement of seasoned professionals exacerbates this need and underscores the need to better understand the nature and structure of geoscience skills and competencies at the expert level. A workshop on Synthesizing Geoscience Education Research at the inaugural Earth Educator's Rendezvous began work on assembling a community-wide inventory of research progress. Groups began an assessment of our understanding of key skills in the geosciences as well as curricular approaches to maximize teaching effectiveness and recruitment and retention. It is clear that we have made basic progress on understanding spatial and temporal thinking, as well as systems thinking and geologic problem solving. However, most of this research is in early stages, limited to local populations, disciplines or contexts. Curricular innovations in the integration of quantitative, field-specific and computational techniques are also mostly local or limited in scope. Many programs also locally incorporate an explicit non-technical component, e.g. writing, business, and legal content or experience in team-based project-driven work. Despite much good practitioner wisdom, and a small but growing research base on effectiveness and best practices, we have much yet to learn about geoscience education, especially at the graduate and professional level. We remain far from a universal understanding of these skills and competencies, let alone how they should be most effectively taught to all geoscience students. We do understand universal geoscience skills and competencies better than ever before, but as a community we have a long way yet to go to construct and implement a broad strategy for meeting the geoscience workforce needs for the decades ahead.

  19. Secret science: tobacco industry research on smoking behaviour and cigarette toxicity.

    PubMed

    Hammond, David; Collishaw, Neil E; Callard, Cynthia

    2006-03-04

    A lack of scientific data remains the principal obstacle to regulating cigarette toxicity. In particular, there is an immediate need to improve our understanding of the interaction between smoking behaviour and product design, and its influence on cigarette deliveries. This article reviews internal tobacco industry documents on smoking behaviour research undertaken by Imperial Tobacco Limited (ITL) and British-American Tobacco (BAT). BAT documents indicate that smokers vary their puffing behaviour to regulate nicotine levels and compensate for low-yield cigarettes by smoking them more intensely. BAT research also shows that the tar and nicotine delivered to smokers is substantially greater than the machine-smoked yields reported to consumers and regulators. Internal documents describe a strategy to maximise this discrepancy through product design. In particular, BAT developed elastic cigarettes that produced low yields under standard testing protocols, whereas in consumers' hands they elicited more intensive smoking and provided higher concentrations of tar and nicotine to smokers. Documents also show that BAT pursued this product strategy despite the health risks to consumers and ethical concerns raised by senior scientists, and paired it with an equally successful marketing campaign that promoted these cigarettes as low-tar alternatives for health-concerned smokers. Overall, the documents seem to reveal a product strategy intended to exploit the limitations of the testing protocols and to intentionally conceal from consumers and regulators the potential toxicity of BAT products revealed by BAT's own research. Tobacco industry research underscores the serious limitations of the current cigarette testing protocols and the documents describe deceptive business practices that remain in place.

  20. Irradiation-Accelerated Corrosion of Reactor Core Materials. Final Report

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

    Jiao, Zhujie; Was, Gary; Bartels, David

    2015-04-02

    This project aims to understand how radiation accelerates corrosion of reactor core materials. The combination of high temperature, chemically aggressive coolants, a high radiation flux and mechanical stress poses a major challenge for the life extension of current light water reactors, as well as the success of most all GenIV concepts. Of these four drivers, the combination of radiation and corrosion places the most severe demands on materials, for which an understanding of the fundamental science is simply absent. Only a few experiments have been conducted to understand how corrosion occurs under irradiation, yet the limited data indicates that themore » effect is large; irradiation causes order of magnitude increases in corrosion rates. Without a firm understanding of the mechanisms by which radiation and corrosion interact in film formation, growth, breakdown and repair, the extension of the current LWR fleet beyond 60 years and the success of advanced nuclear energy systems are questionable. The proposed work will address the process of irradiation-accelerated corrosion that is important to all current and advanced reactor designs, but remains very poorly understood. An improved understanding of the role of irradiation in the corrosion process will provide the community with the tools to develop predictive models for in-reactor corrosion, and to address specific, important forms of corrosion such as irradiation assisted stress corrosion cracking.« less

  1. Opioid analgesics: does potency matter?

    PubMed

    Passik, Steven D; Webster, Lynn

    2014-01-01

    Prescription opioid analgesics with a wide range of potencies are currently used for the treatment of chronic pain. Yet understanding the clinical relevance and therapeutic consequences of opioid potency remains ill defined. Both patients and clinicians alike have misperceptions about opioid potency, expecting that less-potent opioids will be less effective or fearing that more-potent opioids are more dangerous or more likely to be abused. In this review, common myths about the potency of opioid analgesics will be discussed. Clinicians should understand that pharmacologic potency per se does not necessarily imply more effective analgesia or higher abuse liability. Published dose conversion tables may not accurately calculate the dose for effective and safe rotation from one opioid to another in patients receiving long-term opioid therapy because they are based on limited data that may not apply to chronic pain. Differences in pharmacologic potency are largely accounted for by the actual doses prescribed, according to individualized patient need. Factors for achieving effective analgesia and reducing the risks involved with opioid use include careful medication selection based on patient characteristics, appropriate dosing titration and opioid rotation practices, knowledge of product formulation characteristics (eg, extended release, immediate release, and tamper-resistant features), and an awareness of differences in opioid pharmacokinetics and metabolism. Clinicians should remain vigilant in monitoring patients on any opioid medication, regardless of classification along the opioid potency continuum.

  2. Inspiration for wing design: how forelimb specialization enables active flight in modern vertebrates.

    PubMed

    Chin, Diana D; Matloff, Laura Y; Stowers, Amanda Kay; Tucci, Emily R; Lentink, David

    2017-06-01

    Harnessing flight strategies refined by millions of years of evolution can help expedite the design of more efficient, manoeuvrable and robust flying robots. This review synthesizes recent advances and highlights remaining gaps in our understanding of how bird and bat wing adaptations enable effective flight. Included in this discussion is an evaluation of how current robotic analogues measure up to their biological sources of inspiration. Studies of vertebrate wings have revealed skeletal systems well suited for enduring the loads required during flight, but the mechanisms that drive coordinated motions between bones and connected integuments remain ill-described. Similarly, vertebrate flight muscles have adapted to sustain increased wing loading, but a lack of in vivo studies limits our understanding of specific muscular functions. Forelimb adaptations diverge at the integument level, but both bird feathers and bat membranes yield aerodynamic surfaces with a level of robustness unparalleled by engineered wings. These morphological adaptations enable a diverse range of kinematics tuned for different flight speeds and manoeuvres. By integrating vertebrate flight specializations-particularly those that enable greater robustness and adaptability-into the design and control of robotic wings, engineers can begin narrowing the wide margin that currently exists between flying robots and vertebrates. In turn, these robotic wings can help biologists create experiments that would be impossible in vivo . © 2017 The Author(s).

  3. A Contextual Work-Life Experiences Model to Understand Nurse Commitment and Turnover.

    PubMed

    Aluwihare-Samaranayake, Dilmi; Gellatly, Ian; Cummings, Greta; Ogilvie, Linda

    2018-05-17

    To present a discussion and model depicting most effecting work life experience contextual factors that influence commitment and turnover intentions for nurses in Sri Lanka. Increasing demand for nurses has made the retention of experienced, qualified nursing staff a priority for health care organizations and highlights the need to capture contextual work-life experiences that influence nurses' turnover decisions. Discussion paper. This discussion paper and model is based on our experiences and knowledge of Sri Lanka and represents an integration of classic turnover research and commitment theory and others published between 1958 - 2017, contextualized to reflect the reality faced by Sri Lanka nurses. The model presents a high-level view of intrinsic, extrinsic, personal and professional antecedents to nurse turnover where relevance can be used by researchers, policy makers, clinicians and educators to establish focused and limited scope models and examine comprehensive contexts. This model emphasizes the role that work-life experiences play to fortify (or weaken) nurses' motivation to remain committed to their organization, profession, family, and country. Understanding of contextual work-life influences on nurses' intent to stay should lead to evidence-based strategies that result in a higher number of nurses wanting to remain in the nursing profession and work in the health sector in Sri Lanka. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. Malaria in Uganda: challenges to control on the long road to elimination. I. Epidemiology and current control efforts

    PubMed Central

    Yeka, Adoke; Gasasira, Anne; Mpimbaza, Arthur; Achan, Jane; Nankabirwa, Joaniter; Nsobya, Sam; Staedke, Sarah G.; Donnelly, Martin J.; Wabwire-Mangen, Fred; Talisuna, Ambrose; Dorsey, Grant; Kamya, Moses R.; Rosenthal, Philip J.

    2011-01-01

    Malaria remains one of the leading health problems of the developing world, and Uganda bears a particularly large burden from the disease. Our understanding is limited by a lack of reliable data, but it is clear that the prevalence of malaria infection, incidence of disease, and mortality from severe malaria all remain very high. Uganda has made progress in implementing key malaria control measures, in particular distribution of insecticide impregnated bednets, indoor residual spraying of insecticides, utilization of artemisinin-based combination therapy to treat uncomplicated malaria, and provision of intermittent preventive therapy for pregnant women. However, despite enthusiasm regarding the potential for the elimination of malaria in other areas, there is no convincing evidence that the burden of malaria has decreased in Uganda in recent years. Major challenges to malaria control in Uganda include very high malaria transmission intensity, inadequate health care resources, a weak health system, inadequate understanding of malaria epidemiology and the impact of control interventions, increasing resistance of parasites to drugs and of mosquitoes to insecticides, inappropriate case management, inadequate utilization of drugs to prevent malaria, and inadequate epidemic preparedness and response. Despite these challenges, prospects for the control of malaria have improved, and with attention to underlying challenges, progress toward the control of malaria in Uganda can be expected. PMID:21420377

  5. Movement patterns and spatial segregation of two populations of lake trout Salvelinus namaycush in Lake Huron

    USGS Publications Warehouse

    Binder, Thomas; Marsden, J. Ellen; Riley, Stephen; Johnson, James E.; Johnson, Nicholas; He, Ji; Ebener, Mark P.; Holbrook, Christopher; Bergstedt, Roger A.; Bronte, Charles R.; Hayden, Todd A.; Krueger, Charles C.

    2017-01-01

    Movement ecology is an important component of life history and population dynamics, and consequently its understanding can inform successful fishery management decision-making. While lake trout populations in Lake Huron have shown signs of recovery from near extinction in recent years, knowledge of their movement behavior remains incomplete. We used acoustic telemetry to describe and compare movement patterns of two Lake Huron lake trout populations: Drummond Island and Thunder Bay. Both populations showed high spawning site fidelity, with no evidence of co-mingling during non-spawning season. Detections between spawning periods were mainly limited to receivers within 100 km of spawning locations, and suggested that the two populations likely remained segregated throughout the year. Drummond Island fish, which spawn inside the Drummond Island Refuge, primarily dispersed east into Canadian waters of Lake Huron, with 79–92% of fish being detected annually on receivers outside the refuge. In contrast, Thunder Bay fish tended to disperse south towards Saginaw Bay. Large proportions (i.e., > 80%) of both populations were available to fisheries outside the management zone containing their spawning location. Thunder Bay fish moved relatively quickly to overwinter habitat after spawning, and tended to repeat the same post-spawning movement behavior each year. The consistent, predictable movement of both populations across management zones highlights the importance of understanding population dynamics to effective management of Lake Huron lake trout.

  6. The watering of tall trees--embolization and recovery.

    PubMed

    Gouin, Henri

    2015-03-21

    We can propound a thermo-mechanical understanding of the ascent of sap to the top of tall trees thanks to a comparison between experiments associated with the cohesion-tension theory and the disjoining pressure concept for liquid thin-films. When a segment of xylem is tight-filled with crude sap, the liquid pressure can be negative although the pressure in embolized vessels remains positive. Examples are given that illustrate how embolized vessels can be refilled and why the ascent of sap is possible even in the tallest trees avoiding the problem due to cavitation. However, the maximum height of trees is limited by the stability domain of liquid thin-films. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. A classification of psychological factors leading to violent behavior in posttraumatic stress disorder.

    PubMed

    Silva, J A; Derecho, D V; Leong, G B; Weinstock, R; Ferrari, M M

    2001-03-01

    Posttraumatic stress disorder has long been linked to violent behavior. However, the exact nature of that association remains poorly characterized due to the limitations of knowledge in the area of phenomenology, contextual factors, the biology, and the nature of the aggression involved in the disorder. A clear understanding of the genesis of violence in posttraumatic stress disorder can be helpful to those involved in assessing psychiatric-legal issues relevant to the disorder and in its therapeutic management. In this article, we review the potential psychological links between posttraumatic stress disorder secondary to combat exposure and violent behavior and suggest a tentative classification of the main psychological causes of violence in that syndrome.

  8. Flea control failure? Myths and realities.

    PubMed

    Halos, Lénaïg; Beugnet, Frédéric; Cardoso, Luís; Farkas, Robert; Franc, Michel; Guillot, Jacques; Pfister, Kurt; Wall, Richard

    2014-05-01

    Why is it that, despite the proliferation of research on their biology and control, fleas remain such a burden for companion animals and their owners? This review highlights a range of reasons for persistence and apparent treatment failures. It argues that a sustainable approach will require integrated pest management based upon a detailed understanding of the flea life cycle, targeting not only adult fleas but also the immature stages in the environment, combining several modes of control and limiting the risk of chemoresistance. Individual characteristics of the pet and its environment need to be considered. Control of fleas can be achieved, over a timescale of several months, if basic rules are respected. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Interface between Intellectual Disability and Mental Health: hermeneutic review

    PubMed Central

    Surjus, Luciana Togni de Lima e Silva; Campos, Rosana Teresa Onocko

    2014-01-01

    A literature review was conducted aiming to understand the interface between the Intellectual Disability and Mental Health fields and to contribute to mitigating the path of institutionalizing individuals with intellectual deficiencies. The so-called dual diagnosis phenomenon remains underestimated in Brazil but is the object of research and specific public policy internationally. This phenomenon alerts us to the prevalence of mental health problems in those with intellectual disabilities, limiting their social inclusion. The findings reinforce the importance of this theme and indicate possible diagnostic invisibility of the development of mental illness in those with intellectual disabilities in Brazil, which may contribute to sustaining psychiatric institutionalization of this population.  PMID:25119948

  10. Towards the identification of the loci of adaptive evolution

    PubMed Central

    Pardo-Diaz, Carolina; Salazar, Camilo; Jiggins, Chris D

    2015-01-01

    1. Establishing the genetic and molecular basis underlying adaptive traits is one of the major goals of evolutionary geneticists in order to understand the connection between genotype and phenotype and elucidate the mechanisms of evolutionary change. Despite considerable effort to address this question, there remain relatively few systems in which the genes shaping adaptations have been identified. 2. Here, we review the experimental tools that have been applied to document the molecular basis underlying evolution in several natural systems, in order to highlight their benefits, limitations and suitability. In most cases, a combination of DNA, RNA and functional methodologies with field experiments will be needed to uncover the genes and mechanisms shaping adaptation in nature. PMID:25937885

  11. Rodent Auditory Perception: Critical Band Limitations and Plasticity

    PubMed Central

    King, Julia; Insanally, Michele; Jin, Menghan; Martins, Ana Raquel O.; D'amour, James A.; Froemke, Robert C.

    2015-01-01

    What do animals hear? While it remains challenging to adequately assess sensory perception in animal models, it is important to determine perceptual abilities in model systems to understand how physiological processes and plasticity relate to perception, learning, and cognition. Here we discuss hearing in rodents, reviewing previous and recent behavioral experiments querying acoustic perception in rats and mice, and examining the relation between behavioral data and electrophysiological recordings from the central auditory system. We focus on measurements of critical bands, which are psychoacoustic phenomena that seem to have a neural basis in the functional organization of the cochlea and the inferior colliculus. We then discuss how behavioral training, brain stimulation, and neuropathology impact auditory processing and perception. PMID:25827498

  12. Glanders: off to the races with Burkholderia mallei.

    PubMed

    Whitlock, Gregory C; Estes, D Mark; Torres, Alfredo G

    2007-12-01

    Burkholderia mallei, the etiologic agent of the disease known as glanders, is primarily a disease affecting horses and is transmitted to humans by direct contact with infected animals. The use of B. mallei as a biological weapon has been reported and currently, there is no vaccine available for either humans or animals. Despite the history and highly infective nature of B. mallei, as well as its potential use as a bio-weapon, B. mallei research to understand the pathogenesis and the host responses to infection remains limited. Therefore, this minireview will focus on current efforts to elucidate B. mallei virulence, the associated host immune responses elicited during infection and discuss the feasibility of vaccine development.

  13. An abyssal mobilome: viruses, plasmids and vesicles from deep-sea hydrothermal vents.

    PubMed

    Lossouarn, Julien; Dupont, Samuel; Gorlas, Aurore; Mercier, Coraline; Bienvenu, Nadege; Marguet, Evelyne; Forterre, Patrick; Geslin, Claire

    2015-12-01

    Mobile genetic elements (MGEs) such as viruses, plasmids, vesicles, gene transfer agents (GTAs), transposons and transpovirions, which collectively represent the mobilome, interact with cellular organisms from all three domains of life, including those thriving in the most extreme environments. While efforts have been made to better understand deep-sea vent microbial ecology, our knowledge of the mobilome associated with prokaryotes inhabiting deep-sea hydrothermal vents remains limited. Here we focus on the abyssal mobilome by reviewing accumulating data on viruses, plasmids and vesicles associated with thermophilic and hyperthermophilic Bacteria and Archaea present in deep-sea hydrothermal vents. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  14. Prognostic modelling options for remaining useful life estimation by industry

    NASA Astrophysics Data System (ADS)

    Sikorska, J. Z.; Hodkiewicz, M.; Ma, L.

    2011-07-01

    Over recent years a significant amount of research has been undertaken to develop prognostic models that can be used to predict the remaining useful life of engineering assets. Implementations by industry have only had limited success. By design, models are subject to specific assumptions and approximations, some of which are mathematical, while others relate to practical implementation issues such as the amount of data required to validate and verify a proposed model. Therefore, appropriate model selection for successful practical implementation requires not only a mathematical understanding of each model type, but also an appreciation of how a particular business intends to utilise a model and its outputs. This paper discusses business issues that need to be considered when selecting an appropriate modelling approach for trial. It also presents classification tables and process flow diagrams to assist industry and research personnel select appropriate prognostic models for predicting the remaining useful life of engineering assets within their specific business environment. The paper then explores the strengths and weaknesses of the main prognostics model classes to establish what makes them better suited to certain applications than to others and summarises how each have been applied to engineering prognostics. Consequently, this paper should provide a starting point for young researchers first considering options for remaining useful life prediction. The models described in this paper are Knowledge-based (expert and fuzzy), Life expectancy (stochastic and statistical), Artificial Neural Networks, and Physical models.

  15. Plastid proteomics for elucidating iron limited remodeling of plastid physiology in diatoms

    NASA Astrophysics Data System (ADS)

    Gomes, K. M.; Nunn, B. L.; Jenkins, B. D.

    2016-02-01

    Diatoms are important primary producers in the world's oceans and their growth is constrained in large regions by low iron availability. This low iron-induced limitation of primary production is due to the requirement for iron in components of essential metabolic pathways including key chloroplast functions such as photosynthesis and nitrate assimilation. Diatoms can bloom and accumulate high biomass during introduction of iron into low iron waters, indicating adaptations allowing for their survival in iron-limited waters and rapid growth when iron becomes more abundant. Prior studies have shown that under iron limited stress, diatoms alter plastid-specific processes including components of electron transport, size of light harvesting capacity and chlorophyll content, suggesting plastid-specific protein regulation. Due to their complex evolutionary history, resulting from a secondary endosymbiosis, knowledge regarding the complement of plastid localized proteins remains limited in comparison to other model photosynthetic organisms. While in-silico prediction of diatom protein localization provides putative candidates for plastid-localization, these analyses can be limited as most plastid prediction models were developed using plants, primary endosymbionts. In order to characterize proteins enriched in diatom chloroplast and to understand how the plastid proteome is remodeled in response to iron limitation, we used mass spectrometry based proteomics to compare plastid- enriched protein fractions from Thalassiosira pseudonana, grown in iron replete and limited conditions. These analyses show that iron stress alters regulation of major metabolic pathways in the plastid including the Calvin cycle and fatty acid synthesis. These components provide promising targets to further characterize the plastid specific response to iron limitation.

  16. Identification of Fitness Determinants during Energy-Limited Growth Arrest in Pseudomonas aeruginosa.

    PubMed

    Basta, David W; Bergkessel, Megan; Newman, Dianne K

    2017-11-28

    Microbial growth arrest can be triggered by diverse factors, one of which is energy limitation due to scarcity of electron donors or acceptors. Genes that govern fitness during energy-limited growth arrest and the extent to which they overlap between different types of energy limitation are poorly defined. In this study, we exploited the fact that Pseudomonas aeruginosa can remain viable over several weeks when limited for organic carbon (pyruvate) as an electron donor or oxygen as an electron acceptor. ATP values were reduced under both types of limitation, yet more severely in the absence of oxygen. Using transposon-insertion sequencing (Tn-seq), we identified fitness determinants in these two energy-limited states. Multiple genes encoding general functions like transcriptional regulation and energy generation were required for fitness during carbon or oxygen limitation, yet many specific genes, and thus specific activities, differed in their relevance between these states. For instance, the global regulator RpoS was required during both types of energy limitation, while other global regulators such as DksA and LasR were required only during carbon or oxygen limitation, respectively. Similarly, certain ribosomal and tRNA modifications were specifically required during oxygen limitation. We validated fitness defects during energy limitation using independently generated mutants of genes detected in our screen. Mutants in distinct functional categories exhibited different fitness dynamics: regulatory genes generally manifested a phenotype early, whereas genes involved in cell wall metabolism were required later. Together, these results provide a new window into how P. aeruginosa survives growth arrest. IMPORTANCE Growth-arrested bacteria are ubiquitous in nature and disease yet understudied at the molecular level. For example, growth-arrested cells constitute a major subpopulation of mature biofilms, serving as an antibiotic-tolerant reservoir in chronic infections. Identification of the genes required for survival of growth arrest (encompassing entry, maintenance, and exit) is an important first step toward understanding the physiology of bacteria in this state. Using Tn-seq, we identified and validated genes required for fitness of Pseudomonas aeruginosa when energy limited for organic carbon or oxygen, which represent two common causes of growth arrest for P. aeruginosa in diverse habitats. This unbiased, genome-wide survey is the first to reveal essential activities for a pathogen experiencing different types of energy limitation, finding both shared and divergent activities that are relevant at different survival stages. Future efforts can now be directed toward understanding how the biomolecules responsible for these activities contribute to fitness under these conditions. Copyright © 2017 Basta et al.

  17. White-nose syndrome detected in bats over an extensive area of Russia.

    PubMed

    Kovacova, Veronika; Zukal, Jan; Bandouchova, Hana; Botvinkin, Alexander D; Harazim, Markéta; Martínková, Natália; Orlov, Oleg L; Piacek, Vladimir; Shumkina, Alexandra P; Tiunov, Mikhail P; Pikula, Jiri

    2018-06-18

    Spatiotemporal distribution patterns are important infectious disease epidemiological characteristics that improve our understanding of wild animal population health. The skin infection caused by the fungus Pseudogymnoascus destructans emerged as a panzootic disease in bats of the northern hemisphere. However, the infection status of bats over an extensive geographic area of the Russian Federation has remained understudied. We examined bats at the geographic limits of bat hibernation in the Palearctic temperate zone and found bats with white-nose syndrome (WNS) on the European slopes of the Ural Mountains through the Western Siberian Plain, Central Siberia and on to the Far East. We identified the diagnostic symptoms of WNS based on histopathology in the Northern Ural region at 11° (about 1200 km) higher latitude than the current northern limit in the Nearctic. While body surface temperature differed between regions, bats at all study sites hibernated in very cold conditions averaging 3.6 °C. Each region also differed in P. destructans fungal load and the number of UV fluorescent skin lesions indicating skin damage intensity. Myotis bombinus, M. gracilis and Murina hilgendorfi were newly confirmed with histopathological symptoms of WNS. Prevalence of UV-documented WNS ranged between 16 and 76% in species of relevant sample size. To conclude, the bat pathogen P. destructans is widely present in Russian hibernacula but infection remains at low intensity, despite the high exposure rate.

  18. Precision-cut liver slices to investigate responsiveness of deep-sea fish to contaminants at high pressure.

    PubMed

    Lemaire, Benjamin; Debier, Cathy; Calderon, Pedro Buc; Thomé, Jean Pierre; Stegeman, John; Mork, Jarle; Rees, Jean François

    2012-09-18

    While deep-sea fish accumulate high levels of persistent organic pollutants (POPs), the toxicity associated with this contamination remains unknown. Indeed, the recurrent collection of moribund individuals precludes experimental studies to investigate POP effects in this fauna. We show that precision-cut liver slices (PCLS), an in vitro tool commonly used in human and rodent toxicology, can overcome such limitation. This technology was applied to individuals of the deep-sea grenadier Coryphaenoides rupestris directly upon retrieval from 530-m depth in Trondheimsfjord (Norway). PCLS remained viable and functional for 15 h when maintained in an appropriate culture media at 4 °C. This allowed experimental exposure of liver slices to the model POP 3-methylcholanthrene (3-MC; 25 μM) at levels of hydrostatic pressure mimicking shallow (0.1 megapascal or MPa) and deep-sea (5-15 MPa; representative of 500-1500 m depth) environments. As in shallow water fish, 3-MC induced the transcription of the detoxification enzyme cytochrome P4501A (CYP1A; a biomarker of exposure to POPs). This induction was diminished at elevated pressure, suggesting a limited responsiveness of C. rupestris toward POPs in its native environment. This very first in vitro toxicological investigation on a deep-sea fish opens the route for understanding pollutants effects in this highly exposed fauna.

  19. Three-dimensional morphology of CuInS2:P3HT hybrid blends for photovoltaic applications

    NASA Astrophysics Data System (ADS)

    Krause, Christopher; Scheunemann, Dorothea; Parisi, Jürgen; Borchert, Holger

    2015-11-01

    Despite potential advantages, the performance of hybrid solar cells with colloidal nanocrystals remains low compared to pure organic solar cells, in particular, when Cd- and Pb-free nanocrystals are employed. To understand this discrepancy, we analyzed possible limiting factors of the performance of hybrid solar cells with CuInS2 nanoparticles and the polymer poly(3-hexylthiophene) (P3HT). Optimizing the thickness of the active layer indicated that charge transport limits the performance of the solar cells. Since charge transport is among others influenced by the morphology of the bulk heterojunction layer, we performed a detailed analysis of the blend morphology. Therefore, we used electron tomography which provides three-dimensional information on the interpenetrating network formed by the hybrid CuInS2:P3HT system. Using statistical methods, we analyzed the distribution of the nanoparticles inside the polymer matrix and the structure of the percolation paths. We found that the morphology appears well suited for application in hybrid solar cells, meaning that other factors must be the bottleneck. Therefore, we investigated in a second step the influence of a post-deposition ligand exchange with acetic acid. This strategy resulted in a strong relative improvement of the solar cell performance, although absolute performance parameters remain low in comparison to hybrid solar cells with colloidal cadmium or lead chalcogenide nanocrystals.

  20. Systems analysis of phosphate-limitation-induced lipid accumulation by the oleaginous yeast Rhodosporidium toruloides.

    PubMed

    Wang, Yanan; Zhang, Sufang; Zhu, Zhiwei; Shen, Hongwei; Lin, Xinping; Jin, Xiang; Jiao, Xiang; Zhao, Zongbao Kent

    2018-01-01

    Lipid accumulation by oleaginous microorganisms is of great scientific interest and biotechnological potential. While nitrogen limitation has been routinely employed, low-cost raw materials usually contain rich nitrogenous components, thus preventing from efficient lipid production. Inorganic phosphate (Pi) limitation has been found sufficient to promote conversion of sugars into lipids, yet the molecular basis of cellular response to Pi limitation and concurrent lipid accumulation remains elusive. Here, we performed multi-omic analyses of the oleaginous yeast Rhodosporidium toruloides to shield lights on Pi-limitation-induced lipid accumulation. Samples were prepared under Pi-limited as well as Pi-repleted chemostat conditions, and subjected to analysis at the transcriptomic, proteomic, and metabolomic levels. In total, 7970 genes, 4212 proteins, and 123 metabolites were identified. Results showed that Pi limitation facilitates up-regulation of Pi-associated metabolism, RNA degradation, and triacylglycerol biosynthesis while down-regulation of ribosome biosynthesis and tricarboxylic acid cycle. Pi limitation leads to dephosphorylation of adenosine monophosphate and the allosteric activator of isocitrate dehydrogenase key to lipid biosynthesis. It was found that NADPH, the key cofactor for fatty acid biosynthesis, is limited due to reduced flux through the pentose phosphate pathway and transhydrogenation cycle and that this can be overcome by over-expression of an endogenous malic enzyme. These phenomena are found distinctive from those under nitrogen limitation. Our data suggest that Pi limitation activates Pi-related metabolism, RNA degradation, and TAG biosynthesis while inhibits ribosome biosynthesis and TCA cycle, leading to enhanced carbon fluxes into lipids. The information greatly enriches our understanding on microbial oleaginicity and Pi-related metabolism. Importantly, systems data may facilitate designing advanced cell factories for production of lipids and related oleochemicals.

  1. Competition for nutrients and light: testing advances in resource competition with a natural phytoplankton community.

    PubMed

    Burson, Amanda; Stomp, Maayke; Greenwell, Emma; Grosse, Julia; Huisman, Jef

    2018-05-01

    A key challenge in ecology is to understand how nutrients and light affect the biodiversity and community structure of phytoplankton and plant communities. According to resource competition models, ratios of limiting nutrients are major determinants of species composition. At high nutrient levels, however, species interactions may shift to competition for light, which might make nutrient ratios less relevant. The "nutrient-load hypothesis" merges these two perspectives, by extending the classic model of competition for two nutrients to include competition for light. Here, we test five key predictions of the nutrient-load hypothesis using multispecies competition experiments. A marine phytoplankton community sampled from the North Sea was inoculated in laboratory chemostats provided with different nitrogen (N) and phosphorus (P) loads to induce either single resource limitation or co-limitation of N, P, and light. Four of the five predictions were validated by the experiments. In particular, different resource limitations favored the dominance of different species. Increasing nutrient loads caused changes in phytoplankton species composition, even if the N:P ratio of the nutrient loads remained constant, by shifting the species interactions from competition for nutrients to competition for light. In all treatments, small species became dominant whereas larger species were competitively excluded, supporting the common view that small cell size provides a competitive advantage under resource-limited conditions. Contrary to expectation, all treatments led to coexistence of diatoms, cyanobacteria and green algae, resulting in a higher diversity of species than predicted by theory. Because the coexisting species comprised three phyla with different photosynthetic pigments, we speculate that niche differentiation in the light spectrum might play a role. Our results show that mechanistic resource competition models that integrate nutrient-based and light-based approaches provide an important step forward to understand and predict how changing nutrient loads affect community composition. © 2018 The Authors Ecology published by Wiley Periodicals, Inc. on behalf of Ecological Society of America.

  2. Understanding How Race/Ethnicity and Gender Define Age-Trajectories of Disability: An Intersectionality Approach

    PubMed Central

    Warner, David F.; Brown, Tyson H.

    2011-01-01

    A number of studies have demonstrated wide disparities in health among racial/ethnic groups and by gender, yet few have examined how race/ethnicity and gender intersect or combine to affect the health of older adults. The tendency of prior research to treat race/ethnicity and gender separately has potentially obscured important differences in how health is produced and maintained, undermining efforts to eliminate health disparities. The current study extends previous research by taking an intersectionality approach (Mullings & Schulz, 2006), grounded in life course theory, conceptualizing and modeling trajectories of functional limitations as dynamic life course processes that are jointly and simultaneously defined by race/ethnicity and gender. Data from the nationally representative 1994–2006 US Health and Retirement Study and growth curve models are utilized to examine racial/ethnic/gender differences in intra-individual change in functional limitations among White, Black and Mexican American Men and Women, and the extent to which differences in life course capital account for group disparities in initial health status and rates of change with age. Results support an intersectionality approach, with all demographic groups exhibiting worse functional limitation trajectories than White Men. Whereas White Men had the lowest disability levels at baseline, White Women and racial/ethnic minority Men had intermediate disability levels and Black and Hispanic Women had the highest disability levels. These health disparities remained stable with age—except among Black Women who experience a trajectory of accelerated disablement. Dissimilar early life social origins, adult socioeconomic status, marital status, and health behaviors explain the racial/ethnic disparities in functional limitations among Men but only partially explain the disparities among Women. Net of controls for life course capital, Women of all racial/ethnic groups have higher levels of functional limitations relative to White Men and Men of the same race/ethnicity. Findings highlight the utility of an intersectionality approach to understanding health disparities. PMID:21470737

  3. Understanding how race/ethnicity and gender define age-trajectories of disability: an intersectionality approach.

    PubMed

    Warner, David F; Brown, Tyson H

    2011-04-01

    A number of studies have demonstrated wide disparities in health among racial/ethnic groups and by gender, yet few have examined how race/ethnicity and gender intersect or combine to affect the health of older adults. The tendency of prior research to treat race/ethnicity and gender separately has potentially obscured important differences in how health is produced and maintained, undermining efforts to eliminate health disparities. The current study extends previous research by taking an intersectionality approach (Mullings & Schulz, 2006), grounded in life course theory, conceptualizing and modeling trajectories of functional limitations as dynamic life course processes that are jointly and simultaneously defined by race/ethnicity and gender. Data from the nationally representative 1994-2006 US Health and Retirement Study and growth curve models are utilized to examine racial/ethnic/gender differences in intra-individual change in functional limitations among White, Black and Mexican American Men and Women, and the extent to which differences in life course capital account for group disparities in initial health status and rates of change with age. Results support an intersectionality approach, with all demographic groups exhibiting worse functional limitation trajectories than White Men. Whereas White Men had the lowest disability levels at baseline, White Women and racial/ethnic minority Men had intermediate disability levels and Black and Hispanic Women had the highest disability levels. These health disparities remained stable with age-except among Black Women who experience a trajectory of accelerated disablement. Dissimilar early life social origins, adult socioeconomic status, marital status, and health behaviors explain the racial/ethnic disparities in functional limitations among Men but only partially explain the disparities among Women. Net of controls for life course capital, Women of all racial/ethnic groups have higher levels of functional limitations relative to White Men and Men of the same race/ethnicity. Findings highlight the utility of an intersectionality approach to understanding health disparities. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Dissecting Redox Biology Using Fluorescent Protein Sensors.

    PubMed

    Schwarzländer, Markus; Dick, Tobias P; Meyer, Andreas J; Morgan, Bruce

    2016-05-01

    Fluorescent protein sensors have revitalized the field of redox biology by revolutionizing the study of redox processes in living cells and organisms. Within one decade, a set of fundamental new insights has been gained, driven by the rapid technical development of in vivo redox sensing. Redox-sensitive yellow and green fluorescent protein variants (rxYFP and roGFPs) have been the central players. Although widely used as an established standard tool, important questions remain surrounding their meaningful use in vivo. We review the growing range of thiol redox sensor variants and their application in different cells, tissues, and organisms. We highlight five key findings where in vivo sensing has been instrumental in changing our understanding of redox biology, critically assess the interpretation of in vivo redox data, and discuss technical and biological limitations of current redox sensors and sensing approaches. We explore how novel sensor variants may further add to the current momentum toward a novel mechanistic and integrated understanding of redox biology in vivo. Antioxid. Redox Signal. 24, 680-712.

  5. Future perspective of induced pluripotent stem cells for diagnosis, drug screening and treatment of human diseases.

    PubMed

    Lian, Qizhou; Chow, Yenyen; Esteban, Miguel Angel; Pei, Duanqing; Tse, Hung-Fat

    2010-07-01

    Recent advances in stem cell biology have transformed the understanding of cell physiology and developmental biology such that it can now play a more prominent role in the clinical application of stem cell and regenerative medicine. Success in the generation of human induced pluripotent stem cells (iPS) as well as related emerging technology on the iPS platform provide great promise in the development of regenerative medicine. Human iPS cells show almost identical properties to human embryonic stem cells (ESC) in pluripotency, but avoid many of their limitations of use. In addition, investigations into reprogramming of somatic cells to pluripotent stem cells facilitate a deeper understanding of human stem cell biology. The iPS cell technology has offered a unique platform for studying the pathogenesis of human disease, pharmacological and toxicological testing, and cell-based therapy. Nevertheless, significant challenges remain to be overcome before the promise of human iPS cell technology can be realised.

  6. Plastic ingestion in marine-associated bird species from the eastern North Pacific.

    PubMed

    Avery-Gomm, S; Provencher, J F; Morgan, K H; Bertram, D F

    2013-07-15

    In addition to monitoring trends in plastic pollution, multi-species surveys are needed to fully understand the pervasiveness of plastic ingestion. We examined the stomach contents of 20 bird species collected from the coastal waters of the eastern North Pacific, a region known to have high levels of plastic pollution. We observed no evidence of plastic ingestion in Rhinoceros Auklet, Marbled Murrelet, Ancient Murrelet or Pigeon Guillemot, and low levels in Common Murre (2.7% incidence rate). Small sample sizes limit our ability to draw conclusions about population level trends for the remaining fifteen species, though evidence of plastic ingestion was found in Glaucous-Winged Gull and Sooty Shearwater. Documenting levels of plastic ingestion in a wide array of species is necessary to gain a comprehensive understanding about the impacts of plastic pollution. We propose that those working with bird carcasses follow standard protocols to assess the levels of plastic ingestion whenever possible. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Stress and Cognition: A Cognitive Psychological Perspective

    NASA Technical Reports Server (NTRS)

    Bourne, Lyle E., Jr.; Yaroush, Rita A.

    2003-01-01

    Research in cognitive psychology has made a significant contribution to our understanding of how acute and chronic stress affect performance. It has done so by identifying some of the factors that contribute to operator error and by suggesting how operators might be trained to respond more effectively in a variety of circumstances. The major purpose of this paper was to review the literature of cognitive psychology as it relates to these questions and issues. Based on the existence of earlier reviews (e.g., Hamilton, & Warburton, 1979; Hockey, 1983) the following investigation was limited to the last 15 years (1988-2002) and restricted to a review of the primary peer-reviewed literature. The results of this examination revealed that while cognitive psychology has contributed in a substantive way to our understanding of stress impact on various cognitive processes, it has also left many questions unanswered. Concerns about how we define and use the term stress and the gaps that remain in our knowledge about the specific effects of stressors on cognitive processes are discussed in the text.

  8. Mechanism for rapid growth of organic–inorganic halide perovskite crystals

    DOE PAGES

    Nayak, Pabitra K.; Moore, David T.; Wenger, Bernard; ...

    2016-11-10

    Optoelectronic devices based on hybrid halide perovskites have shown remarkable progress to high performance. However, despite their apparent success, there remain many open questions about their intrinsic properties. Single crystals are often seen as the ideal platform for understanding the limits of crystalline materials, and recent reports of rapid, high-temperature crystallization of single crystals should enable a variety of studies. Here we explore the mechanism of this crystallization and find that it is due to reversible changes in the solution where breaking up of colloids, and a change in the solvent strength, leads to supersaturation and subsequent crystallization. Here, wemore » use this knowledge to demonstrate a broader range of processing parameters and show that these can lead to improved crystal quality. Lastly, our findings are therefore of central importance to enable the continued advancement of perovskite optoelectronics and to the improved reproducibility through a better understanding of factors influencing and controlling crystallization.« less

  9. A mother cell-to-forespore channel: current understanding and future challenges.

    PubMed

    Crawshaw, Adam D; Serrano, Mónica; Stanley, Will A; Henriques, Adriano O; Salgado, Paula S

    2014-09-01

    Formation of endospores allows some bacteria to survive extreme nutrient limitation. The resulting dormant cell, the spore, persists in the environment and is highly resistant to physical and chemical stresses. During spore formation, cells divide asymmetrically and the mother cell engulfs the developing spore, encasing it within a double membrane and isolating it from the medium. Communication between mother cell and isolated forespore involves a specialised connection system that allows nurturing of the forespore and continued macromolecular synthesis, required to finalise spore maturation. Here, we review current understanding of this feeding channel formed by a forespore protein, SpoIIQ, and a mother cell protein, SpoIIIAH, in the model organism Bacillus subtilis and the important human pathogen Clostridium difficile. We also analyse the presence of this channel across endospore-forming bacteria and highlight the main questions still remaining. © 2014 The Authors FEMS Microbiology Letters published by John Wiley & Sons Ltd on behalf of Federation of European Microbiological Societies.

  10. Epidemiology and population biology of Pseudoperonospora cubensis: a model system for management of downy mildews.

    PubMed

    Ojiambo, Peter S; Gent, David H; Quesada-Ocampo, Lina M; Hausbeck, Mary K; Holmes, Gerald J

    2015-01-01

    The resurgence of cucurbit downy mildew has dramatically influenced production of cucurbits and disease management systems at multiple scales. Long-distance dispersal is a fundamental aspect of epidemic development that influences the timing and extent of outbreaks of cucurbit downy mildew. The dispersal potential of Pseudoperonospora cubensis appears to be limited primarily by sporangia production in source fields and availability of susceptible hosts and less by sporangia survival during transport. Uncertainty remains regarding the role of locally produced inoculum in disease outbreaks, but evidence suggests multiple sources of primary inoculum could be important. Understanding pathogen diversity and population differentiation is a critical aspect of disease management and an active research area. Underpinning advances in our understanding of pathogen biology and disease management has been the research capacity and coordination of stakeholders, scientists, and extension personnel. Concepts and approaches developed in this pathosystem can guide future efforts when responding to incursions of new or reemerging downy mildew pathogens.

  11. Current Approaches, Challenges and Future Directions for Monitoring Treatment Response in Prostate Cancer

    PubMed Central

    Wallace, T.J.; Torre, T.; Grob, M.; Yu, J.; Avital, I.; Brücher, BLDM; Stojadinovic, A.; Man, Y.G.

    2014-01-01

    Prostate cancer is the most commonly diagnosed non-cutaneous neoplasm in men in the United States and the second leading cause of cancer mortality. One in 7 men will be diagnosed with prostate cancer during their lifetime. As a result, monitoring treatment response is of vital importance. The cornerstone of current approaches in monitoring treatment response remains the prostate-specific antigen (PSA). However, with the limitations of PSA come challenges in our ability to monitor treatment success. Defining PSA response is different depending on the individual treatment rendered potentially making it difficult for those not trained in urologic oncology to understand. Furthermore, standard treatment response criteria do not apply to prostate cancer further complicating the issue of treatment response. Historically, prostate cancer has been difficult to image and no single modality has been consistently relied upon to measure treatment response. However, with newer imaging modalities and advances in our understanding and utilization of specific biomarkers, the future for monitoring treatment response in prostate cancer looks bright. PMID:24396494

  12. Change in the magnitude and mechanisms of global temperature variability with warming

    PubMed Central

    Brown, Patrick T.; Ming, Yi; Li, Wenhong; Hill, Spencer A.

    2017-01-01

    Natural unforced variability in global mean surface air temperature (GMST) can mask or exaggerate human-caused global warming, and thus a complete understanding of this variability is highly desirable. Significant progress has been made in elucidating the magnitude and physical origins of present-day unforced GMST variability, but it has remained unclear how such variability may change as the climate warms. Here we present modeling evidence that indicates that the magnitude of low-frequency GMST variability is likely to decline in a warmer climate and that its generating mechanisms may be fundamentally altered. In particular, a warmer climate results in lower albedo at high latitudes, which yields a weaker albedo feedback on unforced GMST variability. These results imply that unforced GMST variability is dependent on the background climatological conditions, and thus climate model control simulations run under perpetual preindustrial conditions may have only limited relevance for understanding the unforced GMST variability of the future. PMID:29391875

  13. A genomic approach to identify hybrid incompatibility genes

    PubMed Central

    Cooper, Jacob C.; Phadnis, Nitin

    2016-01-01

    ABSTRACT Uncovering the genetic and molecular basis of barriers to gene flow between populations is key to understanding how new species are born. Intrinsic postzygotic reproductive barriers such as hybrid sterility and hybrid inviability are caused by deleterious genetic interactions known as hybrid incompatibilities. The difficulty in identifying these hybrid incompatibility genes remains a rate-limiting step in our understanding of the molecular basis of speciation. We recently described how whole genome sequencing can be applied to identify hybrid incompatibility genes, even from genetically terminal hybrids. Using this approach, we discovered a new hybrid incompatibility gene, gfzf, between Drosophila melanogaster and Drosophila simulans, and found that it plays an essential role in cell cycle regulation. Here, we discuss the history of the hunt for incompatibility genes between these species, discuss the molecular roles of gfzf in cell cycle regulation, and explore how intragenomic conflict drives the evolution of fundamental cellular mechanisms that lead to the developmental arrest of hybrids. PMID:27230814

  14. Conducting interface in oxide homojunction: Understanding of superior properties in black TiO 2

    DOE PAGES

    Lu, Xujie; Chen, Aiping; Luo, Yongkang; ...

    2016-09-14

    Black TiO 2 nanoparticles with a crystalline core and amorphous-shell structure exhibit superior optoelectronic properties in comparison with pristine TiO 2. The fundamental mechanisms underlying these enhancements, however, remain unclear, largely due to the inherent complexities and limitations of powder materials. Here, we fabricate TiO 2 homojunction films consisting of an oxygen-deficient amorphous layer on top of a highly crystalline layer, to simulate the structural/functional configuration of black TiO 2 nanoparticles. Metallic conduction is achieved at the crystalline–amorphous homointerface via electronic interface reconstruction, which we show to be the main reason for the enhanced electron transport of black TiO 2.more » As a result, this work not only achieves an unprecedented understanding of black TiO 2 but also provides a new perspective for investigating carrier generation and transport behavior at oxide interfaces, which are of tremendous fundamental and technological interest.« less

  15. Atomistic origin of an ordered superstructure induced superconductivity in layered chalcogenides.

    PubMed

    Ang, R; Wang, Z C; Chen, C L; Tang, J; Liu, N; Liu, Y; Lu, W J; Sun, Y P; Mori, T; Ikuhara, Y

    2015-01-27

    Interplay among various collective electronic states such as charge density wave and superconductivity is of tremendous significance in low-dimensional electron systems. However, the atomistic and physical nature of the electronic structures underlying the interplay of exotic states, which is critical to clarifying its effect on remarkable properties of the electron systems, remains elusive, limiting our understanding of the superconducting mechanism. Here, we show evidence that an ordering of selenium and sulphur atoms surrounding tantalum within star-of-David clusters can boost superconductivity in a layered chalcogenide 1T-TaS2-xSex, which undergoes a superconducting transition in the nearly commensurate charge density wave phase. Advanced electron microscopy investigations reveal that such an ordered superstructure forms only in the x area, where the superconductivity manifests, and is destructible to the occurrence of the Mott metal-insulator transition. The present findings provide a novel dimension in understanding the relationship between lattice and electronic degrees of freedom.

  16. An Ultrathin Nanoporous Membrane Evaporator.

    PubMed

    Lu, Zhengmao; Wilke, Kyle L; Preston, Daniel J; Kinefuchi, Ikuya; Chang-Davidson, Elizabeth; Wang, Evelyn N

    2017-10-11

    Evaporation is a ubiquitous phenomenon found in nature and widely used in industry. Yet a fundamental understanding of interfacial transport during evaporation remains limited to date owing to the difficulty of characterizing the heat and mass transfer at the interface, especially at high heat fluxes (>100 W/cm 2 ). In this work, we elucidated evaporation into an air ambient with an ultrathin (≈200 nm thick) nanoporous (≈130 nm pore diameter) membrane. With our evaporator design, we accurately monitored the temperature of the liquid-vapor interface, reduced the thermal-fluidic transport resistance, and mitigated the clogging risk associated with contamination. At a steady state, we demonstrated heat fluxes of ≈500 W/cm 2 across the interface over a total evaporation area of 0.20 mm 2 . In the high flux regime, we showed the importance of convective transport caused by evaporation itself and that Fick's first law of diffusion no longer applies. This work improves our fundamental understanding of evaporation and paves the way for high flux phase-change devices.

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

    PubMed

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

    2013-12-01

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

  18. Sources and sinks of plastic debris in estuaries: A conceptual model integrating biological, physical and chemical distribution mechanisms.

    PubMed

    Vermeiren, Peter; Muñoz, Cynthia C; Ikejima, Kou

    2016-12-15

    Micro- and macroplastic accumulation threatens estuaries worldwide because of the often dense human populations, diverse plastic inputs and high potential for plastic degradation and storage in these ecosystems. Nonetheless, our understanding of plastic sources and sinks remains limited. We designed conceptual models of the local and estuary-wide transport of plastics. We identify processes affecting the position of plastics in the water column; processes related to the mixing of fresh and salt water; and processes resulting from the influences of wind, topography, and organism-plastic interactions. The models identify gaps in the spatial context of plastic-organisms interactions, the chemical behavior of plastics in estuaries, effects of wind on plastic suspension-deposition cycles, and the relative importance of processes affecting the position in the water column. When interpreted in the context of current understanding, sinks with high management potential can be identified. However, source-sink patterns vary among estuary types and with local scale processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Progressive Learning of Topic Modeling Parameters: A Visual Analytics Framework.

    PubMed

    El-Assady, Mennatallah; Sevastjanova, Rita; Sperrle, Fabian; Keim, Daniel; Collins, Christopher

    2018-01-01

    Topic modeling algorithms are widely used to analyze the thematic composition of text corpora but remain difficult to interpret and adjust. Addressing these limitations, we present a modular visual analytics framework, tackling the understandability and adaptability of topic models through a user-driven reinforcement learning process which does not require a deep understanding of the underlying topic modeling algorithms. Given a document corpus, our approach initializes two algorithm configurations based on a parameter space analysis that enhances document separability. We abstract the model complexity in an interactive visual workspace for exploring the automatic matching results of two models, investigating topic summaries, analyzing parameter distributions, and reviewing documents. The main contribution of our work is an iterative decision-making technique in which users provide a document-based relevance feedback that allows the framework to converge to a user-endorsed topic distribution. We also report feedback from a two-stage study which shows that our technique results in topic model quality improvements on two independent measures.

  20. Pancreatic islet cell therapy for type I diabetes: understanding the effects of glucose stimulation on islets in order to produce better islets for transplantation.

    PubMed

    Ren, Jiaqiang; Jin, Ping; Wang, Ena; Liu, Eric; Harlan, David M; Li, Xin; Stroncek, David F

    2007-01-03

    While insulin replacement remains the cornerstone treatment for type I diabetes mellitus (T1DM), the transplantation of pancreatic islets of Langerhans has the potential to become an important alternative. And yet, islet transplant therapy is limited by several factors, including far too few donor pancreases. Attempts to expand mature islets or to produce islets from stem cells are far from clinical application. The production and expansion of the insulin-producing cells within the islet (so called beta cells), or even creating cells that secrete insulin under appropriate physiological control, has proven difficult. The difficulty is explained, in part, because insulin synthesis and release is complex, unique, and not entirely characterized. Understanding beta-cell function at the molecular level will likely facilitate the development of techniques to manufacture beta-cells from stem cells. We will review islet transplantation, as well as the mechanisms underlying insulin transcription, translation and glucose stimulated insulin release.

  1. Pancreatic islet cell therapy for type I diabetes: understanding the effects of glucose stimulation on islets in order to produce better islets for transplantation

    PubMed Central

    Ren, Jiaqiang; Jin, Ping; Wang, Ena; Liu, Eric; Harlan, David M; Li, Xin; Stroncek, David F

    2007-01-01

    While insulin replacement remains the cornerstone treatment for type I diabetes mellitus (T1DM), the transplantation of pancreatic islets of Langerhans has the potential to become an important alternative. And yet, islet transplant therapy is limited by several factors, including far too few donor pancreases. Attempts to expand mature islets or to produce islets from stem cells are far from clinical application. The production and expansion of the insulin-producing cells within the islet (so called β cells), or even creating cells that secrete insulin under appropriate physiological control, has proven difficult. The difficulty is explained, in part, because insulin synthesis and release is complex, unique, and not entirely characterized. Understanding β-cell function at the molecular level will likely facilitate the development of techniques to manufacture β-cells from stem cells. We will review islet transplantation, as well as the mechanisms underlying insulin transcription, translation and glucose stimulated insulin release. PMID:17201925

  2. Muscle dysmorphia: current insights.

    PubMed

    Tod, David; Edwards, Christian; Cranswick, Ieuan

    2016-01-01

    Since 1997, there has been increasing research focusing on muscle dysmorphia, a condition underpinned by people's beliefs that they have insufficient muscularity, in both the Western and non-Western medical and scientific communities. Much of this empirical interest has surveyed nonclinical samples, and there is limited understanding of people with the condition beyond knowledge about their characteristics. Much of the existing knowledge about people with the condition is unsurprising and inherent in the definition of the disorder, such as dissatisfaction with muscularity and adherence to muscle-building activities. Only recently have investigators started to explore questions beyond these limited tautological findings that may give rise to substantial knowledge advances, such as the examination of masculine and feminine norms. There is limited understanding of additional topics such as etiology, prevalence, nosology, prognosis, and treatment. Further, the evidence is largely based on a small number of unstandardized case reports and descriptive studies (involving small samples), which are largely confined to Western (North American, British, and Australian) males. Although much research has been undertaken since the term "muscle dysmorphia" entered the psychiatric lexicon in 1997, there remains tremendous scope for knowledge advancement. A primary task in the short term is for investigators to examine the extent to which the condition exists among well-defined populations to help determine the justification for research funding relative to other public health issues. A greater variety of research questions and designs may contribute to a broader and more robust knowledge base than currently exists. Future work will help clinicians assist a group of people whose quality of life and health are placed at risk by their muscular preoccupation.

  3. Muscle dysmorphia: current insights

    PubMed Central

    Tod, David; Edwards, Christian; Cranswick, Ieuan

    2016-01-01

    Since 1997, there has been increasing research focusing on muscle dysmorphia, a condition underpinned by people’s beliefs that they have insufficient muscularity, in both the Western and non-Western medical and scientific communities. Much of this empirical interest has surveyed nonclinical samples, and there is limited understanding of people with the condition beyond knowledge about their characteristics. Much of the existing knowledge about people with the condition is unsurprising and inherent in the definition of the disorder, such as dissatisfaction with muscularity and adherence to muscle-building activities. Only recently have investigators started to explore questions beyond these limited tautological findings that may give rise to substantial knowledge advances, such as the examination of masculine and feminine norms. There is limited understanding of additional topics such as etiology, prevalence, nosology, prognosis, and treatment. Further, the evidence is largely based on a small number of unstandardized case reports and descriptive studies (involving small samples), which are largely confined to Western (North American, British, and Australian) males. Although much research has been undertaken since the term “muscle dysmorphia” entered the psychiatric lexicon in 1997, there remains tremendous scope for knowledge advancement. A primary task in the short term is for investigators to examine the extent to which the condition exists among well-defined populations to help determine the justification for research funding relative to other public health issues. A greater variety of research questions and designs may contribute to a broader and more robust knowledge base than currently exists. Future work will help clinicians assist a group of people whose quality of life and health are placed at risk by their muscular preoccupation. PMID:27536165

  4. Knowledge and attitudes towards disability in Moldova: A qualitative study of young people's views.

    PubMed

    McLean, Kenneth A; Hardie, Samantha; Paul, Abigail; Paul, Gary; Savage, Iain; Shields, Paul; Symes, Rebecca; Wilson, Joanna; Winstanley, Catherine; Harden, Jeni

    2017-10-01

    People with disabilities in the Republic of Moldova continue to experience considerable discrimination and social exclusion. The Moldovan government recently affirmed their commitment to promote community integration. However, there remains limited evidence to facilitate understanding of these issues, and barriers to the integrative process. This study explored the knowledge and attitudes towards disability of young people within Moldova. A qualitative approach was adopted and 3 semi-structured focus group interviews were conducted with schoolchildren (n = 12), aged 13-15 years. These interviews focussed on different aspects of disability, and community integration. Pictorial and written vignettes were used to stimulate discussion. The interviews were conducted and recorded in Romanian, and were subsequently translated into English to facilitate thematic data analysis. Identified themes included: (1) Knowledge and understanding of disability. The young people's knowledge was limited and framed by the medical model of disability; (2) Attitudes towards community integration. A bias against long-term care institutions, but differing views regarding integration; (3) Perceptions of barriers to community integration: (i) Cultural barriers. Negative, even hostile attitudes towards disability; (ii) Policy barriers. Poor support services; and (iii) Physical barriers. Ongoing issues regarding accessibility. People with disabilities in Moldova experience negative cultural attitudes linked to an outdated conception of disability itself. There are inadequate community support services and infrastructure which act as barriers to inclusion. At present, there can be limited interaction and participation of people with disabilities within local communities, and so few opportunities to refute persistent stereotypes and stigma surrounding disability. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Unveiling the diet of elusive rainforest herbivores in next generation sequencing era? The tapir as a case study.

    PubMed

    Hibert, Fabrice; Taberlet, Pierre; Chave, Jérôme; Scotti-Saintagne, Caroline; Sabatier, Daniel; Richard-Hansen, Cécile

    2013-01-01

    Characterizing the trophic relationships between large herbivores and the outstanding plant diversity in rainforest is a major challenge because of their elusiveness. This is crucial to understand the role of these herbivores in the functioning of the rainforest ecosystems. We tested a non-invasive approach based on the high-throughput sequencing of environmental samples using small plant plastid sequences (the trnL P6 loop) and ribosomal ITS1 primers, referred to as DNA metabarcoding, to investigate the diet of the largest neotropical herbivore, the lowland tapir. Sequencing was performed on plant DNA extracted from tapir faeces collected at the Nouragues station, a protected area of French Guiana. In spite of a limited sampling, our approach reliably provided information about the lowland tapir's diet at this site. Indeed, 95.1% and 74.4% of the plant families and genera identified thanks to the trnL P6 loop, respectively, matched with taxa already known to be consumed by tapirs. With this approach we were able to show that two families and eight new genera are also consumed by the lowland tapir. The taxonomic resolution of this method is limited to the plant family and genera. Complementary barcodes, such as a small portion of ITS1, can be used to efficiently narrow identifications down to the species in some problematic families. We will discuss the remaining limitations of this approach and how useful it is at this stage to unravel the diet of elusive rainforest herbivores and better understand their role as engineers of the ecosystem.

  6. Unveiling the Diet of Elusive Rainforest Herbivores in Next Generation Sequencing Era? The Tapir as a Case Study

    PubMed Central

    Hibert, Fabrice; Taberlet, Pierre; Chave, Jérôme; Scotti-Saintagne, Caroline; Sabatier, Daniel; Richard-Hansen, Cécile

    2013-01-01

    Characterizing the trophic relationships between large herbivores and the outstanding plant diversity in rainforest is a major challenge because of their elusiveness. This is crucial to understand the role of these herbivores in the functioning of the rainforest ecosystems. We tested a non-invasive approach based on the high-throughput sequencing of environmental samples using small plant plastid sequences (the trnL P6 loop) and ribosomal ITS1 primers, referred to as DNA metabarcoding, to investigate the diet of the largest neotropical herbivore, the lowland tapir. Sequencing was performed on plant DNA extracted from tapir faeces collected at the Nouragues station, a protected area of French Guiana. In spite of a limited sampling, our approach reliably provided information about the lowland tapir's diet at this site. Indeed, 95.1% and 74.4% of the plant families and genera identified thanks to the trnL P6 loop, respectively, matched with taxa already known to be consumed by tapirs. With this approach we were able to show that two families and eight new genera are also consumed by the lowland tapir. The taxonomic resolution of this method is limited to the plant family and genera. Complementary barcodes, such as a small portion of ITS1, can be used to efficiently narrow identifications down to the species in some problematic families. We will discuss the remaining limitations of this approach and how useful it is at this stage to unravel the diet of elusive rainforest herbivores and better understand their role as engineers of the ecosystem. PMID:23560107

  7. Stationary moments, diffusion limits, and extinction times for logistic growth with random catastrophes.

    PubMed

    Schlomann, Brandon H

    2018-06-06

    A central problem in population ecology is understanding the consequences of stochastic fluctuations. Analytically tractable models with Gaussian driving noise have led to important, general insights, but they fail to capture rare, catastrophic events, which are increasingly observed at scales ranging from global fisheries to intestinal microbiota. Due to mathematical challenges, growth processes with random catastrophes are less well characterized and it remains unclear how their consequences differ from those of Gaussian processes. In the face of a changing climate and predicted increases in ecological catastrophes, as well as increased interest in harnessing microbes for therapeutics, these processes have never been more relevant. To better understand them, I revisit here a differential equation model of logistic growth coupled to density-independent catastrophes that arrive as a Poisson process, and derive new analytic results that reveal its statistical structure. First, I derive exact expressions for the model's stationary moments, revealing a single effective catastrophe parameter that largely controls low order statistics. Then, I use weak convergence theorems to construct its Gaussian analog in a limit of frequent, small catastrophes, keeping the stationary population mean constant for normalization. Numerically computing statistics along this limit shows how they transform as the dynamics shifts from catastrophes to diffusions, enabling quantitative comparisons. For example, the mean time to extinction increases monotonically by orders of magnitude, demonstrating significantly higher extinction risk under catastrophes than under diffusions. Together, these results provide insight into a wide range of stochastic dynamical systems important for ecology and conservation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Facilitating professional liaison in collaborative care for depression in UK primary care; a qualitative study utilising normalisation process theory.

    PubMed

    Coupe, Nia; Anderson, Emma; Gask, Linda; Sykes, Paul; Richards, David A; Chew-Graham, Carolyn

    2014-05-01

    Collaborative care (CC) is an organisational framework which facilitates the delivery of a mental health intervention to patients by case managers in collaboration with more senior health professionals (supervisors and GPs), and is effective for the management of depression in primary care. However, there remains limited evidence on how to successfully implement this collaborative approach in UK primary care. This study aimed to explore to what extent CC impacts on professional working relationships, and if CC for depression could be implemented as routine in the primary care setting. This qualitative study explored perspectives of the 6 case managers (CMs), 5 supervisors (trial research team members) and 15 general practitioners (GPs) from practices participating in a randomised controlled trial of CC for depression. Interviews were transcribed verbatim and data was analysed using a two-step approach using an initial thematic analysis, and a secondary analysis using the Normalisation Process Theory concepts of coherence, cognitive participation, collective action and reflexive monitoring with respect to the implementation of CC in primary care. Supervisors and CMs demonstrated coherence in their understanding of CC, and consequently reported good levels of cognitive participation and collective action regarding delivering and supervising the intervention. GPs interviewed showed limited understanding of the CC framework, and reported limited collaboration with CMs: barriers to collaboration were identified. All participants identified the potential or experienced benefits of a collaborative approach to depression management and were able to discuss ways in which collaboration can be facilitated. Primary care professionals in this study valued the potential for collaboration, but GPs' understanding of CC and organisational barriers hindered opportunities for communication. Further work is needed to address these organisational barriers in order to facilitate collaboration around individual patients with depression, including shared IT systems, facilitating opportunities for informal discussion and building in formal collaboration into the CC framework. ISRCTN32829227 30/9/2008.

  9. A Review of Anesthetic Effects on Renal Function: Potential Organ Protection.

    PubMed

    Motayagheni, Negar; Phan, Sheshanna; Eshraghi, Crystal; Nozari, Ala; Atala, Anthony

    2017-01-01

    Renal protection is a critical concept for anesthesiologists, nephrologists, and urologists, since anesthesia and renal function are highly interconnected and can potentially interfere with one another. Therefore, a comprehensive understanding of anesthetic drugs and their effects on renal function remains fundamental to the success of renal surgeries, especially transplant procedures. Some experimental studies have shown that some anesthetics provide protection against renal ischemia/reperfusion (IR) injury, but there is limited clinical evidence. The effects of anesthetic drugs on renal failure are particularly important in the context of kidney transplantation, since the conditions of preservation following removal profoundly influence the recovery of organ function. Currently, preservation procedures are typically based on the usage of a cold-storage solution. Some anesthetic drugs induce anti-inflammatory, anti-necrotic, and anti-apoptotic effects. A more thorough understanding of anesthetic effects on renal function can present a novel approach for developing organ-protective strategies. The aim of this review is to discuss the effects of different anesthetic drugs on renal function, with particular focus on IR injury. Many studies have demonstrated the organ-protective effects of some anesthetic drugs, specifically propofol, which indicate the potential of some anesthetics to introduce novel organ protective targets. This is not surprising, since lipid emulsions are major components of propofol, which accumulating data show provide organ protective effects against IR injury. Key Messages: Thorough understanding of the interaction between anesthetic drugs and renal function remains fundamental to the delivery of safe perioperative care and to optimizing outcomes after renal surgeries, particularly transplant procedures. Anesthetics can be repurposed for organ protection with more information about their effects, especially during transplant procedures. Here, we review the effects of different anesthetic drugs - specifically those that contain lipids in their structure, with special reference to IR injury. © 2017 S. Karger AG, Basel.

  10. Disability Transitions and Health Expectancies among Adults 45 Years and Older in Malawi: A Cohort-Based Model

    PubMed Central

    Payne, Collin F.; Mkandawire, James; Kohler, Hans-Peter

    2013-01-01

    Background Falling fertility and increasing life expectancy contribute to a growing elderly population in sub-Saharan Africa (SSA); by 2060, persons aged 45 y and older are projected to be 25% of SSA's population, up from 10% in 2010. Aging in SSA is associated with unique challenges because of poverty and inadequate social supports. However, despite its importance for understanding the consequences of population aging, the evidence about the prevalence of disabilities and functional limitations due to poor physical health among older adults in SSA continues to be very limited. Methods and Findings Participants came from 2006, 2008, and 2010 waves of the Malawi Longitudinal Survey of Families and Health, a study of the rural population in Malawi. We investigate how poor physical health results in functional limitations that limit the day-to-day activities of individuals in domains relevant to this subsistence-agriculture context. These disabilities were parameterized based on questions from the SF-12 questionnaire about limitations in daily living activities. We estimated age-specific patterns of functional limitations and the transitions over time between different disability states using a discrete-time hazard model. The estimated transition rates were then used to calculate the first (to our knowledge) microdata-based health expectancies calculated for SSA. The risks of experiencing functional limitations due to poor physical health are high in this population, and the onset of disabilities happens early in life. Our analyses show that 45-y-old women can expect to spend 58% (95% CI, 55%–64%) of their remaining 28 y of life (95% CI, 25.7–33.5) with functional limitations; 45-y-old men can expect to live 41% (95% CI, 35%–46%) of their remaining 25.4 y (95% CI, 23.3–28.8) with such limitations. Disabilities related to functional limitations are shown to have a substantial negative effect on individuals' labor activities, and are negatively related to subjective well-being. Conclusions Individuals in this population experience a lengthy struggle with disabling conditions in adulthood, with high probabilities of remitting and relapsing between states of functional limitation. Given the strong association of disabilities with work efforts and subjective well-being, this research suggests that current national health policies and international donor-funded health programs in SSA inadequately target the physical health of mature and older adults. Please see later in the article for the Editors' Summary PMID:23667343

  11. Particle Engineering of Excipients for Direct Compression: Understanding the Role of Material Properties.

    PubMed

    Mangal, Sharad; Meiser, Felix; Morton, David; Larson, Ian

    2015-01-01

    Tablets represent the preferred and most commonly dispensed pharmaceutical dosage form for administering active pharmaceutical ingredients (APIs). Minimizing the cost of goods and improving manufacturing output efficiency has motivated companies to use direct compression as a preferred method of tablet manufacturing. Excipients dictate the success of direct compression, notably by optimizing powder formulation compactability and flow, thus there has been a surge in creating excipients specifically designed to meet these needs for direct compression. Greater scientific understanding of tablet manufacturing coupled with effective application of the principles of material science and particle engineering has resulted in a number of improved direct compression excipients. Despite this, significant practical disadvantages of direct compression remain relative to granulation, and this is partly due to the limitations of direct compression excipients. For instance, in formulating high-dose APIs, a much higher level of excipient is required relative to wet or dry granulation and so tablets are much bigger. Creating excipients to enable direct compression of high-dose APIs requires the knowledge of the relationship between fundamental material properties and excipient functionalities. In this paper, we review the current understanding of the relationship between fundamental material properties and excipient functionality for direct compression.

  12. Leaky nitrogen cycle in pristine African montane rainforest soil

    NASA Astrophysics Data System (ADS)

    Rütting, Tobias; Cizungu Ntaboba, Landry; Roobroeck, Dries; Bauters, Marijn; Huygens, Dries; Boeckx, Pascal

    2015-10-01

    Many pristine humid tropical forests show simultaneously high nitrogen (N) richness and sustained loss of bioavailable N forms. To better understand this apparent upregulation of the N cycle in tropical forests, process-based understanding of soil N transformations, in geographically diverse locations, remains paramount. Field-based evidence is limited and entirely lacking for humid tropical forests on the African continent. This study aimed at filling both knowledge gaps by monitoring N losses and by conducting an in situ 15N labeling experiment in the Nyungwe tropical montane forest in Rwanda. Here we show that this tropical forest shows high nitrate (NO3-) leaching losses, confirming findings from other parts of the world. Gross N transformation rates point to an open soil N cycle with mineralized N nitrified rather than retained via immobilization; gross immobilization of NH4+ and NO3- combined accounted for 37% of gross mineralization, and plant N uptake is dominated by ammonium (NH4+). This study provided new process understanding of soil N cycling in humid tropical forests and added geographically independent evidence that humid tropical forests are characterized by soil N dynamics and N inputs sustaining bioavailable N loss.

  13. Unspoken phenomena: using the photovoice method to enrich phenomenological inquiry.

    PubMed

    Plunkett, Robyn; Leipert, Beverly D; Ray, Susan L

    2013-06-01

    Photovoice is a powerful method that is gaining momentum in nursing research. As a relatively new method in nursing science, the situatedness of photovoice within or alongside various research methodologies in a single study remains in a stage of early development. The purpose of this paper is to discuss the photovoice method as a means to elicit phenomenological data when researching the lived experience. While the foundational bases of phenomenology and photovoice differ substantially, the argument presented in this paper suggests that the photovoice method can be successfully used in phenomenological inquiry provided that significant rigour checks are pursued. This includes reflecting upon the origins and understandings of both methodology and method to promote methodological congruency. Data collection and analysis approaches that contribute to phenomenological inquiry using the photovoice method in addition to rigour and ethical considerations are discussed. The use of data generated from photovoice in phenomenological inquiry may fill a void of understanding furnished by limitations of traditional phenomenological inquiry and of spoken language and can enhance understanding of the lived experience, which may not always be best understood by words alone. © 2012 John Wiley & Sons Ltd.

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

    PubMed

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

    2017-01-01

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

  15. Piecing together the fragments: Elucidating edge effects on forest carbon dynamics

    NASA Astrophysics Data System (ADS)

    Hutyra, L.; Smith, I. A.; Reinmann, A.; Marrs, J.; Thompson, J.

    2017-12-01

    Forest fragmentation is pervasive throughout the world's forests, impacting growing conditions and carbon dynamics through edge effects that produce gradients in microclimate, biogeochemistry, and stand structure. Despite the majority of the world's forests being <1km from an edge, our understanding of forest carbon dynamics is largely derived from intact forest systems. In the northeastern USA, we find that over 23% of the current forest area is just 30m from an agricultural or developed edge. Edge effects on the carbon cycle vary in their magnitude by biome, but current forest carbon accounting methods and ecosystem models largely do not include edge effects, highlighting an important gap in our understanding of the terrestrial carbon cycle. Characterizing the role of forest fragmentation in regional and global biogeochemical cycles necessitates advancing our understanding of how shifts in microenvironment at the forest edge interact with local prevailing drivers of global change and limitations to microbial activity and forest growth. This study synthesizes the literature related to edge effects and the carbon cycle, considering how fragmentation affects the growing conditions of the world's remaining forests based on risks and opportunities for forests near the edge.

  16. Improvement of Human Keratinocyte Migration by a Redox Active Bioelectric Dressing

    PubMed Central

    Banerjee, Jaideep; Das Ghatak, Piya; Roy, Sashwati; Khanna, Savita; Sequin, Emily K.; Bellman, Karen; Dickinson, Bryan C.; Suri, Prerna; Subramaniam, Vish V.; Chang, Christopher J.; Sen, Chandan K.

    2014-01-01

    Exogenous application of an electric field can direct cell migration and improve wound healing; however clinical application of the therapy remains elusive due to lack of a suitable device and hence, limitations in understanding the molecular mechanisms. Here we report on a novel FDA approved redox-active Ag/Zn bioelectric dressing (BED) which generates electric fields. To develop a mechanistic understanding of how the BED may potentially influence wound re-epithelialization, we direct emphasis on understanding the influence of BED on human keratinocyte cell migration. Mapping of the electrical field generated by BED led to the observation that BED increases keratinocyte migration by three mechanisms: (i) generating hydrogen peroxide, known to be a potent driver of redox signaling, (ii) phosphorylation of redox-sensitive IGF1R directly implicated in cell migration, and (iii) reduction of protein thiols and increase in integrinαv expression, both of which are known to be drivers of cell migration. BED also increased keratinocyte mitochondrial membrane potential consistent with its ability to fuel an energy demanding migration process. Electric fields generated by a Ag/Zn BED can cross-talk with keratinocytes via redox-dependent processes improving keratinocyte migration, a critical event in wound re-epithelialization. PMID:24595050

  17. Identifying sources of acidity and spatial distribution of acid sulfate soils in the Anglesea River catchment, southern Australia

    NASA Astrophysics Data System (ADS)

    Wong, Vanessa; Yau, Chin; Kennedy, David

    2015-04-01

    Globally, coastal and estuarine floodplains are frequently underlain by sulfidic sediments. When exposed to oxygen, sulfidic sediments oxidise to form acid sulfate soils, adversely impacting on floodplain health and adjacent aquatic ecoystems. In eastern Australia, our understanding of the formation of these coastal and estuarine floodplains, and hence, spatial distribution of acid sulfate soils, is relatively well established. These soils have largely formed as a result of sedimentation of coastal river valleys approximately 6000 years BP when sea levels were one to two metres higher. However, our understanding of the evolution of estuarine systems and acid sulfate soil formation, and hence, distribution, in southern Australia remains limited. The Anglesea River, in southern Australia, is subjected to frequent episodes of poor water quality and low pH resulting in closure of the river and, in extreme cases, large fish kill events. This region is heavily reliant on tourism and host to a number of iconic features, including the Great Ocean Road and Twelve Apostles. Poor water quality has been linked to acid leakage from mining activities and Tertiary-aged coal seams, peat swamps and acid sulfate soils in the region. However, our understanding of the sources of acidity and distribution of acid sulfate soils in this region remains poor. In this study, four sites on the Anglesea River floodplain were sampled, representative of the main vegetation communities. Peat swamps and intertidal marshes were both significant sources of acidity on the floodplain in the lower catchment. However, acid neutralising capacity provided by carbonate sands suggests that there are additional sources of acidity higher in the catchment. This pilot study has highlighted the complexity in the links between the floodplain, upper catchment and waterways with further research required to understand these links for targeted acid management strategies.

  18. Positive feedback in the transition from sexual reproduction to parthenogenesis

    PubMed Central

    Schwander, Tanja; Vuilleumier, Séverine; Dubman, Janie; Crespi, Bernard J.

    2010-01-01

    Understanding how new phenotypes evolve is challenging because intermediate stages in transitions from ancestral to derived phenotypes often remain elusive. Here we describe and evaluate a new mechanism facilitating the transition from sexual reproduction to parthenogenesis. In many sexually reproducing species, a small proportion of unfertilized eggs can hatch spontaneously (‘tychoparthenogenesis’) and develop into females. Using an analytical model, we show that if females are mate-limited, tychoparthenogenesis can result in the loss of males through a positive feedback mechanism whereby tychoparthenogenesis generates female-biased sex ratios and increasing mate limitation. As a result, the strength of selection for tychoparthenogenesis increases in concert with the proportion of tychoparthenogenetic offspring in the sexual population. We then tested the hypothesis that mate limitation selects for tychoparthenogenesis and generates female-biased sex ratios, using data from natural populations of sexually reproducing Timema stick insects. Across 41 populations, both the tychoparthenogenesis rates and the proportions of females increased exponentially as the density of individuals decreased, consistent with the idea that low densities of individuals result in mate limitation and selection for reproductive insurance through tychoparthenogenesis. Our model and data from Timema populations provide evidence for a simple mechanism through which parthenogenesis can evolve rapidly in a sexual population. PMID:20071382

  19. Does greater thermal plasticity facilitate range expansion of an invasive terrestrial anuran into higher latitudes?

    PubMed

    Winwood-Smith, Hugh S; Alton, Lesley A; Franklin, Craig E; White, Craig R

    2015-01-01

    Temperature has pervasive effects on physiological processes and is critical in setting species distribution limits. Since invading Australia, cane toads have spread rapidly across low latitudes, but slowly into higher latitudes. Low temperature is the likely factor limiting high-latitude advancement. Several previous attempts have been made to predict future cane toad distributions in Australia, but understanding the potential contribution of phenotypic plasticity and adaptation to future range expansion remains challenging. Previous research demonstrates the considerable thermal metabolic plasticity of the cane toad, but suggests limited thermal plasticity of locomotor performance. Additionally, the oxygen-limited thermal tolerance hypothesis predicts that reduced aerobic scope sets thermal limits for ectotherm performance. Metabolic plasticity, locomotor performance and aerobic scope are therefore predicted targets of natural selection as cane toads invade colder regions. We measured these traits at temperatures of 10, 15, 22.5 and 30°C in low- and high-latitude toads acclimated to 15 and 30°C, to test the hypothesis that cane toads have adapted to cooler temperatures. High-latitude toads show increased metabolic plasticity and higher resting metabolic rates at lower temperatures. Burst locomotor performance was worse for high-latitude toads. Other traits showed no regional differences. We conclude that increased metabolic plasticity may facilitate invasion into higher latitudes by maintaining critical physiological functions at lower temperatures.

  20. Health literacy and communication quality in health care organizations.

    PubMed

    Wynia, Matthew K; Osborn, Chandra Y

    2010-01-01

    The relationship between limited health literacy and poor health may be due, in part, to poor communication quality within health care delivery organizations. We explored the relationship between health literacy status and receiving patient-centered communication in clinics and hospitals serving communication-vulnerable patient populations. Thirteen health care organizations nationwide distributed a survey to 5929 patients. All patients completed seven items assessing patient-centered communication. One third also completed three items assessing health literacy. The majority of patients had self-reported health literacy challenges, reporting problems learning about their medical condition because of difficulty understanding written information (53%), a lack of confidence in completing medical forms by themselves (61%), and needing someone to help them read hospital/clinic materials (57%). Logistic regression models showed that, after adjustment for patient demographic characteristics and health care organization type, patients with limited health literacy were 28% to 79% less likely than those with adequate health literacy to report their health care organization "always" provides patient-centered communication across seven communication items. Using a scaled composite of these items, limited health literacy remained associated with lower reported communication quality. These results suggest that improving communication quality in health care organizations might help to address the challenges facing patients with limited health literacy. They also highlight that efforts to address the needs of patients with limited health literacy should be sensitive to the range of communication challenges confronting these patients and their caregivers.

  1. Factors associated with the risk perception and purchase decisions of Fukushima-related food in South Korea

    PubMed Central

    Song, Min Kyoung; Lee, Hyang Ki; Park, Sunhoo; Jin, Young Woo

    2017-01-01

    Following the Fukushima nuclear power plant accident, the risk level perceived by Koreans on the radioactive contamination of Japanese food that is being distributed in Korea remains high. Many of these perceptions are based on subjective risk perception rather than an objective measure with scientific evidence, which makes communicating risks more difficult; therefore, it is critical to understand factors associated with risk perception for effective risk communication. In this study, we identified variables that are associated with buying tendencies and opinions about the regulatory policy of Japanese seafood after the accident. A survey was conducted with 1045 adults aged over 20 years in Korea. The majority (68.8%) responded that they would not purchase Japanese seafood when radioactivity levels in the food were non-detectable. Moreover, 82.2% responded that the current levels of import restrictions on Japanese seafood must be maintained. Despite many concerns regarding the exposure to radiation and the effects from food products following the Fukushima accident, the opportunities to encounter and to collect correct information remain limited and average radioactive knowledge scores were low (3.63 out of 9). Of the various characteristics associated with purchase decisions and agreement on the current import restraints of Japanese seafood, trust levels in the government and the mass media for providing information on radioactivity were major factors that influenced risk perception. While the scope of this study was limited to seafood, it is very closely tied to daily lives, where we revealed differences about risk perceptions and agreement on import restraints of Japanese seafood per a complex mixture of individual characteristics and the surrounding environment. These results provide useful information to understand the risk perception of the potential radioactive contamination of food and to predict the public’s responses to food consumption and import restraint policies due to nuclear accidents in neighboring countries. PMID:29117237

  2. Factors associated with the risk perception and purchase decisions of Fukushima-related food in South Korea.

    PubMed

    Lee, Dalnim; Seo, Songwon; Song, Min Kyoung; Lee, Hyang Ki; Park, Sunhoo; Jin, Young Woo

    2017-01-01

    Following the Fukushima nuclear power plant accident, the risk level perceived by Koreans on the radioactive contamination of Japanese food that is being distributed in Korea remains high. Many of these perceptions are based on subjective risk perception rather than an objective measure with scientific evidence, which makes communicating risks more difficult; therefore, it is critical to understand factors associated with risk perception for effective risk communication. In this study, we identified variables that are associated with buying tendencies and opinions about the regulatory policy of Japanese seafood after the accident. A survey was conducted with 1045 adults aged over 20 years in Korea. The majority (68.8%) responded that they would not purchase Japanese seafood when radioactivity levels in the food were non-detectable. Moreover, 82.2% responded that the current levels of import restrictions on Japanese seafood must be maintained. Despite many concerns regarding the exposure to radiation and the effects from food products following the Fukushima accident, the opportunities to encounter and to collect correct information remain limited and average radioactive knowledge scores were low (3.63 out of 9). Of the various characteristics associated with purchase decisions and agreement on the current import restraints of Japanese seafood, trust levels in the government and the mass media for providing information on radioactivity were major factors that influenced risk perception. While the scope of this study was limited to seafood, it is very closely tied to daily lives, where we revealed differences about risk perceptions and agreement on import restraints of Japanese seafood per a complex mixture of individual characteristics and the surrounding environment. These results provide useful information to understand the risk perception of the potential radioactive contamination of food and to predict the public's responses to food consumption and import restraint policies due to nuclear accidents in neighboring countries.

  3. Hypothermia translocates nitric oxide synthase from cytosol to membrane in snail neurons.

    PubMed

    Rószer, Tamás; Kiss-Tóth, Eva; Rózsa, Dávid; Józsa, Tamás; Szentmiklósi, A József; Bánfalvi, Gáspár

    2010-11-01

    Neuronal nitric oxide (NO) levels are modulated through the control of catalytic activity of NO synthase (NOS). Although signals limiting excess NO synthesis are being extensively studied in the vertebrate nervous system, our knowledge is rather limited on the control of NOS in neurons of invertebrates. We have previously reported a transient inactivation of NOS in hibernating snails. In the present study, we aimed to understand the mechanism leading to blocked NO production during hypothermic periods of Helix pomatia. We have found that hypothermic challenge translocated NOS from the cytosol to the perinuclear endoplasmic reticulum, and that this cytosol to membrane trafficking was essential for inhibition of NO synthesis. Cold stress also downregulated NOS mRNA levels in snail neurons, although the amount of NOS protein remained unaffected in response to hypothermia. Our studies with cultured neurons and glia cells revealed that glia-neuron signaling may inhibit membrane binding and inactivation of NOS. We provide evidence that hypothermia keeps NO synthesis "hibernated" through subcellular redistribution of NOS.

  4. Nitrogen dynamics in managed boreal forests: Recent advances and future research directions.

    PubMed

    Sponseller, Ryan A; Gundale, Michael J; Futter, Martyn; Ring, Eva; Nordin, Annika; Näsholm, Torgny; Laudon, Hjalmar

    2016-02-01

    Nitrogen (N) availability plays multiple roles in the boreal landscape, as a limiting nutrient to forest growth, determinant of terrestrial biodiversity, and agent of eutrophication in aquatic ecosystems. We review existing research on forest N dynamics in northern landscapes and address the effects of management and environmental change on internal cycling and export. Current research foci include resolving the nutritional importance of different N forms to trees and establishing how tree-mycorrhizal relationships influence N limitation. In addition, understanding how forest responses to external N inputs are mediated by above- and belowground ecosystem compartments remains an important challenge. Finally, forestry generates a mosaic of successional patches in managed forest landscapes, with differing levels of N input, biological demand, and hydrological loss. The balance among these processes influences the temporal patterns of stream water chemistry and the long-term viability of forest growth. Ultimately, managing forests to keep pace with increasing demands for biomass production, while minimizing environmental degradation, will require multi-scale and interdisciplinary perspectives on landscape N dynamics.

  5. Ecosystem services: From theory to implementation

    PubMed Central

    Daily, Gretchen C.; Matson, Pamela A.

    2008-01-01

    Around the world, leaders are increasingly recognizing ecosystems as natural capital assets that supply life-support services of tremendous value. The challenge is to turn this recognition into incentives and institutions that will guide wise investments in natural capital, on a large scale. Advances are required on three key fronts, each featured here: the science of ecosystem production functions and service mapping; the design of appropriate finance, policy, and governance systems; and the art of implementing these in diverse biophysical and social contexts. Scientific understanding of ecosystem production functions is improving rapidly but remains a limiting factor in incorporating natural capital into decisions, via systems of national accounting and other mechanisms. Novel institutional structures are being established for a broad array of services and places, creating a need and opportunity for systematic assessment of their scope and limitations. Finally, it is clear that formal sharing of experience, and defining of priorities for future work, could greatly accelerate the rate of innovation and uptake of new approaches. PMID:18621697

  6. Effect of subsidies to fossil fuel companies on United States crude oil production

    NASA Astrophysics Data System (ADS)

    Erickson, Peter; Down, Adrian; Lazarus, Michael; Koplow, Doug

    2017-11-01

    Countries in the G20 have committed to phase out `inefficient' fossil fuel subsidies. However, there remains a limited understanding of how subsidy removal would affect fossil fuel investment returns and production, particularly for subsidies to producers. Here, we assess the impact of major federal and state subsidies on US crude oil producers. We find that, at recent oil prices of US50 per barrel, tax preferences and other subsidies push nearly half of new, yet-to-be-developed oil investments into profitability, potentially increasing US oil production by 17 billion barrels over the next few decades. This oil, equivalent to 6 billion tonnes of CO2, could make up as much as 20% of US oil production through 2050 under a carbon budget aimed at limiting warming to 2 °C. Our findings show that removal of tax incentives and other fossil fuel support policies could both fulfil G20 commitments and yield climate benefits.

  7. Wall roughness induces asymptotic ultimate turbulence

    NASA Astrophysics Data System (ADS)

    Zhu, Xiaojue; Verschoof, Ruben A.; Bakhuis, Dennis; Huisman, Sander G.; Verzicco, Roberto; Sun, Chao; Lohse, Detlef

    2018-04-01

    Turbulence governs the transport of heat, mass and momentum on multiple scales. In real-world applications, wall-bounded turbulence typically involves surfaces that are rough; however, characterizing and understanding the effects of wall roughness on turbulence remains a challenge. Here, by combining extensive experiments and numerical simulations, we examine the paradigmatic Taylor-Couette system, which describes the closed flow between two independently rotating coaxial cylinders. We show how wall roughness greatly enhances the overall transport properties and the corresponding scaling exponents associated with wall-bounded turbulence. We reveal that if only one of the walls is rough, the bulk velocity is slaved to the rough side, due to the much stronger coupling to that wall by the detaching flow structures. If both walls are rough, the viscosity dependence is eliminated, giving rise to asymptotic ultimate turbulence—the upper limit of transport—the existence of which was predicted more than 50 years ago. In this limit, the scaling laws can be extrapolated to arbitrarily large Reynolds numbers.

  8. DMDs for multi-object near-infrared spectrographs in astronomy

    NASA Astrophysics Data System (ADS)

    Smee, Stephen A.; Barkhouser, Robert; Hope, Stephen; Conley, Devin; Gray, Aidan; Hope, Gavin; Robberto, Massimo

    2018-02-01

    The Digital Micromirror Device (DMD), typically used in projection screen technology, has utility in instrumentation for astronomy as a digitally programmable slit in a spectrograph. When placed at an imaging focal plane the device can be used to selectively direct light from astronomical targets into the optical path of a spectrograph, while at the same time directing the remaining light into an imaging camera, which can be used for slit alignment, science imaging, or both. To date the use of DMDs in astronomy has been limited, especially for instruments that operate in the near infrared (1 - 2.5 μm). This limitation is due in part to a host of technical challenges with respect to DMDs that, to date, have not been thoroughly explored. Those challenges include operation at cryogenic temperature, control electronics that facilitate DMD use at these temperatures, window coatings properly coated for the near infrared bandpass, and scattered light. This paper discusses these technical challenges and presents progress towards understanding and mitigating them.

  9. A novel role of cytosolic protein synthesis inhibition in aminoglycoside ototoxicity

    PubMed Central

    Francis, Shimon P.; Katz, Joshua; Fanning, Kathryn D.; Harris, Kimberly A.; Nicholas, Brian D.; Lacy, Michael; Pagana, James; Agris, Paul F.; Shin, Jung-Bum

    2013-01-01

    Ototoxicity is a main dose-limiting factor in the clinical application of aminoglycoside antibiotics. Despite longstanding research efforts, our understanding of the mechanisms underlying aminoglycoside ototoxicity remains limited. Here we report the discovery of a novel stress pathway that contributes to aminoglycoside-induced hair cell degeneration. Modifying the recently developed bioorthogonal noncanonical amino acid tagging (BONCAT) method, we used click-chemistry to study the role of protein synthesis activity in aminoglycoside-induced hair cell stress. We demonstrate that aminoglycosides inhibit protein synthesis in hair cells and activate a signaling pathway similar to ribotoxic stress response, contributing to hair cell degeneration. The ability of a particular aminoglycoside to inhibit protein synthesis and to activate the c-Jun N-terminal kinase (JNK) pathway correlated well with its ototoxic potential. Finally, we report that a FDA-approved drug known to inhibit ribotoxic stress response also prevents JNK activation and improves hair cell survival, opening up novel strategies to prevent and treat aminoglycoside ototoxicity. PMID:23407963

  10. Barriers to Access and Adoption of Pre-Exposure Prophylaxis for the Prevention of HIV Among Men Who Have Sex With Men (MSM) in a Relatively Rural State.

    PubMed

    Hubach, Randolph D; Currin, Joseph M; Sanders, Carissa A; Durham, André R; Kavanaugh, Katherine E; Wheeler, Denna L; Croff, Julie M

    2017-08-01

    Biomedical intervention approaches, including antiretroviral pre-exposure prophylaxis (PrEP), have been demonstrated to reduce HIV incidence among several at-risk populations and to be cost effective. However, there is limited understanding of PrEP access and uptake among men who have sex with men (MSM) residing in relatively rural states. Twenty semistructured interviews were conducted (August-November 2016) to assess opinions of and perceived barriers to accessing and adopting PrEP among MSM residing in Oklahoma. Participants perceived substantial barriers to accessing PrEP including a stigmatizing environment and less access to quality, LGBT-sensitive medical care. Overall, geographic isolation limits access to health providers and resources that support sexual health for Oklahoma MSM. Addressing stigma situated across ecological levels in an effort to increase adoption of PrEP by MSM residing in rural states remains necessary. Without this, social determinants may continue to negatively influence PrEP adoption and sexual health outcomes.

  11. Scleroderma: nomenclature, etiology, pathogenesis, prognosis, and treatments: facts and controversies.

    PubMed

    Fett, Nicole

    2013-01-01

    Scleroderma refers to a heterogeneous group of autoimmune fibrosing disorders. The nomenclature of scleroderma has changed dramatically in recent years, with morphea (localized scleroderma), limited cutaneous systemic sclerosis, diffuse cutaneous systemic sclerosis, and systemic sclerosis sine scleroderma encompassing the currently accepted disease subtypes. Major advances have been made in the molecular studies of morphea and systemic sclerosis; however, their etiologies and pathogenesis remain incompletely understood. Although morphea and systemic sclerosis demonstrate activation of similar inflammatory and fibrotic pathways, important differences in signaling pathways and gene signatures indicate they are likely biologically distinct processes. Morphea can cause significant morbidity but does not affect mortality, whereas systemic sclerosis has the highest disease-specific mortality of all autoimmune connective tissue diseases. Treatment recommendations for morphea and systemic sclerosis are based on limited data and largely expert opinions. Current collaborative efforts in morphea and systemic sclerosis research will hopefully lead to better understanding of the etiology and pathogenesis of these rare and varied diseases and improved treatment options. Published by Elsevier Inc.

  12. Preliminary Recommendations for the Collection, Storage, and Analysis of UAS Safety Data

    NASA Technical Reports Server (NTRS)

    Enomoto, Francis; Bushnell, David; Denney, Ewen; Pai, Ganesh; Schumann, Johann

    2013-01-01

    Although the use of UASs in military and public service operations is proliferating, civilian use of UASs remains limited in the United States today. With efforts underway to accommodate and integrate UASs into the NAS, a proactive understanding of safety issues, i.e., the unique hazards and the corresponding risks that UASs pose not only through their operations for commercial purposes, but also to existing operations in the NAS, is especially important so as to (a) support the development of a sound regulatory basis, (b) regulate, design and properly equip UASs, and (c) effectively mitigate the risks posed. Data, especially about system and component failures, incidents, and accidents, provides valuable insight into how performance and operational capabilities/limitations contribute to hazards. Since the majority of UAS operations today take place in a context that is significantly different from the norm in civil aviation, i.e., with different operational goals and standards, identifying that which constitutes useful and sufficient data on UASs and their operations is a substantial research challenge.

  13. Ecosystem services: from theory to implementation.

    PubMed

    Daily, Gretchen C; Matson, Pamela A

    2008-07-15

    Around the world, leaders are increasingly recognizing ecosystems as natural capital assets that supply life-support services of tremendous value. The challenge is to turn this recognition into incentives and institutions that will guide wise investments in natural capital, on a large scale. Advances are required on three key fronts, each featured here: the science of ecosystem production functions and service mapping; the design of appropriate finance, policy, and governance systems; and the art of implementing these in diverse biophysical and social contexts. Scientific understanding of ecosystem production functions is improving rapidly but remains a limiting factor in incorporating natural capital into decisions, via systems of national accounting and other mechanisms. Novel institutional structures are being established for a broad array of services and places, creating a need and opportunity for systematic assessment of their scope and limitations. Finally, it is clear that formal sharing of experience, and defining of priorities for future work, could greatly accelerate the rate of innovation and uptake of new approaches.

  14. Challenges Facing Crop Production And (Some) Potential Solutions

    NASA Astrophysics Data System (ADS)

    Schnable, P. S.

    2017-12-01

    To overcome some of the myriad challenges facing sustainable crop production we are seeking to develop statistical models that will predict crop performance in diverse agronomic environments. Crop phenotypes such as yield and drought tolerance are controlled by genotype, environment (considered broadly) and their interaction (GxE). As a consequence of the next generation sequencing revolution genotyping data are now available for a wide diversity of accessions in each of the major crops. The necessary volumes of phenotypic data, however, remain limiting and our understanding of molecular basis of GxE is minimal. To address this limitation, we are collaborating with engineers to construct new sensors and robots to automatically collect large volumes of phenotypic data. Two types of high-throughput, high-resolution, field-based phenotyping systems and new sensors will be described. Some of these technologies will be introduced within the context of the Genomes to Fields Initiative. Progress towards developing predictive models will be briefly summarized. An administrative structure that fosters transdisciplinary collaborations will be briefly described.

  15. Permissive hypofiltration

    PubMed Central

    2012-01-01

    Acute kidney injury (AKI) is a syndrome with a multitude of causes and is associated with high mortality and a permanent loss of renal function. Our current understanding of the most common causes of AKI is limited, and thus a silver bullet therapy remains elusive. A change in the approach to AKI that shifts away from the primary composite endpoint of death/dialysis, and instead focuses on improving survival and mitigating permanent renal damage, is likely to be more fruitful. We suggest that the current approach of augmenting renal function by increasing the renal blood flow or glomerular filtration rate during AKI may actually worsen outcomes. Analogous to the approach towards adult respiratory distress syndrome that limits ventilator-induced lung injury, we propose the concept of permissive hypofiltration. The primary goals of this approach are: resting the kidney by providing early renal replacement therapy, avoiding the potentially injurious adverse events that occur during AKI (for example, fluid overload, hypophosphatemia, hypothermia, and so forth), and initiating therapies focused on improving survival and mitigating permanent loss of kidney function. PMID:22839207

  16. SPED light sheet microscopy: fast mapping of biological system structure and function

    PubMed Central

    Tomer, Raju; Lovett-Barron, Matthew; Kauvar, Isaac; Andalman, Aaron; Burns, Vanessa M.; Sankaran, Sethuraman; Grosenick, Logan; Broxton, Michael; Yang, Samuel; Deisseroth, Karl

    2016-01-01

    The goal of understanding living nervous systems has driven interest in high-speed and large field-of-view volumetric imaging at cellular resolution. Light-sheet microscopy approaches have emerged for cellular-resolution functional brain imaging in small organisms such as larval zebrafish, but remain fundamentally limited in speed. Here we have developed SPED light sheet microscopy, which combines large volumetric field-of-view via an extended depth of field with the optical sectioning of light sheet microscopy, thereby eliminating the need to physically scan detection objectives for volumetric imaging. SPED enables scanning of thousands of volumes-per-second, limited only by camera acquisition rate, through the harnessing of optical mechanisms that normally result in unwanted spherical aberrations. We demonstrate capabilities of SPED microscopy by performing fast sub-cellular resolution imaging of CLARITY mouse brains and cellular-resolution volumetric Ca2+ imaging of entire zebrafish nervous systems. Together, SPED light sheet methods enable high-speed cellular-resolution volumetric mapping of biological system structure and function. PMID:26687363

  17. Calculus Limits Involving Infinity: The Role of Students' Informal Dynamic Reasoning

    ERIC Educational Resources Information Center

    Jones, Steven R.

    2015-01-01

    Few studies on calculus limits have centred their focus on student understanding of limits at infinity or infinite limits that involve continuous functions (as opposed to discrete sequences). This study examines student understanding of these types of limits using both pure mathematics and applied-science functions and formulas. Seven calculus…

  18. Using larval fish community structure to guide long-term monitoring of fish spawning activity

    USGS Publications Warehouse

    Pritt, Jeremy J.; Roseman, Edward F.; Ross, Jason E.; DeBruyne, Robin L.

    2015-01-01

    Larval fishes provide a direct indication of spawning activity and may therefore be useful for long-term monitoring efforts in relation to spawning habitat restoration. However, larval fish sampling can be time intensive and costly. We sought to understand the spatial and temporal structure of larval fish communities in the St. Clair–Detroit River system, Michigan–Ontario, to determine whether targeted larval fish sampling can be made more efficient for long-term monitoring. We found that larval fish communities were highly nested, with lower river segments and late-spring samples containing the highest genus richness of larval fish. We created four sampling scenarios for each river system: (1) using all available data, (2) limiting temporal sampling to late spring, (3) limiting spatial sampling to lower river segments only, and (4) limiting both spatial and temporal sampling. By limiting the spatial extent of sampling to lower river sites and/or limiting the temporal extent to the late-spring period, we found that effort could be reduced by more than 50% while maintaining over 75% of the observed and estimated total genus richness. Similarly, limiting the sampling effort to lower river sites and/or the late-spring period maintained between 65% and 93% of the observed richness of lithophilic-spawning genera and invasive genera. In general, community composition remained consistent among sampling scenarios. Targeted sampling offers a lower-cost alternative to exhaustive spatial and temporal sampling and may be more readily incorporated into long-term monitoring.

  19. Progress in improving provincial plans for nutrition through targeted technical assistance and local advocacy in Vietnam

    PubMed Central

    Harris, Jody; Nguyen, Phuong H.; To, Quyen; Frongillo, Edward A.; Menon, Purnima

    2016-01-01

    Vietnam has been decentralizing nutrition planning to provinces, which could help with local relevance and accountability. Assessment in 2009 found a continuing top-down approach, limited human capacity, and difficulty in integrating multiple sectors. Alive and Thrive (A&T) provided targeted assistance and capacity-building for 15 provincial plans for nutrition (PPNs). We aimed to (i) assess PPN content and quality improvements 2009–2014, and (ii) explain processes through which change occurred. Data consisted of interview-based assessments of provincial planning processes, annual PPN assessments, and tracking of A&T involvement. At endline, some provinces produced higher quality plans. Local planning skills improved, but capacity remained insufficient. Awareness of and support for nutrition improved, but some policy and legal environments were contradictory. Objectives were clearer, but use of data for planning remained inconsistent. Provinces became more proactive and creative, but remained constrained by slow approval processes and insufficient funding. Targeted assistance and local advocacy can improve decentralized planning, with success dependent on policy and programming contexts and ability to overcome constraints around capacity, investment, data use and remnants of centralized planning. We recommend strong engagement with planners at the national level to understand how to unblock major constraints; solutions must take into consideration the particular political, financial and administrative context. PMID:27198978

  20. Paleobiology and comparative morphology of a late Neandertal sample from El Sidron, Asturias, Spain.

    PubMed

    Rosas, Antonio; Martínez-Maza, Cayetana; Bastir, Markus; García-Tabernero, Antonio; Lalueza-Fox, Carles; Huguet, Rosa; Ortiz, José Eugenio; Julià, Ramón; Soler, Vicente; de Torres, Trinidad; Martínez, Enrique; Cañaveras, Juan Carlos; Sánchez-Moral, Sergio; Cuezva, Soledad; Lario, Javier; Santamaría, David; de la Rasilla, Marco; Fortea, Javier

    2006-12-19

    Fossil evidence from the Iberian Peninsula is essential for understanding Neandertal evolution and history. Since 2000, a new sample approximately 43,000 years old has been systematically recovered at the El Sidrón cave site (Asturias, Spain). Human remains almost exclusively compose the bone assemblage. All of the skeletal parts are preserved, and there is a moderate occurrence of Middle Paleolithic stone tools. A minimum number of eight individuals are represented, and ancient mtDNA has been extracted from dental and osteological remains. Paleobiology of the El Sidrón archaic humans fits the pattern found in other Neandertal samples: a high incidence of dental hypoplasia and interproximal grooves, yet no traumatic lesions are present. Moreover, unambiguous evidence of human-induced modifications has been found on the human remains. Morphologically, the El Sidrón humans show a large number of Neandertal lineage-derived features even though certain traits place the sample at the limits of Neandertal variation. Integrating the El Sidrón human mandibles into the larger Neandertal sample reveals a north-south geographic patterning, with southern Neandertals showing broader faces with increased lower facial heights. The large El Sidrón sample therefore augments the European evolutionary lineage fossil record and supports ecogeographical variability across Neandertal populations.

  1. On the centenary of Charcot: hysteria, suggestibility and hypnosis.

    PubMed

    Chertok, L

    1984-06-01

    In studying hysteria by means of hypnosis, Charcot placed emphasis on the psychological aetiology of the neuroses. Among his pupils, Freud alone grasped this epistemological turning-point, from which he made his great discoveries. But hysteria and hypnosis still remain today largely unknown. We have not yet elucidated the 'mysterious leap' between the psychological and the somatic for the former, and between the relational and the instrumental for the latter. While psychoanalysts have constantly concerned themselves with hysteria, they have shown a lack of interest in hypnosis after Freud abandoned its practice. According to Freud, thanks to transference, affect would be controlled by cognition, a viewpoint eminently suited to satisfy his rationalistic outlook. Affect, however, remains an unknown realm. The affective relationship has, at all events, acquired an ever-increasing importance in psychoanalysis during the last few years, with the emphasis on the early mother-child relationship. The 'affective locus' remains the basic, as well as the most obscure, element in the hypno-suggestive relationship. The behaviourist approach, which quantifies the 'vertical' dimension in depth, is a limited one. The study of the 'horizontal' dimension of subjective experience represents a new line of research, which may make it possible to distinguish different forms of hypnosis. The understanding of hypno-suggestion may throw light on psychoanalysis, psychotherapy, and the human sciences in general.

  2. MicroRNAs (miRNAs) as biomarker(s) for prognosis and diagnosis of gastrointestinal (GI) cancers.

    PubMed

    Macha, Muzafar A; Seshacharyulu, Parthasarathy; Krishn, Shiv Ram; Pai, Priya; Rachagani, Satyanarayana; Jain, Maneesh; Batra, Surinder K

    2014-01-01

    Gastrointestinal (GI) cancers remain one of the most common malignancies and are the second common cause of cancer deaths worldwide. The limited effectiveness of therapy for patients with advanced stage and recurrent disease is a reflection of an incomplete understanding of the molecular basis of GI carcinogenesis. Major advancements have improved our understanding of pathology and pathogenesis of GI cancers, but high mortality rates, unfavorable prognosis and lack of clinical predictive biomarkers provide an impetus to investigate new sensitive and specific diagnostic and prognostic markers for GI cancers. MicroRNAs (miRNAs) are short (19-24 nucleotides) noncoding RNA molecules that regulate gene expression at the posttranscriptional level thus playing an important role in modulating various biological processes including, but not limited to developmental processes, proliferation, apoptosis, metabolism, differentiation, epithelial-mechenchymal transition and are involved in the initiation and progression of various human cancers. Unique miRNA expression profiles have been observed in various cancer types at different stages, suggesting their potential as diagnostic and prognostic biomarkers. Due to their tumor-specific and tissue-specific expression profiles, stability, robust clinical assays for detection in serum as well as in formalin-fixed tissue samples, miRNAs have emerged as attractive candidates for diagnostic and prognostic applications. This review summarizes recent research supporting the utility of miRNAs as novel diagnostic and prognostic tools for GI cancers.

  3. MicroRNAs (miRNAs) as Biomarker(s) for Prognosis and Diagnosis of Gastrointestinal (GI) Cancers

    PubMed Central

    Macha, Muzafar A.; Seshacharyulu, Parthasarathy; Krishn, Shiv Ram; Pai, Priya; Rachagani, Satyanarayana; Jain, Maneesh; Batra, Surinder K.

    2014-01-01

    Gastrointestinal (GI) cancers remain one of the most common malignancies and are the second common cause of cancer deaths worldwide. The limited effectiveness of therapy for patients with advanced stage and recurrent disease is a reflection of an incomplete understanding of the molecular basis of GI carcinogenesis. Major advancements have improved our understanding of pathology and pathogenesis of GI cancers, but high mortality rates, unfavorable prognosis and lack of clinical predictive biomarkers provide an impetus to investigate new sensitive and specific diagnostic and prognostic markers for GI cancers. MicroRNAs (miRNAs) are short (19–24 nucleotides) noncoding RNA molecules that regulate gene expression at the posttranscriptional level thus playing an important role in modulating various biological processes including, but not limited, to developmental processes, proliferation, apoptosis, metabolism, differentiation, epithelial-mechenchymal transition and are involved in the initiation and progression of various human cancers. Unique miRNA expression profiles have been observed in various cancer types at different stages, suggesting their potential as diagnostic and prognostic biomarkers. Due to their tumor-specific and tissue-specific expression profiles, stability, robust clinical assays for detection in serum as well as in formalin-fixed tissue samples, miRNAs have emerged as attractive candidates for diagnostic and prognostic applications. This review summarizes recent research supporting the utility of miRNAs as novel diagnostic and prognostic tools for GI cancers. PMID:24479799

  4. Review and International Recommendation of Methods for Typing Neisseria gonorrhoeae Isolates and Their Implications for Improved Knowledge of Gonococcal Epidemiology, Treatment, and Biology

    PubMed Central

    Unemo, Magnus; Dillon, Jo-Anne R.

    2011-01-01

    Summary: Gonorrhea, which may become untreatable due to multiple resistance to available antibiotics, remains a public health problem worldwide. Precise methods for typing Neisseria gonorrhoeae, together with epidemiological information, are crucial for an enhanced understanding regarding issues involving epidemiology, test of cure and contact tracing, identifying core groups and risk behaviors, and recommending effective antimicrobial treatment, control, and preventive measures. This review evaluates methods for typing N. gonorrhoeae isolates and recommends various methods for different situations. Phenotypic typing methods, as well as some now-outdated DNA-based methods, have limited usefulness in differentiating between strains of N. gonorrhoeae. Genotypic methods based on DNA sequencing are preferred, and the selection of the appropriate genotypic method should be guided by its performance characteristics and whether short-term epidemiology (microepidemiology) or long-term and/or global epidemiology (macroepidemiology) matters are being investigated. Currently, for microepidemiological questions, the best methods for fast, objective, portable, highly discriminatory, reproducible, typeable, and high-throughput characterization are N. gonorrhoeae multiantigen sequence typing (NG-MAST) or full- or extended-length porB gene sequencing. However, pulsed-field gel electrophoresis (PFGE) and Opa typing can be valuable in specific situations, i.e., extreme microepidemiology, despite their limitations. For macroepidemiological studies and phylogenetic studies, DNA sequencing of chromosomal housekeeping genes, such as multilocus sequence typing (MLST), provides a more nuanced understanding. PMID:21734242

  5. Evaluating hillslope and riparian contributions to dissolved nitrogen (N) export from a boreal forest catchment

    NASA Astrophysics Data System (ADS)

    Blackburn, M.; Ledesma, José L. J.; Näsholm, Torgny; Laudon, Hjalmar; Sponseller, Ryan A.

    2017-02-01

    Catchment science has long held that the chemistry of small streams reflects the landscapes they drain. However, understanding the contribution of different landscape units to stream chemistry remains a challenge which frequently limits our understanding of export dynamics. For limiting nutrients such as nitrogen (N), an implicit assumption is that the most spatially extensive landscape units (e.g., uplands) act as the primary sources to surface waters, while near-stream zones function more often as sinks. These assumptions, based largely on studies in high-gradient systems or in regions with elevated inputs of anthropogenic N, may not apply to low-gradient, nutrient-poor, and peat-rich catchments characteristic of many northern ecosystems. We quantified patterns of N mobilization along a hillslope transect in a northern boreal catchment to assess the extent to which organic matter-rich riparian soils regulate the flux of N to streams. Contrary to the prevailing view of riparian functioning, we found that near-stream, organic soils supported concentrations and fluxes of ammonium (NH4+) and dissolved organic nitrogen that were much higher than the contributing upslope forest soils. These results suggest that stream N chemistry is connected to N mobilization and mineralization within the riparian zone rather than the wider landscape. Results further suggest that water table fluctuation in near-surface riparian soils may promote elevated rates of net N mineralization in these landscapes.

  6. Devil's Slide: An evolving feature of California's coastal landscape

    NASA Astrophysics Data System (ADS)

    Thomas, M.; Loague, K.

    2013-12-01

    Coastal landslides in the United States remain a persistent threat to human life and urban development. The focus of this study is a landslide-prone section of the central California coastline, approximately 20 km south of San Francisco, known as Devil's Slide. This investigation employs an extensive aerial image inventory, digital elevation models (DEMs), and a water balance / limit-equilibrium approach to better understand the spatial and temporal characteristics of deep-seated bedrock slides at the site. Photographic surveys of the area reveal nearly three kilometers of headscarp and a complex network of slope failures that respond to hydrologic, seismic, and anthropogenic perturbations. DEM analysis suggests that, for a 145-year period (1866 to 2010), the study area experienced an average coastal retreat rate of 0.14 m yr-1 and an average volumetric loss of 11,216 m3 yr-1. At least 38% of the landscape evolution in the steep coastal terrain has been driven by slope failure events. A loosely coupled water balance / limit-equilibrium analysis quantitatively illustrates the precarious nature of the active landslide zone at the site. The slope is shown to be unstable for a large suite of equally-likely scenarios. The analyses presented herein suggest that future work should include a rigorous characterization of pore-water pressure development, driven by comprehensive simulations of subsurface hydrologic response, to improve our understanding of slope failure initiation at the Devil's Slide site.

  7. You talkin' to me? Interactive playback is a powerful yet underused tool in animal communication research.

    PubMed

    King, Stephanie L

    2015-07-01

    Over the years, playback experiments have helped further our understanding of the wonderful world of animal communication. They have provided fundamental insights into animal behaviour and the function of communicative signals in numerous taxa. As important as these experiments are, however, there is strong evidence to suggest that the information conveyed in a signal may only have value when presented interactively. By their very nature, signalling exchanges are interactive and therefore, an interactive playback design is a powerful tool for examining the function of such exchanges. While researchers working on frog and songbird vocal interactions have long championed interactive playback, it remains surprisingly underused across other taxa. The interactive playback approach is not limited to studies of acoustic signalling, but can be applied to other sensory modalities, including visual, chemical and electrical communication. Here, I discuss interactive playback as a potent yet underused technique in the field of animal behaviour. I present a concise review of studies that have used interactive playback thus far, describe how it can be applied, and discuss its limitations and challenges. My hope is that this review will result in more scientists applying this innovative technique to their own study subjects, as a means of furthering our understanding of the function of signalling interactions in animal communication systems. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  8. An Open Source Simulation Model for Soil and Sediment Bioturbation

    PubMed Central

    Schiffers, Katja; Teal, Lorna Rachel; Travis, Justin Mark John; Solan, Martin

    2011-01-01

    Bioturbation is one of the most widespread forms of ecological engineering and has significant implications for the structure and functioning of ecosystems, yet our understanding of the processes involved in biotic mixing remains incomplete. One reason is that, despite their value and utility, most mathematical models currently applied to bioturbation data tend to neglect aspects of the natural complexity of bioturbation in favour of mathematical simplicity. At the same time, the abstract nature of these approaches limits the application of such models to a limited range of users. Here, we contend that a movement towards process-based modelling can improve both the representation of the mechanistic basis of bioturbation and the intuitiveness of modelling approaches. In support of this initiative, we present an open source modelling framework that explicitly simulates particle displacement and a worked example to facilitate application and further development. The framework combines the advantages of rule-based lattice models with the application of parameterisable probability density functions to generate mixing on the lattice. Model parameters can be fitted by experimental data and describe particle displacement at the spatial and temporal scales at which bioturbation data is routinely collected. By using the same model structure across species, but generating species-specific parameters, a generic understanding of species-specific bioturbation behaviour can be achieved. An application to a case study and comparison with a commonly used model attest the predictive power of the approach. PMID:22162997

  9. Stomatal structure and physiology do not explain differences in water use among montane eucalypts.

    PubMed

    Gharun, Mana; Turnbull, Tarryn L; Pfautsch, Sebastian; Adams, Mark A

    2015-04-01

    Understanding the regulation of water use at the whole-tree scale is critical to advancing the utility of physiological ecology, for example in its role in predictive hydrology of forested catchments. For three eucalypt species that dominate high-elevation catchments in south-eastern Australia, we examined if whole-tree water use could be related to three widely discussed regulators of water use: stomatal anatomy, sensitivity of stomata [i.e. stomatal conductance (g(s))] to environmental influences, and sapwood area. While daily tree water use varied sixfold among species, sap velocity and sapwood area varied in parallel. Combined, stomatal structure and physiology could not explain differences in species-specific water use. Species which exhibited the fastest (Eucalyptus delegatensis) and slowest (Eucalyptus pauciflora) rates of water use both exhibited greater capacity for physiological control of g(s) [indicated by sensitivity to vapour pressure deficit (VPD)] and a reduced capacity to limit g(s) anatomically [indicated by greater potential g(s) (g(max))]. Conversely, g(s) was insensitive to VPD and g(max) was lowest for Eucalyptus radiata, the species showing intermediate rates of water use. Improved knowledge of stomatal anatomy will help us to understand the capacity of species to regulate leaf-level water loss, but seems likely to remain of limited use for explaining rates of whole-tree water use in montane eucalypts at the catchment scale.

  10. An open source simulation model for soil and sediment bioturbation.

    PubMed

    Schiffers, Katja; Teal, Lorna Rachel; Travis, Justin Mark John; Solan, Martin

    2011-01-01

    Bioturbation is one of the most widespread forms of ecological engineering and has significant implications for the structure and functioning of ecosystems, yet our understanding of the processes involved in biotic mixing remains incomplete. One reason is that, despite their value and utility, most mathematical models currently applied to bioturbation data tend to neglect aspects of the natural complexity of bioturbation in favour of mathematical simplicity. At the same time, the abstract nature of these approaches limits the application of such models to a limited range of users. Here, we contend that a movement towards process-based modelling can improve both the representation of the mechanistic basis of bioturbation and the intuitiveness of modelling approaches. In support of this initiative, we present an open source modelling framework that explicitly simulates particle displacement and a worked example to facilitate application and further development. The framework combines the advantages of rule-based lattice models with the application of parameterisable probability density functions to generate mixing on the lattice. Model parameters can be fitted by experimental data and describe particle displacement at the spatial and temporal scales at which bioturbation data is routinely collected. By using the same model structure across species, but generating species-specific parameters, a generic understanding of species-specific bioturbation behaviour can be achieved. An application to a case study and comparison with a commonly used model attest the predictive power of the approach.

  11. Breast lesions of uncertain malignant nature and limited metastatic potential: Proposals to improve their recognition and clinical management

    PubMed Central

    Rakha, Emad A.; Badve, Sunil; Eusebi, Vincenzo; Reis-Filho, Jorge S.; Fox, Stephen B.; Dabbs, David J.; Decker, Thomas; Hodi, Zsolt; Ichihara, Shu; Lee, Andrew HS.; Palacios, José; Richardson, Andrea L.; Vincent-Salomon, Anne; Schmitt, Fernando C.; Tan, Puay-Hoon; Tse, Gary M.; Ellis, Ian O.

    2016-01-01

    Breast lesions comprise a family of heterogeneous entities with variable patterns of presentation, morphology and clinical behaviour. The majority of breast lesions are traditionally classified into benign and malignant conditions and their behaviour can, in the vast majority of cases, be predicted with a reasonable degree of accuracy. However, there remain lesions which show borderline features and lie in a grey-zone between benign and malignant as their behaviour cannot be predicted reliably. Defined pathological categorisation of such lesions is challenging and for some entities is recognised to be subjective and include a range of diagnoses, and forms of terminology, which may trigger over-treatment or under-treatment. The rarity of these lesions makes acquisition of clinical evidence problematic and limits the development of a sufficient evidence base to support informed decision making by clinicians and patients. Emerging molecular evidence is providing a greater understanding of the biology of these lesions, but this may or may not be reflected in their clinical behaviour. Herein we discuss some breast lesions that are associated with uncertainty regarding classification, behaviour and hence management. These include biologically invasive malignant lesions associated with uncertain metastatic potential such as low-grade adenosquamous carcinoma, low-grade fibromatosis-like spindle cell carcinoma and encapsulated papillary carcinoma. Other lesions remain of uncertain malignant nature such as mammary cylindroma, atypical microglandular adenosis, mammary pleomorphic adenoma and infiltrating epitheliosis. The concept of categories of 1) breast lesions of uncertain malignant nature and 2) breast lesions of limited metastatic potential, are proposed with details of which histological entities could be included in each category, and their management implications are discussed. PMID:26348644

  12. Export production in the New-Zealand region since the Last Glacial Maximum

    NASA Astrophysics Data System (ADS)

    Durand, Axel; Chase, Zanna; Noble, Taryn L.; Bostock, Helen; Jaccard, Samuel L.; Kitchener, Priya; Townsend, Ashley T.; Jansen, Nils; Kinsley, Les; Jacobsen, Geraldine; Johnson, Sean; Neil, Helen

    2017-07-01

    Increased export production (EP) in the Subantarctic Zone (SAZ) of the Southern Ocean due to iron fertilisation has been proposed as a key mechanism for explaining carbon drawdown during the last glacial maximum (LGM). This work reconstructs marine EP since the LGM at four sites around New Zealand. For the first time in this region, 230-Thorium-normalised fluxes of biogenic opal, carbonate, excess barium, and organic carbon are presented. In Subtropical Waters and the SAZ, these flux variations show that EP has not changed markedly since the LGM. The only exception is a site currently north of the subtropical front. Here we suggest the subtropical front shifted over the core site between 18 and 12 ka, driving increased EP. To understand why EP remained mostly low and constant elsewhere, lithogenic fluxes at the four sites were measured to investigate changes in dust deposition. At all sites, lithogenic fluxes were greater during the LGM compared to the Holocene. The positive temporal correlation between the Antarctic dust record and lithogenic flux at a site in the Tasman Sea shows that regionally, increased dust deposition contributed to the high glacial lithogenic fluxes. Additionally, it is inferred that lithogenic material from erosion and glacier melting deposited on the Campbell Plateau during the deglaciation (18-12 ka). From these observations, it is proposed that even though increased glacial dust deposition may have relieved iron limitation within the SAZ around New Zealand, the availability of silicic acid limited diatom growth and thus any resultant increase in carbon export during the LGM. Therefore, silicic acid concentrations have remained low since the LGM. This result suggests that both silicic acid and iron co-limit EP in the SAZ around New Zealand, consistent with modern process studies.

  13. Probabilistic cost estimates for climate change mitigation.

    PubMed

    Rogelj, Joeri; McCollum, David L; Reisinger, Andy; Meinshausen, Malte; Riahi, Keywan

    2013-01-03

    For more than a decade, the target of keeping global warming below 2 °C has been a key focus of the international climate debate. In response, the scientific community has published a number of scenario studies that estimate the costs of achieving such a target. Producing these estimates remains a challenge, particularly because of relatively well known, but poorly quantified, uncertainties, and owing to limited integration of scientific knowledge across disciplines. The integrated assessment community, on the one hand, has extensively assessed the influence of technological and socio-economic uncertainties on low-carbon scenarios and associated costs. The climate modelling community, on the other hand, has spent years improving its understanding of the geophysical response of the Earth system to emissions of greenhouse gases. This geophysical response remains a key uncertainty in the cost of mitigation scenarios but has been integrated with assessments of other uncertainties in only a rudimentary manner, that is, for equilibrium conditions. Here we bridge this gap between the two research communities by generating distributions of the costs associated with limiting transient global temperature increase to below specific values, taking into account uncertainties in four factors: geophysical, technological, social and political. We find that political choices that delay mitigation have the largest effect on the cost-risk distribution, followed by geophysical uncertainties, social factors influencing future energy demand and, lastly, technological uncertainties surrounding the availability of greenhouse gas mitigation options. Our information on temperature risk and mitigation costs provides crucial information for policy-making, because it clarifies the relative importance of mitigation costs, energy demand and the timing of global action in reducing the risk of exceeding a global temperature increase of 2 °C, or other limits such as 3 °C or 1.5 °C, across a wide range of scenarios.

  14. Renocardiac syndromes: physiopathology and treatment stratagems.

    PubMed

    Kingma, J G; Simard, D; Rouleau, J R

    2015-01-01

    Bidirectional inter-organ interactions are essential for normal functioning of the human body; however, they may also promote adverse conditions in remote organs. This review provides a narrative summary of the epidemiology, physiopathological mechanisms and clinical management of patients with combined renal and cardiac disease (recently classified as type 3 and 4 cardiorenal syndrome). Findings are also discussed within the context of basic research in animal models with similar comorbidities. Pertinent published articles were identified by literature search of PubMed, MEDLINE and Google Scholar. Additional data from studies in the author's laboratory were also consulted. The prevalence of renocardiac syndrome throughout the world is increasing in part due to an aging population and to other risk factors including hypertension, diabetes and dyslipidemia. Pathogenesis of this disorder involves multiple bidirectional interactions between the kidneys and heart; however, participation of other organs cannot be excluded. Our own work supports the hypothesis that the uremic milieu, caused by kidney dysfunction, produces major alterations in vasoregulatory control particularly at the level of the microvasculature that results in impaired oxygen delivery and blood perfusion. Recent clinical literature is replete with articles discussing the necessity to clearly define or characterize what constitutes cardiorenal syndrome in order to improve clinical management of affected patients. Patients are treated after onset of symptoms with limited available information regarding etiology. While understanding of mechanisms involved in pathogenesis of inter-organ crosstalk remains a challenging objective, basic research data remains limited partly because of the lack of animal models. Preservation of microvascular integrity may be the most critical factor to limit progression of multi-organ disorders including renocardiac syndrome. More fundamental studies are needed to help elucidate physiopathological mechanisms and for development of treatments to improve clinical outcomes.

  15. Mathematical modeling of intraperitoneal drug delivery: simulation of drug distribution in a single tumor nodule.

    PubMed

    Steuperaert, Margo; Falvo D'Urso Labate, Giuseppe; Debbaut, Charlotte; De Wever, Olivier; Vanhove, Christian; Ceelen, Wim; Segers, Patrick

    2017-11-01

    The intraperitoneal (IP) administration of chemotherapy is an alternative treatment for peritoneal carcinomatosis, allowing for higher intratumor concentrations of the cytotoxic agent compared to intravenous administration. Nevertheless, drug penetration depths are still limited to a few millimeters. It is thus necessary to better understand the limiting factors behind this poor penetration in order to improve IP chemotherapy delivery. By developing a three-dimensional computational fluid dynamics (CFD) model for drug penetration in a tumor nodule, we investigated the impact of a number of key parameters on the drug transport and penetration depth during IP chemotherapy. Overall, smaller tumors showed better penetration than larger ones, which could be attributed to the lower IFP in smaller tumors. Furthermore, the model demonstrated large improvements in penetration depth by subjecting the tumor nodules to vascular normalization therapy, and illustrated the importance of the drug that is used for therapy. Explicitly modeling the necrotic core had a limited effect on the simulated penetration. Similarly, the penetration depth remained virtually constant when the Darcy permeability of the tissue changed. Our findings illustrate that the developed parametrical CFD model is a powerful tool providing more insight in the drug transport and penetration during IP chemotherapy.

  16. Semantic Likelihood Models for Bayesian Inference in Human-Robot Interaction

    NASA Astrophysics Data System (ADS)

    Sweet, Nicholas

    Autonomous systems, particularly unmanned aerial systems (UAS), remain limited in au- tonomous capabilities largely due to a poor understanding of their environment. Current sensors simply do not match human perceptive capabilities, impeding progress towards full autonomy. Recent work has shown the value of humans as sources of information within a human-robot team; in target applications, communicating human-generated 'soft data' to autonomous systems enables higher levels of autonomy through large, efficient information gains. This requires development of a 'human sensor model' that allows soft data fusion through Bayesian inference to update the probabilistic belief representations maintained by autonomous systems. Current human sensor models that capture linguistic inputs as semantic information are limited in their ability to generalize likelihood functions for semantic statements: they may be learned from dense data; they do not exploit the contextual information embedded within groundings; and they often limit human input to restrictive and simplistic interfaces. This work provides mechanisms to synthesize human sensor models from constraints based on easily attainable a priori knowledge, develops compression techniques to capture information-dense semantics, and investigates the problem of capturing and fusing semantic information contained within unstructured natural language. A robotic experimental testbed is also developed to validate the above contributions.

  17. Closing in on the limits of life through open-access instrumentation.

    NASA Astrophysics Data System (ADS)

    Girguis, P. R.; Hoer, D.

    2016-12-01

    Put simply, metabolic activity by living organisms can discriminate against elemental isotopes, resulting in an isotopic fractionation that is manifest in their biomolecules, substrates and endproducts. For decades, investigators have used these isotope ratios to make inferences about organismal activity and physiological capacity in modern day and paleo-environments. However, a long standing challenge in the life sciences is identifying and characterizing the limits of life. Whereas the limits of metazoan (animal) life are known to some degree, the extent of microbial life remains unconstrained. For example, we do not know the upper temperature limits of life, nor the lower energy limits of life. Discrete samples and the subsequent geochemical and biological measurements provide a means of bounding these questions, but there are major challenges associated with collecting such samples from the deep sea and other "extreme" habitats. A complementary approach is in situ geo-referenced isotope mapping. To date, we have developed instruments capable of measuring methane-carbon isotope ratios in situ and used the to "map" the activity and influence of anaerobic methanotrophs around natural hydrocarbon seeps (Wankel et al., 2012). While these instruments provide isotopic data in realtime, their greatest value is in producing geo-referenced "maps" of these isotope ratios, enabling investigators to better understand where microbial activity is highest, and the extent to which methane-derived carbon is found in the neighboring sediments and overlying water column. Now, our efforts are aimed at developing a 2nd generation instrument that will be substantially smaller and far more energy efficient, enabling deployment in more challenging environments such as boreholes and beneath ice. Most importantly, we are designing it to be capable of quantifying differences in the isotopes of multiple volatile compounds, e.g. carbon and sulfur, enabling a greater degree of fidelity in detecting biological activity in the subsurface and in other challenging locales. Here we will present our designs and data, and discuss how this and other instruments -such as integrated autonomous sensor and sampling packages- can advance our understanding of the limits of life here on Earth and -potentially- on other bodies.

  18. App Usage Factor: A Simple Metric to Compare the Population Impact of Mobile Medical Apps

    PubMed Central

    Wyatt, Jeremy C

    2015-01-01

    Background One factor when assessing the quality of mobile apps is quantifying the impact of a given app on a population. There is currently no metric which can be used to compare the population impact of a mobile app across different health care disciplines. Objective The objective of this study is to create a novel metric to characterize the impact of a mobile app on a population. Methods We developed the simple novel metric, app usage factor (AUF), defined as the logarithm of the product of the number of active users of a mobile app with the median number of daily uses of the app. The behavior of this metric was modeled using simulated modeling in Python, a general-purpose programming language. Three simulations were conducted to explore the temporal and numerical stability of our metric and a simulated app ecosystem model using a simulated dataset of 20,000 apps. Results Simulations confirmed the metric was stable between predicted usage limits and remained stable at extremes of these limits. Analysis of a simulated dataset of 20,000 apps calculated an average value for the app usage factor of 4.90 (SD 0.78). A temporal simulation showed that the metric remained stable over time and suitable limits for its use were identified. Conclusions A key component when assessing app risk and potential harm is understanding the potential population impact of each mobile app. Our metric has many potential uses for a wide range of stakeholders in the app ecosystem, including users, regulators, developers, and health care professionals. Furthermore, this metric forms part of the overall estimate of risk and potential for harm or benefit posed by a mobile medical app. We identify the merits and limitations of this metric, as well as potential avenues for future validation and research. PMID:26290093

  19. Advances in Alzheimer's Diagnosis and Therapy: The Implications of Nanotechnology.

    PubMed

    Hajipour, Mohammad Javad; Santoso, Michelle R; Rezaee, Farhad; Aghaverdi, Haniyeh; Mahmoudi, Morteza; Perry, George

    2017-10-01

    Alzheimer's disease (AD) is a type of dementia that causes major issues for patients' memory, thinking, and behavior. Despite efforts to advance AD diagnostic and therapeutic tools, AD remains incurable due to its complex and multifactorial nature and lack of effective diagnostics/therapeutics. Nanoparticles (NPs) have demonstrated the potential to overcome the challenges and limitations associated with traditional diagnostics/therapeutics. Nanotechnology is now offering new tools and insights to advance our understanding of AD and eventually may offer new hope to AD patients. Here, we review the key roles of nanotechnologies in the recent literature, in both diagnostic and therapeutic aspects of AD, and discuss how these achievements may improve patient prognosis and quality of life. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Neural Plasticity following Abacus Training in Humans: A Review and Future Directions

    PubMed Central

    Li, Yongxin; Chen, Feiyan; Huang, Wenhua

    2016-01-01

    The human brain has an enormous capacity to adapt to a broad variety of environmental demands. Previous studies in the field of abacus training have shown that this training can induce specific changes in the brain. However, the neural mechanism underlying these changes remains elusive. Here, we reviewed the behavioral and imaging findings of comparisons between abacus experts and average control subjects and focused on changes in activation patterns and changes in brain structure. Finally, we noted the limitations and the future directions of this field. We concluded that although current studies have provided us with information about the mechanisms of abacus training, more research on abacus training is needed to understand its neural impact. PMID:26881089

  1. Coronal Heating and the Need for High-Resolution Observations

    NASA Technical Reports Server (NTRS)

    Klimchuk, James A.

    2008-01-01

    Despite excellent progress in recent years in understanding coronal heating, there remain many crucial questions that are still unanswered. Limitations in the observations are one important reason. Both theoretical and observational considerations point to the importance of small spatial scales, impulsive energy release, strong dynamics, and extreme plasma nonuniformity. As a consequence, high spatial resolution, broad temperature coverage, high temperature fidelity, and sensitivity to velocities and densities are all critical observational parameters. Current instruments lack one or more of these properties, and this has led to considerable ambiguity and confusion. In this talk, I will discuss recent ideas about coronal heating and emphasize that high spatial resolution observations, especially spectroscopic observations, are needed to make major progress on this important problem.

  2. Large Scale Deformation of the Western US Cordillera

    NASA Technical Reports Server (NTRS)

    Bennett, Richard A.

    2001-01-01

    Destructive earthquakes occur throughout the western US Cordillera (WUSC), not just within the San Andreas fault zone. But because we do not understand the present-day large-scale deformations of the crust throughout the WUSC, our ability to assess the potential for seismic hazards in this region remains severely limited. To address this problem, we are using a large collection of Global Positioning System (GPS) networks which spans the WUSC to precisely quantify present-day large-scale crustal deformations in a single uniform reference frame. Our work can roughly be divided into an analysis of the GPS observations to infer the deformation field across and within the entire plate boundary zone and an investigation of the implications of this deformation field regarding plate boundary dynamics.

  3. Assessment of patient support surfaces: principle, practice and limitations.

    PubMed

    Rithalia, S

    2005-01-01

    Pressure ulcers cause great pain and suffering to patients as well as unnecessary strain on nursing staff. Their treatment is both costly and time consuming. Every effort therefore should be directed towards their prevention. Understanding of the aetiology of pressure ulcers is still incomplete and assessment of devices aimed at prevention is difficult. Over the years, numerous parameters, including interface pressure and transcutaneous blood gas measurements, have been used to evaluate mattresses and cushions. However, the quality of the data gathered is variable and its clinical interpretation remains unsatisfactory. It could be said that the science of evaluation of support surfaces is still at a formative stage, as clinical validation of many of the approaches has yet to be carried out.

  4. Identifying vaccine targets for anti-leishmanial vaccine development

    PubMed Central

    Sundar, Shyam; Singh, Bhawana

    2014-01-01

    Leishmaniasis is a neglected tropical disease spread by an arthropod vector. It remains a significant health problem with an incidence of 0.2–0.4 million VL and 0.7–1.2 million CL cases each year. There are limitations associated with the current therapeutic regimens for leishmaniasis and the fact that after recovery from infection the host becomes immune to subsequent infection therefore, these factors forces the feasibility of a vaccine for leishmaniasis. Publication of the genome sequence of Leishmania has paved a new way to understand the pathogenesis and host immunological status therefore providing a deep insight in the field of vaccine research. This review is an effort to study the antigenic targets in Leishmania to develop anti-leishmanial vaccine. PMID:24606556

  5. Regulatory perspectives on acceptability testing of dosage forms in children.

    PubMed

    Kozarewicz, Piotr

    2014-08-05

    Current knowledge about the age-appropriateness of different dosage forms is still fragmented or limited. Applicants are asked to demonstrate that the target age group(s) can manage the dosage form or propose an alternative strategy. However, questions remain about how far the applicant must go and what percentage of patients must find the strategy 'acceptable'. The aim of this overview is to provide an update on current thinking and understanding of the problem, and discuss issues relating to the acceptability testing. This overview should be considered as means to start a wider discussion which hopefully will result in a harmonised, globally acceptable approach for confirmation of the acceptability in the future. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Advances in understanding Giardia: determinants and mechanisms of chronic sequelae

    PubMed Central

    Sartor, R. Balfour

    2015-01-01

    Giardia lamblia is a flagellated protozoan that is the most common cause of intestinal parasitic infection in children living in resource-limited settings. The pathogenicity of Giardia has been debated since the parasite was first identified, and clinical outcomes vary across studies. Among recent perplexing findings are diametrically opposed associations between Giardia and acute versus persistent diarrhea and a poorly understood potential for long-term sequelae, including impaired child growth and cognitive development. The mechanisms driving these protean clinical outcomes remain elusive, but recent advances suggest that variability in Giardia strains, host nutritional status, the composition of microbiota, co-infecting enteropathogens, host genetically determined mucosal immune responses, and immune modulation by Giardia are all relevant factors influencing disease manifestations after Giardia infection. PMID:26097735

  7. Comparison of aged polyamide powders for selective laser sintering

    NASA Astrophysics Data System (ADS)

    Martínez, A.; Ibáñez, A.; Sánchez, A.; León, M. A.

    2012-04-01

    Selective Laser Sintering (SLS) is an additive manufacturing technology in which a three-dimensional object is manufactured layer by layer by melting powder materials with heat generated from a CO2 laser. However, a disadvantage of sintered materials is that the unsintered powder material during the process can be reused only a limited number of cycles, as during the heating phase in the sintering chamber the material remains at a temperature near the fusion point for a certain period of time and lose properties. This work shows the study of two polyamides (PA12)-based powders used in SLS with the aim of understanding the modification of their properties mainly with the temperature and the time at which they are exposed during the processing.

  8. Universal Health Coverage and Primary Healthcare: Lessons From Japan

    PubMed Central

    Bloom, Gerald

    2017-01-01

    A recent editorial by Naoki Ikegami has proposed three key lessons from Japan’s experience of achieving virtually universal coverage with primary healthcare services: the need to integrate the existing providers of primary healthcare services into the organised health system; the need to limit government commitments to finance hospital services and the need to empower providers of primary healthcare to influence decisions that influence their livelihoods. Although the context of low- and middle-income countries (LMICs) differs in many ways from Japan in the late 19th and early 20th centuries, the lesson that short-term initiatives to achieve universal coverage need to be complemented by an understanding of the factors influencing long-term change management remains highly relevant. PMID:28812806

  9. Friction Syndromes of the Knee: The Iliotibial Band and Anterior Fat Pads.

    PubMed

    Wissman, Robert D; Pomeranz, Stephen J

    2018-01-01

    As participation in sporting activities increases among the general population, the incidence of overuse injuries continues to rise. Friction syndromes of the knee are common and are often clinically diagnosed without the need for imaging. However, clinical symptoms may overlap with other joint abnormalities, and physical examination may be limited in individuals with excessive pain. Magnetic resonance imaging has remained the modality of choice for the evaluation of internal derangements of the joints and is a useful aid in the diagnosis of friction syndrome of the knee. This case report provides clinicians with an understanding of the most common friction syndromes of the knee joint as well as their imaging findings. (Journal of Surgical Orthopaedic Advances 27(1):77-80, 2018).

  10. 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

  11. Acute myeloid leukemia targets for bispecific antibodies

    PubMed Central

    Hoseini, S S; Cheung, N K

    2017-01-01

    Despite substantial gains in our understanding of the genomics of acute myelogenous leukemia (AML), patient survival remains unsatisfactory especially among the older age group. T cell-based therapy of lymphoblastic leukemia is rapidly advancing; however, its application in AML is still lagging behind. Bispecific antibodies can redirect polyclonal effector cells to engage chosen targets on leukemia blasts. When the effector cells are natural-killer cells, both antibody-dependent and antibody-independent mechanisms could be exploited. When the effectors are T cells, direct tumor cytotoxicity can be engaged followed by a potential vaccination effect. In this review, we summarize the AML-associated tumor targets and the bispecific antibodies that have been studied. The potentials and limitations of each of these systems will be discussed. PMID:28157217

  12. Meeting Report: The Role of the Mobilome in Cancer

    PubMed Central

    Ardeljan, Daniel; Taylor, Martin S.; Burns, Kathleen H.; Boeke, Jef D.; Espey, Michael Graham; Woodhouse, Elisa C.; Howcroft, T. Kevin

    2016-01-01

    Approximately half of the human genome consists of repetitive sequence attributed to the activities of mobile DNAs, including DNA transposons, RNA transposons, and endogenous retroviruses. Of these, only Long INterspersed Elements (LINE-1 or L1) and sequences copied by LINE-1 remain mobile in our species today. Although cells restrict L1 activity by both transcriptional and post-transcriptional mechanisms, L1 de-repression occurs in developmental and pathologic contexts, including many types of cancers. However, we have limited knowledge of the extent and consequences of L1 expression in premalignancies and cancer. Participants in this NIH strategic workshop considered key questions to enhance our understanding of mechanisms and roles the mobilome may play in cancer biology. PMID:27527733

  13. Visfatin and cardio-cerebro-vascular disease.

    PubMed

    Wang, Pei; Vanhoutte, Paul M; Miao, Chao-Yu

    2012-01-01

    Nicotinamide phosphoribosyltransferase is the rate-limiting enzyme that catalyzes the first step in the biosynthesis of nicotinamide adenine dinucleotide from nicotinamide. This protein was originally cloned as a putative pre-B cell colony-enhancing factor and also found to be a visceral fat-derived adipokine (visfatin). As a multifunctional protein, visfatin plays an important role in immunity, metabolism, aging, inflammation, and responses to stress. Visfatin also participates in several pathophysiological processes contributing to cardio-cerebro-vascular diseases, including hypertension, atherosclerosis, ischemic heart disease, and ischemic stroke. However, whether visfatin is a friend or a foe in these diseases remains uncertain. This brief review focuses on the current understanding of the complex role of visfatin in the cardio-cerebro-vascular system under normal and pathophysiological conditions.

  14. Understanding Possibilities and Limitations of Abstract Chemical Representations for Achieving Conceptual Understanding

    ERIC Educational Resources Information Center

    Corradi, David M. J.; Elen, Jan; Schraepen, Beno; Clarebout, Geraldine

    2014-01-01

    When learning with abstract and scientific multiple external representations (MERs), low prior knowledge learners are said to have difficulties in using these MERs to achieve conceptual understanding. Yet little is known about what these limitations precisely entail. In order to understand this, we presented 101 learners with low prior knowledge…

  15. Three Concepts or One? Students' Understanding of Basic Limit Concepts

    ERIC Educational Resources Information Center

    Fernández-Plaza, José Antonio; Simpson, Adrian

    2016-01-01

    In many mathematics curricula, the notion of limit is introduced three times: the limit of a sequence, the limit of a function at a point and the limit of a function at infinity. Despite the use of very similar symbols, few connections between these notions are made explicitly and few papers in the large literature on student understanding of…

  16. Ocular melanoma: an overview of the current status

    PubMed Central

    Jovanovic, Predrag; Mihajlovic, Marija; Djordjevic-Jocic, Jasmina; Vlajkovic, Slobodan; Cekic, Sonja; Stefanovic, Vladisav

    2013-01-01

    Ocular melanoma is the second most common type of melanoma after cutaneous and the most common primary intraocular malignant tumor in adults. Large majority of ocular melanomas originate from uvea, while conjunctival melanomas are far less frequent. Incidence of uveal melanoma has remained stable over last three decades. Diagnosis is in most cases established by clinical examination with great accuracy. Local treatment of uveal melanoma has improved, with increased use of conservative methods and preservation of the eye, but survival rates have remained unchanged. Recent advances in cytogenetics and genetics enhanced prognostication and enabled to determine tumors with high metastatic potential. However, due to lack of effective systemic therapy, prognosis of patients with metastasis remains poor and metastatic disease remains the leading cause of death among patients with uveal melanoma. Conjunctival melanoma is rare, but its incidence is increasing. It mostly occurs among white adults. In majority of cases it originates from preceding primary acquired melanosis. Current standard treatment for conjunctival melanoma is wide local excision with adjuvant therapy, including brachytherapy, cryotherapy and topical application of chemotherapeutic agent. Rarity of this tumor limits conduction of controlled trials to define the best treatment modality. As well as for uveal melanoma, prognosis of patients with metastasis is poor because there is no effective systemic therapy. Better understanding of underlying genetic and molecular abnormalities implicated in development and progression of ocular melanomas provides a great opportunity for development of targeted therapy, which will hopefully improve prognosis of patients with metastatic disease. PMID:23826405

  17. Does Conceptual Understanding of Limit Partially Lead Students to Misconceptions?

    NASA Astrophysics Data System (ADS)

    Mulyono, B.; Hapizah

    2017-09-01

    This article talks about the result of preliminary research of my dissertation, which will investigate student’s retention of conceptual understanding. In my preliminary research, I surveyed 73 students of mathematics education program by giving some questions to test their retention of conceptual understanding of limits. Based on the results of analyzing of students’ answers I conclude that most of the students have problems with their retention of conceptual understanding and they also have misconception of limits. The first misconception I identified is that students always used the substitution method to determine a limit of a function at a point, but they did not check whether the function is continue or not at the point. It means that they only use the substitution theorem partially, because they do not consider that the substitution theorem \\mathop{{lim}}\\limits\\text{x\\to \\text{c}}f(x)=f(c) works only if f(x) is defined at χ = c. The other misconception identified is that some students always think there must be available of variables χ in a function to determine the limit of the function. I conjecture that conceptual understanding of limit partially leads students to misconceptions.

  18. Role of tropical Indian and Atlantic Oceans variability on ENSO

    NASA Astrophysics Data System (ADS)

    Prodhomme, Chloé; Terray, Pascal; Masson, Sebastien; Boschat, Ghyslaine

    2014-05-01

    There are strong evidences of an interaction between tropical Indian, Atlantic and Pacific Oceans. Nevertheless, these interactions remain deeply controversial. While some authors claim the tropical Indian and Atlantic oceans only play a passive role with respect to ENSO, others suggest a driving role for these two basins on ENSO. The mecanisms underlying these relations are not fully understood and, in the Indian Ocean, the possible role of both modes of tropical variability (the Indian Ocean Dipole (IOD) and the Indian Ocean Basin mode (IOB)) remain unclear. To better quantify and understand how the variability of the tropical Indian and Atlantic Oceans impact ENSO variability, we performed two sensitivity experiments using the SINTEX-F2 coupled model. For each experiment, we suppressed the variability of SST and the air-sea coupling in either the tropical Indian Ocean or tropical Atlantic Ocean by applying a strong nudging of the SST to the observed SST climatology. In both experiments, the ENSO periodicity increases. In the Atlantic experiment, our understanding of this increased periodicity is drastically limited by the strongly biased mean state in this region. Conversely, in the Indian Ocean experiment, the increase of ENSO periodicity is related to the absence of the IOB following the El Niño peak, which leads to a decrease of westerly winds in the western Pacific during late winter and spring after the peak. These weaker westerlies hinders the transition to a La Niña phase and thus increase the duration and periodicity of the event.

  19. Exploring the potential of open big data from ticketing websites to characterize travel patterns within the Chinese high-speed rail system

    PubMed Central

    Luan, Xiali; Han, Shanrui; Zhou, Wen

    2017-01-01

    Big data have contributed to deepen our understanding in regards to many human systems, particularly human mobility patterns and the structure and functioning of transportation systems. Resonating the recent call for ‘open big data,’ big data from various sources on a range of scales have become increasingly accessible to the public. However, open big data relevant to travelers within public transit tools remain scarce, hindering any further in-depth study on human mobility patterns. Here, we explore ticketing-website derived data that are publically available but have been largely neglected. We demonstrate the power, potential and limitations of this open big data, using the Chinese high-speed rail (HSR) system as an example. Using an application programming interface, we automatically collected the data on the remaining tickets (RTD) for scheduled trains at the last second before departure in order to retrieve information on unused transit capacity, occupancy rate of trains, and passenger flux at stations. We show that this information is highly useful in characterizing the spatiotemporal patterns of traveling behaviors on the Chinese HSR, such as weekend traveling behavior, imbalanced commuting behavior, and station functionality. Our work facilitates the understanding of human traveling patterns along the Chinese HSR, and the functionality of the largest HSR system in the world. We expect our work to attract attention regarding this unique open big data source for the study of analogous transportation systems. PMID:28574991

  20. Mitochondrial introgression via ancient hybridization, and systematics of the Australian endemic pygopodid gecko genus Delma.

    PubMed

    Brennan, Ian G; Bauer, Aaron M; Jackman, Todd R

    2016-01-01

    Of the more than 1500 species of geckos found across six continents, few remain as unfamiliar as the pygopodids - Family Pygopodidae (Gray, 1845). These gekkotans are limited to Australia (44 species) and New Guinea (2 species), but have diverged extensively into the most ecologically diverse limbless radiation save Serpentes. Current phylogenetic understanding of the family has relied almost exclusively on two works, which have produced and synthesized an immense amount of morphological, geographical, and molecular data. However, current interspecific relationships within the largest genus Delma Gray 1831 are based chiefly upon data from two mitochondrial loci (16s, ND2). Here, we reevaluate the interspecific relationships within the genus Delma using two mitochondrial and four nuclear loci (RAG1, MXRA5, MOS, DYNLL1), and identify points of strong conflict between nuclear and mitochondrial genomic data. We address mito-nuclear discordance, and remedy this conflict by recognizing several points of mitochondrial introgression as the result of ancient hybridization events. Owing to the legacy value and intraspecific informativeness, we suggest the continued use of ND2 as a phylogenetic marker. Results identify strong support for species groups, but relationships among these clades, and the placement of several enigmatic taxa remain uncertain. We suggest a more careful review of Delma australis and the 'northwest Australia' clade. Accurately assessing and addressing species richness and relationships within this endemic Australian Gekkotan genus is relevant for understanding patterns of squamate speciation across the region. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Symbiotic or parasitic? A review of the literature on the impact of fellowships on surgical residents.

    PubMed

    Plerhoples, Timothy A; Greco, Ralph S; Krummel, Thomas M; Melcher, Marc L

    2012-12-01

    We conducted a systematic review of published literature to gain a better understanding of the impact of advanced fellowships on surgical resident training and education. As fellowship opportunities rise, resident training may be adversely impacted. PubMed, MEDLINE, Scopus, BIOSIS, Web of Science, and a manual search of article bibliographies. Of the 139 citations identified through the initial electronic search and screened for possible inclusion, 23 articles were retained and accepted for this review. Data were extracted regarding surgical specialty, methodology, sample population, outcomes measured, and results. Eight studies retrospectively compared the eras before and after the introduction of a fellowship or trended data over time. Approximately half used data from a single institution, whereas the other half used some form of national data or survey. Only 3 studies used national case data. Fourteen studies looked at general surgery, 6 at obstetrics-gynecology, 2 at urology, and 1 at otolaryngology. Only one study concluded that fellowships have a generally positive impact on resident education, whereas 9 others found a negative impact. The remaining 13 studies found mixed results (n = 6) or minimal to no impact (n = 7). The overall impact of advanced surgical fellowships on surgical resident education and training remains unclear, as most studies rely on limited data of questionable generalizability. A careful study of the national database of surgery resident case logs is essential to better understand how early surgical specialization and fellowships will impact the future of general surgery education.

  2. Exploring the potential of open big data from ticketing websites to characterize travel patterns within the Chinese high-speed rail system.

    PubMed

    Wei, Sheng; Yuan, Jinfu; Qiu, Yanning; Luan, Xiali; Han, Shanrui; Zhou, Wen; Xu, Chi

    2017-01-01

    Big data have contributed to deepen our understanding in regards to many human systems, particularly human mobility patterns and the structure and functioning of transportation systems. Resonating the recent call for 'open big data,' big data from various sources on a range of scales have become increasingly accessible to the public. However, open big data relevant to travelers within public transit tools remain scarce, hindering any further in-depth study on human mobility patterns. Here, we explore ticketing-website derived data that are publically available but have been largely neglected. We demonstrate the power, potential and limitations of this open big data, using the Chinese high-speed rail (HSR) system as an example. Using an application programming interface, we automatically collected the data on the remaining tickets (RTD) for scheduled trains at the last second before departure in order to retrieve information on unused transit capacity, occupancy rate of trains, and passenger flux at stations. We show that this information is highly useful in characterizing the spatiotemporal patterns of traveling behaviors on the Chinese HSR, such as weekend traveling behavior, imbalanced commuting behavior, and station functionality. Our work facilitates the understanding of human traveling patterns along the Chinese HSR, and the functionality of the largest HSR system in the world. We expect our work to attract attention regarding this unique open big data source for the study of analogous transportation systems.

  3. A Taxonomy of Fatigue Concepts and Their Relation to Hearing Loss

    PubMed Central

    Hornsby, Benjamin W.Y.; Naylor, Graham; Bess, Fred H.

    2016-01-01

    Fatigue is common in individuals with a variety of chronic health conditions and can have significant negative effects on quality of life. Although limited in scope, recent work suggests persons with hearing loss may be at increased risk for fatigue, in part due to effortful listening that is exacerbated by their hearing impairment. However, the mechanisms responsible for hearing loss-related fatigue, and the efficacy of audiologic interventions for reducing fatigue, remain unclear. To improve our understanding of hearing loss-related fatigue, as a field it is important to develop a common conceptual understanding of this construct. In this paper the broader fatigue literature is reviewed to identify and describe core constructs, consequences and methods for assessing fatigue and related constructs. Finally, our current knowledge linking hearing loss and fatigue is described and may be summarised as follows: Hearing impairment increases the risk of subjective fatigue and vigor deficits.Adults with hearing loss require more time to recover from fatigue after work, and have more work absences.Sustained, effortful, listening can be fatiguing.Optimal methods for eliciting and measuring fatigue in persons with hearing loss remain unclear and may vary with listening condition.Amplification may minimize decrements in cognitive processing speed during sustained effortful listening. Future research is needed to develop reliable measurement methods to quantify hearing loss-related fatigue; explore factors responsible for modulating fatigue in people with hearing loss; and identify and evaluate potential interventions for reducing hearing loss-related fatigue. PMID:27355763

  4. A Perspective on Micro-Evo-Devo: Progress and Potential

    PubMed Central

    Nunes, Maria D. S.; Arif, Saad; Schlötterer, Christian; McGregor, Alistair P.

    2013-01-01

    The term “micro-evo-devo” refers to the combined study of the genetic and developmental bases of natural variation in populations and the evolutionary forces that have shaped this variation. It thus represents a synthesis of the fields of evolutionary developmental biology and population genetics. As has been pointed out by several others, this synthesis can provide insights into the evolution of organismal form and function that have not been possible within these individual disciplines separately. Despite a number of important successes in micro-evo-devo, however, it appears that evo devo and population genetics remain largely separate spheres of research, limiting their ability to address evolutionary questions. This also risks pushing contemporary evo devo to the fringes of evolutionary biology because it does not describe the causative molecular changes underlying evolution or the evolutionary forces involved. Here we reemphasize the theoretical and practical importance of micro-evo-devo as a strategy for understanding phenotypic evolution, review the key recent insights that it has provided, and present a perspective on both the potential and the remaining challenges of this exciting interdisciplinary field. PMID:24190920

  5. A review of soft-tissue sarcomas: translation of biological advances into treatment measures

    PubMed Central

    Mann, Michael J; Tolani, Bhairavi

    2018-01-01

    Soft-tissue sarcomas are rare malignant tumors arising from connective tissues and have an overall incidence of about five per 100,000 per year. While this diverse family of malignancies comprises over 100 histological subtypes and many molecular aberrations are prevalent within specific sarcomas, very few are therapeutically targeted. Instead of utilizing molecular signatures, first-line sarcoma treatment options are still limited to traditional surgery and chemotherapy, and many of the latter remain largely ineffective and are plagued by disease resistance. Currently, the mechanism of sarcoma oncogenesis remains largely unknown, thus necessitating a better understanding of pathogenesis. Although substantial progress has not occurred with molecularly targeted therapies over the past 30 years, increased knowledge about sarcoma biology could lead to new and more effective treatment strategies to move the field forward. Here, we discuss biological advances in the core molecular determinants in some of the most common soft-tissue sarcomas – liposarcoma, angiosarcoma, leiomyosarcoma, rhabdomyosarcoma, Ewing’s sarcoma, and synovial sarcoma – with an emphasis on emerging genomic and molecular pathway targets and immunotherapeutic treatment strategies to combat this confounding disease. PMID:29785138

  6. Pleiotropic roles of the matricellular protein Sparc in tendon maturation and ageing

    PubMed Central

    Gehwolf, Renate; Wagner, Andrea; Lehner, Christine; Bradshaw, Amy D.; Scharler, Cornelia; Niestrawska, Justyna A.; Holzapfel, Gerhard A.; Bauer, Hans-Christian; Tempfer, Herbert; Traweger, Andreas

    2016-01-01

    Acute and chronic tendinopathies remain clinically challenging and tendons are predisposed to degeneration or injury with age. Despite the high prevalence of tendon disease in the elderly, our current understanding of the mechanisms underlying the age-dependent deterioration of tendon function remains very limited. Here, we show that Secreted protein acidic and rich in cysteine (Sparc) expression significantly decreases in healthy-aged mouse Achilles tendons. Loss of Sparc results in tendon collagen fibrillogenesis defects and Sparc−/− tendons are less able to withstand force in comparison with their respective wild type counterparts. On the cellular level, Sparc-null and healthy-aged tendon-derived cells exhibited a more contracted phenotype and an altered actin cytoskeleton. Additionally, an elevated expression of the adipogenic marker genes PPARγ and Cebpα with a concomitant increase in lipid deposits in aged and Sparc−/− tendons was observed. In summary, we propose that Sparc levels in tendons are critical for proper collagen fibril maturation and its age-related decrease, together with a change in ECM properties favors lipid accretion in tendons. PMID:27586416

  7. Anticipated classes of new medications and molecular targets for pulmonary arterial hypertension

    PubMed Central

    Morrell, Nicholas W.; Archer, Stephen L.; DeFelice, Albert; Evans, Steven; Fiszman, Monica; Martin, Thomas; Saulnier, Muriel; Rabinovitch, Marlene; Schermuly, Ralph; Stewart, Duncan; Truebel, Hubert; Walker, Gennyne; Stenmark, Kurt R.

    2013-01-01

    Pulmonary arterial hypertension (PAH) remains a life-limiting condition with a major impact on the ability to lead a normal life. Although existing therapies may improve the outlook in some patients there remains a major unmet need to develop more effective therapies in this condition. There have been significant advances in our understanding of the genetic, cell and molecular basis of PAH over the last few years. This research has identified important new targets that could be explored as potential therapies for PAH. In this review we discuss whether further exploitation of vasoactive agents could bring additional benefits over existing approaches. Approaches to enhance smooth muscle cell apotosis and the potential of receptor tyrosine kinase inhibition are summarised. We evaluate the role of inflammation, epigenetic changes and altered glycolytic metabolism as potential targets for therapy, and whether inherited genetic mutations in PAH have revealed druggable targets. The potential of cell based therapies and gene therapy are also discussed. Potential candidate pathways that could be explored in the context of experimental medicine are identified. PMID:23662201

  8. Human-mediated extirpation of the unique Chatham Islands sea lion and implications for the conservation management of remaining New Zealand sea lion populations.

    PubMed

    Rawlence, Nicolas J; Collins, Catherine J; Anderson, Christian N K; Maxwell, Justin J; Smith, Ian W G; Robertson, Bruce C; Knapp, Michael; Horsburgh, Katherine Ann; Stanton, Jo-Ann L; Scofield, R Paul; Tennyson, Alan J D; Matisoo-Smith, Elizabeth A; Waters, Jonathan M

    2016-08-01

    While terrestrial megafaunal extinctions have been well characterized worldwide, our understanding of declines in marine megafauna remains limited. Here, we use ancient DNA analyses of prehistoric (<1450-1650 AD) sea lion specimens from New Zealand's isolated Chatham Islands to assess the demographic impacts of human settlement. These data suggest there was a large population of sea lions, unique to the Chatham Islands, at the time of Polynesian settlement. This distinct mitochondrial lineage became rapidly extinct within 200 years due to overhunting, paralleling the extirpation of a similarly large endemic mainland population. Whole mitogenomic analyses confirm substantial intraspecific diversity among prehistoric lineages. Demographic models suggest that even low harvest rates would likely have driven rapid extinction of these lineages. This study indicates that surviving Phocarctos populations are remnants of a once diverse and widespread sea lion assemblage, highlighting dramatic human impacts on endemic marine biodiversity. Our findings also suggest that Phocarctos bycatch in commercial fisheries may contribute to the ongoing population decline. © 2016 John Wiley & Sons Ltd.

  9. Experimental demonstration of the importance of competition under disturbance.

    PubMed

    Violle, Cyrille; Pu, Zhichao; Jiang, Lin

    2010-07-20

    Ecologists have long recognized the roles of competition and disturbance in shaping ecological communities, and the combinatorial effects of these two factors have been the subject of substantial ecological research. Nevertheless, it is still unclear whether competition remains as an important structuring force in habitats strongly influenced by disturbance. The conventional belief remains that the importance of competition decreases with increasing disturbance, but limited theory suggests otherwise. Using protist communities established in laboratory microcosms, we demonstrate that disturbance does not diminish the importance of competition. Interspecific competition significantly increased rates of species extinction over a broad disturbance gradient, and increasing disturbance intensities increased, rather than decreased, the tempo of competitive exclusion. This community-level pattern is linked to the species-level pattern that interspecific competition led to most frequent extinctions of each species at the highest level of disturbance that the species can tolerate. Consequently, despite a strong tradeoff between competitive ability and disturbance tolerance across the competing species, species diversity generally declined with disturbance. The consistent structuring role of competition throughout the disturbance gradient underscores the need to understand competitive interactions and their consequences even in highly disturbed habitats.

  10. A perspective on micro-evo-devo: progress and potential.

    PubMed

    Nunes, Maria D S; Arif, Saad; Schlötterer, Christian; McGregor, Alistair P

    2013-11-01

    The term "micro-evo-devo" refers to the combined study of the genetic and developmental bases of natural variation in populations and the evolutionary forces that have shaped this variation. It thus represents a synthesis of the fields of evolutionary developmental biology and population genetics. As has been pointed out by several others, this synthesis can provide insights into the evolution of organismal form and function that have not been possible within these individual disciplines separately. Despite a number of important successes in micro-evo-devo, however, it appears that evo devo and population genetics remain largely separate spheres of research, limiting their ability to address evolutionary questions. This also risks pushing contemporary evo devo to the fringes of evolutionary biology because it does not describe the causative molecular changes underlying evolution or the evolutionary forces involved. Here we reemphasize the theoretical and practical importance of micro-evo-devo as a strategy for understanding phenotypic evolution, review the key recent insights that it has provided, and present a perspective on both the potential and the remaining challenges of this exciting interdisciplinary field.

  11. Generation of Recombinant Polioviruses Harboring RNA Affinity Tags in the 5′ and 3′ Noncoding Regions of Genomic RNAs

    PubMed Central

    Flather, Dylan; Cathcart, Andrea L.; Cruz, Casey; Baggs, Eric; Ngo, Tuan; Gershon, Paul D.; Semler, Bert L.

    2016-01-01

    Despite being intensely studied for more than 50 years, a complete understanding of the enterovirus replication cycle remains elusive. Specifically, only a handful of cellular proteins have been shown to be involved in the RNA replication cycle of these viruses. In an effort to isolate and identify additional cellular proteins that function in enteroviral RNA replication, we have generated multiple recombinant polioviruses containing RNA affinity tags within the 3′ or 5′ noncoding region of the genome. These recombinant viruses retained RNA affinity sequences within the genome while remaining viable and infectious over multiple passages in cell culture. Further characterization of these viruses demonstrated that viral protein production and growth kinetics were unchanged or only slightly altered relative to wild type poliovirus. However, attempts to isolate these genetically-tagged viral genomes from infected cells have been hindered by high levels of co-purification of nonspecific proteins and the limited matrix-binding efficiency of RNA affinity sequences. Regardless, these recombinant viruses represent a step toward more thorough characterization of enterovirus ribonucleoprotein complexes involved in RNA replication. PMID:26861382

  12. Current thinking on genital herpes.

    PubMed

    Hofstetter, Annika M; Rosenthal, Susan L; Stanberry, Lawrence R

    2014-02-01

    Genital herpes has a high global prevalence and burden of disease. This manuscript highlights recent advances in our understanding of genital herpes simplex virus (HSV) infections. Studies demonstrate a changing epidemiological landscape with an increasing proportion of genital herpes cases associated with HSV type 1. There is also growing evidence that the majority of infected individuals exhibit frequent, brief shedding episodes that are most often asymptomatic, which likely contribute to high HSV transmission rates. Given this finding as well as readily available serological assays, some have proposed that routine HSV screening be performed; however, this remains controversial and is not currently recommended. Host immune responses, particularly local CD4 and CD8 T cell activity, are crucial for HSV control and clearance following initial infection, during latency and after reactivation. Prior HSV immunity may also afford partial protection against HSV reinfection and disease. Although HSV vaccine trials have been disappointing to date and existing antiviral medications are limited, novel prophylactic and therapeutic modalities are currently in development. Although much remains unknown about genital herpes, improved knowledge of HSV epidemiology, pathogenesis and host immunity may help guide new strategies for disease prevention and control.

  13. Strong underwater adhesives made by self-assembling multi-protein nanofibres.

    PubMed

    Zhong, Chao; Gurry, Thomas; Cheng, Allen A; Downey, Jordan; Deng, Zhengtao; Stultz, Collin M; Lu, Timothy K

    2014-10-01

    Many natural underwater adhesives harness hierarchically assembled amyloid nanostructures to achieve strong and robust interfacial adhesion under dynamic and turbulent environments. Despite recent advances, our understanding of the molecular design, self-assembly and structure-function relationships of these natural amyloid fibres remains limited. Thus, designing biomimetic amyloid-based adhesives remains challenging. Here, we report strong and multi-functional underwater adhesives obtained from fusing mussel foot proteins (Mfps) of Mytilus galloprovincialis with CsgA proteins, the major subunit of Escherichia coli amyloid curli fibres. These hybrid molecular materials hierarchically self-assemble into higher-order structures, in which, according to molecular dynamics simulations, disordered adhesive Mfp domains are exposed on the exterior of amyloid cores formed by CsgA. Our fibres have an underwater adhesion energy approaching 20.9 mJ m(-2), which is 1.5 times greater than the maximum of bio-inspired and bio-derived protein-based underwater adhesives reported thus far. Moreover, they outperform Mfps or curli fibres taken on their own and exhibit better tolerance to auto-oxidation than Mfps at pH ≥ 7.0.

  14. Acute graft-versus-host disease: a bench-to-bedside update.

    PubMed

    Holtan, Shernan G; Pasquini, Marcelo; Weisdorf, Daniel J

    2014-07-17

    Over the past 5 years, many novel approaches to early diagnosis, prevention, and treatment of acute graft-versus-host disease (aGVHD) have been translated from the bench to the bedside. In this review, we highlight recent discoveries in the context of current aGVHD care. The most significant innovations that have already reached the clinic are prophylaxis strategies based upon a refinement of our understanding of key sensors, effectors, suppressors of the immune alloreactive response, and the resultant tissue damage from the aGVHD inflammatory cascade. In the near future, aGVHD prevention and treatment will likely involve multiple modalities, including small molecules regulating immunologic checkpoints, enhancement of suppressor cytokines and cellular subsets, modulation of the microbiota, graft manipulation, and other donor-based prophylaxis strategies. Despite long-term efforts, major challenges in treatment of established aGVHD still remain. Resolution of inflammation and facilitation of rapid immune reconstitution in those with only a limited response to corticosteroids is a research arena that remains rife with opportunity and urgent clinical need. © 2014 by The American Society of Hematology.

  15. Rapid trench initiated recrystallization and stagnation in narrow Cu interconnect lines

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

    O'Brien, Brendan B.; Rizzolo, Michael; Prestowitz, Luke C.

    2015-10-26

    Understanding and ultimately controlling the self-annealing of Cu in narrow interconnect lines has remained a top priority in order to continue down-scaling of back-end of the line interconnects. Recently, it was hypothesized that a bottom-up microstructural transformation process in narrow interconnect features competes with the surface-initiated overburden transformation. Here, a set of transmission electron microscopy images which captures the grain coarsening process in 48 nm lines in a time resolved manner is presented, supporting such a process. Grain size measurements taken from these images have demonstrated that the Cu microstructural transformation in 48 nm interconnect lines stagnates after only 1.5 h atmore » room temperature. This stubborn metastable structure remains stagnant, even after aggressive elevated temperature anneals, suggesting that a limited internal energy source such as dislocation content is driving the transformation. As indicated by the extremely low defect density found in 48 nm trenches, a rapid recrystallization process driven by annihilation of defects in the trenches appears to give way to a metastable microstructure in the trenches.« less

  16. "You Have the Right to Remain Silent." Two Case Studies in Forensic Linguistics Involving Spanish Speaking Suspects.

    ERIC Educational Resources Information Center

    Perissinotto, Giorgio

    Two case studies involving possible violations of the rights of Spanish speaking criminal suspects are presented. In cases where suspects do not understand English, the Miranda warnings regarding the right to remain silent must be delivered in their native language and in a way that is understandable to the suspects. In the two cases involving…

  17. Molecular, Cellular and Pharmaceutical Aspects of Biomaterials in Dentistry and Oral and Maxillofacial Surgery. An Internationalization of Higher Education and Research Perspective.

    PubMed

    Wisniewska, Lidia M; Dohan Ehrenfest, David M; Galindo-Moreno, Pablo; Segovia, Jesus D; Inchingolo, Francesco; Wang, Hom-Lay; Fernandes-Cruz, Manuel

    2017-01-01

    In dentistry and oral and maxillofacial surgery, the development of implantable biomaterials and the understanding of their molecular, cellular and pharmaceutical aspects are currently major fields of research and education, with a considerable impact on the daily clinical practice and the evolution of therapeutic strategies. In the era of globalized economy of knowledge and science, this scientific domain needs the development of global cooperation and a paradigm evolution in the organizational culture of the dental sciences and related dental industry. Despite political pressure and theoretical efforts, the internationalization of higher education and research today in dentistry and biomaterials remains in general quite superficial and mostly dependent on the efforts of a few leaders of internationalization working through their personal networks, as it was assessed through the FAST scores (Fast Assessment Screening Test) calculated in various dental schools and groups worldwide through the ISAIAS program (Intercultural Sensitivity Academic Index &Advanced Standards). Cooperation in a multipolar multicultural community requires the development of strong intercultural competences, and this process remains limited in most institutions. These limits of international scientific cooperation can be observed through different markers, particularly the difficult and limited production of ISO standards (International Organization for Standardization) and the relatively low SCIENTI scores (Scientific Cooperation Internationalization Effort &Network Test &Index) of the specialized dental literature, particularly in comparison to the most significant medical literature. However, as an analytical tool to assess the scientific international cooperation effort between fields and periods, the SCIENTI screening system also highlighted a significant increase of the internationalization effort in the last years in the best dental biomaterials publications. Finally, an internationalization of higher education and research perspective is a very important approach to assess the evolution of the dental biomaterial science and highlights very clearly the future endeavors of this field, particularly the impact and interferences of private entities and companies in the development of this corpus of knowledge. It also reveals that the concept of independent not-for-profit Cooperation Internationalization Effort Literature (CIEL), in the various informal models that can be found worldwide around diverse leaderships, is the best perspective for a better science and understanding of molecular, cellular and pharmaceutical aspects of biomaterials in dentistry and oral and maxillofacial surgery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Abandoned babies and absent policies.

    PubMed

    Mueller, Joanne; Sherr, Lorraine

    2009-12-01

    Although infant abandonment is a historical problem, we know remarkably little about the conditions or effects of abandonment to guide evidence driven policies. This paper briefly reviews the existing international evidence base with reference to potential mental health considerations before mapping current UK guidelines and procedures, and available incidence data. Limitations arising from these findings are discussed with reference to international practice, and interpreted in terms of future pathways for UK policy. A systematic approach was utilized to gather available data on policy information and statistics on abandoned babies in the UK. A review of the limited literature indicates that baby abandonment continues to occur, with potentially wide-ranging mental health ramifications for those involved. However, research into such consequences is lacking, and evidence with which to understand risk factors or motives for abandonment is scarce. International approaches to the issue remain controversial with outcomes unclear. Our systematic search identified that no specific UK policy relating to baby abandonment exists, either nationally or institutionally. This is compounded by a lack of accurate of UK abandonment statistics. Data that does exist is not comprehensive and sources are incompatible, resulting in an ambiguous picture of UK baby abandonment. Available literature indicates an absence of clear provision, policy and research on baby abandonment. Based on current understanding of maternal and child mental health issues likely to be involved in abandonment, existing UK strategy could be easily adapted to avoid the 'learning from scratch' approach. National policies on recording and handling of baby abandonments are urgently needed, and future efforts should be concentrated on establishing clear data collection frameworks to inform understanding, guide competent practice and enable successfully targeted interventions.

  19. On the use of plant emitted volatile organic compounds for atmospheric chemistry simulation experiments

    NASA Astrophysics Data System (ADS)

    Kiendler-Scharr, A.; Hohaus, T.; Yu, Z.; Tillmann, R.; Kuhn, U.; Andres, S.; Kaminski, M.; Wegener, R.; Novelli, A.; Fuchs, H.; Wahner, A.

    2015-12-01

    Biogenic volatile organic compounds (BVOC) contribute to about 90% of the emitted VOC globally with isoprene being one of the most abundant BVOC (Guenther 2002). Intensive efforts in studying and understanding the impact of BVOC on atmospheric chemistry were undertaken in the recent years. However many uncertainties remain, e.g. field studies have shown that in wooded areas measured OH reactivity can often not be explained by measured BVOC and their oxidation products (e.g. Noelscher et al. 2012). This discrepancy may be explained by either a lack of understanding of BVOC sources or insufficient understanding of BVOC oxidation mechanisms. Plants emit a complex VOC mixture containing likely many compounds which have not yet been measured or identified (Goldstein and Galbally 2007). A lack of understanding BVOC sources limits bottom-up estimates of secondary products of BVOC oxidation such as SOA. Similarly, the widespread oversimplification of atmospheric chemistry in simulation experiments, using single compound or simple BVOC mixtures to study atmospheric chemistry processes limit our ability to assess air quality and climate impacts of BVOC. We will present applications of the new extension PLUS (PLant chamber Unit for Simulation) to our atmosphere simulation chamber SAPHIR. PLUS is used to produce representative BVOC mixtures from direct plant emissions. We will report on the performance and characterization of the newly developed chamber. As an exemplary application, trees typical of a Boreal forest environment were used to compare OH reactivity as directly measured by LIF to the OH reactivity calculated from BVOC measured by GC-MS and PTRMS. The comparison was performed for both, primary emissions of trees without any influence of oxidizing agents and using different oxidation schemes. For the monoterpene emitters investigated here, we show that discrepancies between measured and calculated total OH reactivity increase with increasing degree of oxidation. Implications for field studies and needs for future research are discussed.

  20. Cholesterol complacency in Australia: time to revisit the basics of cardiovascular disease prevention.

    PubMed

    Carrington, Melinda J; Retegan, Claudia; Johnston, Colin I; Jennings, Garry L; Stewart, Simon

    2009-03-01

    Community awareness of the importance of hypercholesterolemia and the need for appropriate therapy is an important part of global efforts to reduce the population burden of cardiovascular disease. The aim of this study was to assess the knowledge and attitudes about cholesterol and to determine adherence to taking cholesterol-lowering medication among patients at high risk for cardiovascular events. In spite of the availability of lifestyle and medical treatments for lipid management, an estimated 50% of adult Australians (6.4 million) remain at risk for a cardiovascular-related event because they have total blood cholesterol levels which exceed recommended limits. It is within this context that a significant gap remains in meeting cholesterol goals, despite easy to meet targets with readily available therapeutic options. A two-page national self-report postal survey was conducted from August-October 2006. A total of 508 Australian adults previously treated for hypercholesterolemia were surveyed to determine their understanding about cholesterol and their adherence to treatment. The mean age of participants was 67 (SD 10) years (72% male). Many participants (72%) were at risk of a cardiovascular event based on a prior history and 18% had type II diabetes. Participants had been prescribed lipid-lowering therapy (94% statin therapy) for an average of 10 years and visited their general practitioner on average three times per year. For those who knew their most recent cholesterol reading (67%), the total cholesterol was on average 4.5 (SD 1.1) mmol/l. This level was above the recommended limits for 40% of participants. Overall, 85% of participants reported knowing that there was high- and low-density lipoprotein forms of cholesterol, but only 56% and 38%, respectively, said that they understood or showed signs of clearly understanding the different types of cholesterol when their knowledge was assessed further. On the whole, therefore, participants had a limited understanding about cholesterol and its potential impact on cardiovascular events. Moreover, 25% of participants admitted to being non-compliant in taking their medication and only 51% correctly identified modifiable risk factors as most important for heart disease. Encouragingly, despite 85% of participants finding lifestyle changes challenging, most still identified their potential benefits. This study highlights that there are many unresolved issues in relation to educating high-risk patients who regularly visit their general practitioner to learn about and optimise their cholesterol levels via appropriate treatment and monitoring. There is a need for urgent public education and management by individuals and the health community. Strategies to address 'cholesterol complacency', in the sense of a willingness to accept sub-optimal standards of cholesterol control at both the patient and healthcare system levels (general practitioners in particular), are urgently needed to truncate an anticipated rising tide of cardiovascular disease in Australia.

  1. 30 CFR 285.236 - If I have a limited lease, how long will my lease remain in effect?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... lease remain in effect? 285.236 Section 285.236 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION, AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE RENEWABLE ENERGY ALTERNATE USES OF EXISTING FACILITIES ON THE OUTER CONTINENTAL SHELF Issuance of OCS Renewable Energy Leases Commercial and Limited...

  2. Ecological limit functions relating fish community response to hydrologic departures of the ecological flow regime in the Tennessee River basin, United States

    USGS Publications Warehouse

    Knight, Rodney R.; Murphy, Jennifer C.; Wolfe, William J.; Saylor, Charles F.; Wales, Amy K.

    2014-01-01

    Ecological limit functions relating streamflow and aquatic ecosystems remain elusive despite decades of research. We investigated functional relationships between species richness and changes in streamflow characteristics at 662 fish sampling sites in the Tennessee River basin. Our approach included the following: (1) a brief summary of relevant literature on functional relations between fish and streamflow, (2) the development of ecological limit functions that describe the strongest discernible relationships between fish species richness and streamflow characteristics, (3) the evaluation of proposed definitions of hydrologic reference conditions, and (4) an investigation of the internal structures of wedge-shaped distributions underlying ecological limit functions.Twenty-one ecological limit functions were developed across three ecoregions that relate the species richness of 11 fish groups and departures from hydrologic reference conditions using multivariate and quantile regression methods. Each negatively sloped function is described using up to four streamflow characteristics expressed in terms of cumulative departure from hydrologic reference conditions. Negative slopes indicate increased departure results in decreased species richness.Sites with the highest measured fish species richness generally had near-reference hydrologic conditions for a given ecoregion. Hydrology did not generally differ between sites with the highest and lowest fish species richness, indicating that other environmental factors likely limit species richness at sites with reference hydrology.Use of ecological limit functions to make decisions regarding proposed hydrologic regime changes, although commonly presented as a management tool, is not as straightforward or informative as often assumed. We contend that statistical evaluation of the internal wedge structure below limit functions may provide a probabilistic understanding of how aquatic ecology is influenced by altered hydrology and may serve as the basis for evaluating the potential effect of proposed hydrologic changes.

  3. The sticky business of adhesion prevention in minimally invasive gynecologic surgery.

    PubMed

    Han, Esther S; Scheib, Stacey A; Patzkowsky, Kristin E; Simpson, Khara; Wang, Karen C

    2017-08-01

    The negative impact of postoperative adhesions has long been recognized, but available options for prevention remain limited. Minimally invasive surgery is associated with decreased adhesion formation due to meticulous dissection with gentile tissue handling, improved hemostasis, and limiting exposure to reactive foreign material; however, there is conflicting evidence on the clinical significance of adhesion-related disease when compared to open surgery. Laparoscopic surgery does not guarantee the prevention of adhesions because longer operative times and high insufflation pressure can promote adhesion formation. Adhesion barriers have been available since the 1980s, but uptake among surgeons remains low and there is no clear evidence that they reduce clinically significant outcomes such as chronic pain or infertility. In this article, we review the ongoing magnitude of adhesion-related complications in gynecologic surgery, currently available interventions and new research toward more effective adhesion prevention. Recent literature provides updated epidemiologic data and estimates of healthcare costs associated with adhesion-related complications. There have been important advances in our understanding of normal peritoneal healing and the pathophysiology of adhesions. Adhesion barriers continue to be tested for safety and effectiveness and new agents have shown promise in clinical studies. Finally, there are many experimental studies of new materials and pharmacologic and biologic prevention agents. There is great interest in new adhesion prevention technologies, but new agents are unlikely to be available for clinical use for many years. High-quality effectiveness and outcomes-related research is still needed.

  4. Ischaemic heart disease in women: are there sex differences in pathophysiology and risk factors? Position paper from the working group on coronary pathophysiology and microcirculation of the European Society of Cardiology.

    PubMed

    Vaccarino, Viola; Badimon, Lina; Corti, Roberto; de Wit, Cor; Dorobantu, Maria; Hall, Alistair; Koller, Akos; Marzilli, Mario; Pries, Axel; Bugiardini, Raffaele

    2011-04-01

    Cardiovascular disease (CVD) is the leading cause of death in women, and knowledge of the clinical consequences of atherosclerosis and CVD in women has grown tremendously over the past 20 years. Research efforts have increased and many reports on various aspects of ischaemic heart disease (IHD) in women have been published highlighting sex differences in pathophysiology, presentation, and treatment of IHD. Data, however, remain limited. A description of the state of the science, with recognition of the shortcomings of current data, is necessary to guide future research and move the field forward. In this report, we identify gaps in existing literature and make recommendations for future research. Women largely share similar cardiovascular risk factors for IHD with men; however, women with suspected or confirmed IHD have less coronary atherosclerosis than men, even though they are older and have more cardiovascular risk factors than men. Coronary endothelial dysfunction and microvascular disease have been proposed as important determinants in the aetiology and prognosis of IHD in women, but research is limited on whether sex differences in these mechanisms truly exist. Differences in the epidemiology of IHD between women and men remain largely unexplained, as we are still unable to explain why women are protected towards IHD until older age compared with men. Eventually, a better understanding of these processes and mechanisms may improve the prevention and the clinical management of IHD in women.

  5. Cancer and the 'other' noncommunicable chronic diseases in older people living with HIV/AIDS in resource-limited settings: a challenge to success.

    PubMed

    Hirschhorn, Lisa R; Kaaya, Sylvia F; Garrity, Philip S; Chopyak, Elena; Fawzi, Mary C S

    2012-07-31

    There is considerable research around the morbidity and mortality related to noncommunicable diseases (NCDs), particularly cardiovascular disease and diabetes, among people living with HIV/AIDS (PLWHA) in resource-richer settings. Less is known about the burden and appropriate management of NCDs, particularly 'other' NCDs including cancer, renal, pulmonary, neurocognitive and mental health conditions, among older PLWHA in resource-limited settings (RLSs). We undertook a literature review of these other NCDs to explore what is currently known about them and identify areas of further research. Systematic literature review of published manuscripts and selected conference abstracts and reports. Although there is growing recognition of the importance of these NCDs among the aging population of PLWHA in RLSs, significant gaps remain in understanding the epidemiology and risk factors among older PLWHA in these settings. Even more concerning is the limited available evidence for effective and feasible approaches to prevention, screening and treatment of these conditions. The burden of these NCDs is related to both the aging of the population of PLWHA and an increased risk due to HIV infection, other comorbidities associated with HIV infection or transmission risk and underlying risk factors in the general community. Results from resource-richer settings and RLSs highlight malignancies, neurocognitive and mental health as well as renal disease as the most significant challenges currently and likely to increase in the future. Although some lessons can be taken from the growing experience with NCDs in older PLWHA in resource-richer settings, additional research is needed to better understand their risk and impact and identify optimal models of care to effectively address this challenge in the areas where the majority of older PLWHA will be receiving care.

  6. Determinants of hospital nurse intention to remain employed: broadening our understanding

    PubMed Central

    Tourangeau, Ann E; Cummings, Greta; Cranley, Lisa A; Ferron, Era Mae; Harvey, Sarah

    2010-01-01

    Title Determinants of hospital nurse intention to remain employed: broadening ourunderstanding. Aim This paper is a report of a study to identify nurse reported determinants of intention to remain employed and to develop a model explaining determinants of hospital nurse intention to remain employed. Background A worsening shortage of nurses globally suggests that efforts must be made to promote retention of nurses. However, effective retention promotion strategies depend on understanding the factors influencing nurse retention. Methods A descriptive study using focus group methodology was implemented. Thirteen focus groups including 78 nurses were carried out in two Canadian provinces in 2007. Thematic analysis strategies were incorporated to analyse the data. Findings Eight thematic categories reflecting factors nurses described as influencing their intentions to remain employed emerged from focus groups: (1) relationships with co-workers, (2) condition of the work environment, (3) relationship with and support from one’s manager, (4) work rewards, (5) organizational support and practices, (6) physical and psychological responses to work, (7) patient relationships and other job content, and (8) external factors. A model of determinants of hospital nurse intention to remain employed is hypothesized. Conclusion Findings were both similar to and different from previous research. The overriding concept of job satisfaction was not found. Rather, nurse assessments of satisfaction within eight thematic categories were found to influence intentions to remain employed. Further testing of the hypothesized model is required to determine its global utility. Understanding determinants of intention to remain employed can lead to development of strategies that strengthen nurse retention. Incorporation of this knowledge in nurse education programmes is essential. PMID:20423434

  7. Transcriptional Orchestration of the Global Cellular Response of a Model Pennate Diatom to Diel Light Cycling under Iron Limitation.

    PubMed

    Smith, Sarah R; Gillard, Jeroen T F; Kustka, Adam B; McCrow, John P; Badger, Jonathan H; Zheng, Hong; New, Ashley M; Dupont, Chris L; Obata, Toshihiro; Fernie, Alisdair R; Allen, Andrew E

    2016-12-01

    Environmental fluctuations affect distribution, growth and abundance of diatoms in nature, with iron (Fe) availability playing a central role. Studies on the response of diatoms to low Fe have either utilized continuous (24 hr) illumination or sampled a single time of day, missing any temporal dynamics. We profiled the physiology, metabolite composition, and global transcripts of the pennate diatom Phaeodactylum tricornutum during steady-state growth at low, intermediate, and high levels of dissolved Fe over light:dark cycles, to better understand fundamental aspects of genetic control of physiological acclimation to growth under Fe-limitation. We greatly expand the catalog of genes involved in the low Fe response, highlighting the importance of intracellular trafficking in Fe-limited diatoms. P. tricornutum exhibited transcriptomic hallmarks of slowed growth leading to prolonged periods of cell division/silica deposition, which could impact biogeochemical carbon sequestration in Fe-limited regions. Light harvesting and ribosome biogenesis transcripts were generally reduced under low Fe while transcript levels for genes putatively involved in the acquisition and recycling of Fe were increased. We also noted shifts in expression towards increased synthesis and catabolism of branched chain amino acids in P. tricornutum grown at low Fe whereas expression of genes involved in central core metabolism were relatively unaffected, indicating that essential cellular function is protected. Beyond the response of P. tricornutum to low Fe, we observed major coordinated shifts in transcript control of primary and intermediate metabolism over light:dark cycles which contribute to a new view of the significance of distinctive diatom pathways, such as mitochondrial glycolysis and the ornithine-urea cycle. This study provides new insight into transcriptional modulation of diatom physiology and metabolism across light:dark cycles in response to Fe availability, providing mechanistic understanding for the ability of diatoms to remain metabolically poised to respond quickly to Fe input and revealing strategies underlying their ecological success.

  8. Transcriptional Orchestration of the Global Cellular Response of a Model Pennate Diatom to Diel Light Cycling under Iron Limitation

    PubMed Central

    McCrow, John P.; Badger, Jonathan H.; Zheng, Hong; New, Ashley M.; Dupont, Chris L.; Obata, Toshihiro; Fernie, Alisdair R.; Allen, Andrew E.

    2016-01-01

    Environmental fluctuations affect distribution, growth and abundance of diatoms in nature, with iron (Fe) availability playing a central role. Studies on the response of diatoms to low Fe have either utilized continuous (24 hr) illumination or sampled a single time of day, missing any temporal dynamics. We profiled the physiology, metabolite composition, and global transcripts of the pennate diatom Phaeodactylum tricornutum during steady-state growth at low, intermediate, and high levels of dissolved Fe over light:dark cycles, to better understand fundamental aspects of genetic control of physiological acclimation to growth under Fe-limitation. We greatly expand the catalog of genes involved in the low Fe response, highlighting the importance of intracellular trafficking in Fe-limited diatoms. P. tricornutum exhibited transcriptomic hallmarks of slowed growth leading to prolonged periods of cell division/silica deposition, which could impact biogeochemical carbon sequestration in Fe-limited regions. Light harvesting and ribosome biogenesis transcripts were generally reduced under low Fe while transcript levels for genes putatively involved in the acquisition and recycling of Fe were increased. We also noted shifts in expression towards increased synthesis and catabolism of branched chain amino acids in P. tricornutum grown at low Fe whereas expression of genes involved in central core metabolism were relatively unaffected, indicating that essential cellular function is protected. Beyond the response of P. tricornutum to low Fe, we observed major coordinated shifts in transcript control of primary and intermediate metabolism over light:dark cycles which contribute to a new view of the significance of distinctive diatom pathways, such as mitochondrial glycolysis and the ornithine-urea cycle. This study provides new insight into transcriptional modulation of diatom physiology and metabolism across light:dark cycles in response to Fe availability, providing mechanistic understanding for the ability of diatoms to remain metabolically poised to respond quickly to Fe input and revealing strategies underlying their ecological success. PMID:27973599

  9. Transcriptional Orchestration of the Global Cellular Response of a Model Pennate Diatom to Diel Light Cycling under Iron Limitation

    DOE PAGES

    Smith, Sarah R.; Gillard, Jeroen T. F.; Kustka, Adam B.; ...

    2016-12-14

    Environmental fluctuations affect distribution, growth and abundance of diatoms in nature, with iron (Fe) availability playing a central role. Studies on the response of diatoms to low Fe have either utilized continuous (24 hr) illumination or sampled a single time of day, missing any temporal dynamics. We profiled the physiology, metabolite composition, and global transcripts of the pennate diatom Phaeodactylum tricornutum during steady-state growth at low, intermediate, and high levels of dissolved Fe over light:dark cycles, to better understand fundamental aspects of genetic control of physiological acclimation to growth under Fe-limitation. We greatly expand the catalog of genes involved inmore » the low Fe response, highlighting the importance of intracellular trafficking in Fe-limited diatoms. P. tricornutum exhibited transcriptomic hallmarks of slowed growth leading to prolonged periods of cell division/silica deposition, which could impact biogeochemical carbon sequestration in Fe-limited regions. Light harvesting and ribosome biogenesis transcripts were generally reduced under low Fe while transcript levels for genes putatively involved in the acquisition and recycling of Fe were increased. We also noted shifts in expression towards increased synthesis and catabolism of branched chain amino acids in P. tricornutum grown at low Fe whereas expression of genes involved in central core metabolism were relatively unaffected, indicating that essential cellular function is protected. Beyond the response of P. tricornutum to low Fe, we observed major coordinated shifts in transcript control of primary and intermediate metabolism over light:dark cycles which contribute to a new view of the significance of distinctive diatom pathways, such as mitochondrial glycolysis and the ornithine-urea cycle. This study provides new insight into transcriptional modulation of diatom physiology and metabolism across light:dark cycles in response to Fe availability, providing mechanistic understanding for the ability of diatoms to remain metabolically poised to respond quickly to Fe input and revealing strategies underlying their ecological success.« less

  10. Thermoregulation in endotherms: physiological principles and ecological consequences.

    PubMed

    Rezende, Enrico L; Bacigalupe, Leonardo D

    2015-10-01

    In a seminal study published nearly 70 years ago, Scholander et al. (Biol Bull 99:259-271, 1950) employed Newton's law of cooling to describe how metabolic rates (MR) in birds and mammals vary predictably with ambient temperature (T a). Here, we explore the theoretical consequences of Newton's law of cooling and show that a thermoregulatory polygon provides an intuitively simple and yet useful description of thermoregulatory responses in endothermic organisms. This polygon encapsulates the region in which heat production and dissipation are in equilibrium and, therefore, the range of conditions in which thermoregulation is possible. Whereas the typical U-shaped curve describes the relationship between T a and MR at rest, thermoregulatory polygons expand this framework to incorporate the impact of activity, other behaviors and environmental conditions on thermoregulation and energy balance. We discuss how this framework can be employed to study the limits to effective thermoregulation and their ecological repercussions, allometric effects and residual variation in MR and thermal insulation, and how thermoregulatory requirements might constrain locomotor or reproductive performance (as proposed, for instance, by the heat dissipation limit theory). In many systems the limited empirical knowledge on how organismal traits may respond to environmental changes prevents physiological ecology from becoming a fully developed predictive science. In endotherms, however, we contend that the lack of theoretical developments that translate current physiological understanding into formal mechanistic models remains the main impediment to study the ecological and evolutionary repercussions of thermoregulation. In spite of the inherent limitations of Newton's law of cooling as an oversimplified description of the mechanics of heat transfer, we argue that understanding how systems that obey this approximation work can be enlightening on conceptual grounds and relevant as an analytical and predictive tool to study ecological phenomena. As such, the proposed approach may constitute a powerful tool to study the impact of thermoregulatory constraints on variables related to fitness, such as survival and reproductive output, and help elucidating how species will be affected by ongoing climate change.

  11. Transcriptional Orchestration of the Global Cellular Response of a Model Pennate Diatom to Diel Light Cycling under Iron Limitation

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

    Smith, Sarah R.; Gillard, Jeroen T. F.; Kustka, Adam B.

    Environmental fluctuations affect distribution, growth and abundance of diatoms in nature, with iron (Fe) availability playing a central role. Studies on the response of diatoms to low Fe have either utilized continuous (24 hr) illumination or sampled a single time of day, missing any temporal dynamics. We profiled the physiology, metabolite composition, and global transcripts of the pennate diatom Phaeodactylum tricornutum during steady-state growth at low, intermediate, and high levels of dissolved Fe over light:dark cycles, to better understand fundamental aspects of genetic control of physiological acclimation to growth under Fe-limitation. We greatly expand the catalog of genes involved inmore » the low Fe response, highlighting the importance of intracellular trafficking in Fe-limited diatoms. P. tricornutum exhibited transcriptomic hallmarks of slowed growth leading to prolonged periods of cell division/silica deposition, which could impact biogeochemical carbon sequestration in Fe-limited regions. Light harvesting and ribosome biogenesis transcripts were generally reduced under low Fe while transcript levels for genes putatively involved in the acquisition and recycling of Fe were increased. We also noted shifts in expression towards increased synthesis and catabolism of branched chain amino acids in P. tricornutum grown at low Fe whereas expression of genes involved in central core metabolism were relatively unaffected, indicating that essential cellular function is protected. Beyond the response of P. tricornutum to low Fe, we observed major coordinated shifts in transcript control of primary and intermediate metabolism over light:dark cycles which contribute to a new view of the significance of distinctive diatom pathways, such as mitochondrial glycolysis and the ornithine-urea cycle. This study provides new insight into transcriptional modulation of diatom physiology and metabolism across light:dark cycles in response to Fe availability, providing mechanistic understanding for the ability of diatoms to remain metabolically poised to respond quickly to Fe input and revealing strategies underlying their ecological success.« less

  12. Characterization of Heat-treated Clay Minerals in the Context of Nuclear Waste Disposal

    NASA Astrophysics Data System (ADS)

    Matteo, E. N.; Wang, Y.; Kruichak, J. N.; Mills, M. M.

    2015-12-01

    Clay minerals are likely candidates to aid in nuclear waste isolation due to their low permeability, favorable swelling properties, and high cation sorption capacities. Establishing the thermal limit for clay minerals in a nuclear waste repository is a potentially important component of repository design, as flexibility of the heat load within the repository can have a major impact on the selection of repository design. For example, the thermal limit plays a critical role in the time that waste packages would need to cool before being transferred to the repository. Understanding the chemical and physical changes, if any, that occur in clay minerals at various temperatures above the current thermal limit (of 100 °C) can enable decision-makers with information critical to evaluating the potential trade-offs of increasing the thermal limit within the repository. Most critical is gaining understanding of how varying thermal conditions in the repository will impact radionuclide sorption and transport in clay materials either as engineered barriers or as disposal media. A variety of repository-relevant clay minerals (illite, mixed layer illite/smectite, and montmorillonite), were heated for a range of temperatures between 100-1000 °C. These samples were characterized to determine surface area, mineralogical alteration, and cation exchange capacity (CEC). Our results show that for conditions up to 500 °C, no significant change occurs, so long as the clay mineral remains mineralogically intact. At temperatures above 500 °C, transformation of the layered silicates into silica phases leads to alteration that impacts important clay characteristics. 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 Nation Nuclear Security Administration under contract DE-AC04-94AL85000. SAND Number: SAND2015-6524 A

  13. Health Literacy and Communication Quality in Health Care Organizations

    PubMed Central

    Wynia, Matthew K.; Osborn, Chandra Y.

    2011-01-01

    The relationship between limited health literacy and poor health may be due to poor communication quality within health care delivery organizations. We explored the relationship between health literacy status and receiving patient-centered communication in clinics and hospitals serving communication-vulnerable patient populations. Thirteen health care organizations nationwide distributed a survey to 5,929 patients. All patients completed seven items assessing patient-centered communication. One third also completed three items assessing health literacy. The majority of patients had self-reported health literacy challenges, reporting problems learning about their medical condition because of difficulty understanding written information (53%), a lack of confidence in completing medical forms by themselves (61%), and needing someone to help them read hospital/clinic materials (57%). Logistic regression models showed that, after adjustment for patient demographic characteristics and health care organization type, patients with limited health literacy were 28–79% less likely than those with adequate health literacy to report their health care organization “always” provides patient-centered communication across seven communication items. Using a scaled composite of these items, limited health literacy remained associated with lower reported communication quality. These results suggest that improving communication quality in health care organizations might help to address the challenges facing patients with limited health literacy. They also highlight that efforts to address the needs of patients with limited health literacy should be sensitive to the range of communication challenges confronting these patients and their caregivers. PMID:20845197

  14. Students' Understanding of Limiting Behavior at a Point for Functions from [Set of Real Numbers][superscript 2] to [Set of Real Numbers

    ERIC Educational Resources Information Center

    Mamona-Downs, Joanna K.; Megalou, Foteini J.

    2013-01-01

    The aim of this paper is to examine students' understanding of the limiting behavior of a function from [set of real numbers][superscript 2] to [set of real numbers] at a point "P." This understanding depends on which definition is used for a limit. Several definitions are considered; two of these concern the notion of a neighborhood of "P", while…

  15. The Effects of Acute Cannabis Use on Nontraffic Injury Risk: Reviewing the Available Literature and Identifying Ways Forward

    PubMed Central

    Andreuccetti, Gabriel; Ye, Yu; Kang, Jaewook; Korcha, Rachael; Witbrodt, Jane A.; Carvalho, Heraclito B.; Cherpitel, Cheryl J.

    2018-01-01

    Recent evidence has indicated that cannabis use before driving is associated with a modest but increased risk for traffic-related injuries. However, the question of whether recent cannabis use is associated with a greater risk for other types of injuries remains unanswered. Aiming to understand better how acute cannabis use might affect the risk for all causes of injury, we have summarized the limited data available in the literature on the risk of non-traffic injuries associated with recent cannabis use. Very few studies were able to provide estimate risks for all injuries or injuries other than those related to road traffic injuries, with the limited evidence available showing mixed findings. The only significant risk found (in only one study) suggests an inverse association between all injuries and cannabis use. Study designs are limited, and the majority of studies have neither data on acute cannabis use among injured individuals nor a valid control group for estimating injury risk attributable to cannabis. In conclusion, studies of the association between cannabis and non-traffic injuries present several limitations, particularly regarding sampling strategies, injury risk assessment for different causes of injury, and a dose-response risk relationship with injury. Further studies, incorporating better design for different causes of injury and drug testing, are required to reach firmer conclusions on the association between cannabis use and non-traffic injury risk. PMID:29456273

  16. Mechanisms of Phosphorus Acquisition and Lipid Class Remodeling under P Limitation in a Marine Microalga1[OPEN

    PubMed Central

    Winge, Per; El Assimi, Aimen; Jouhet, Juliette; Vadstein, Olav

    2017-01-01

    Molecular mechanisms of phosphorus (P) limitation are of great interest for understanding algal production in aquatic ecosystems. Previous studies point to P limitation-induced changes in lipid composition. As, in microalgae, the molecular mechanisms of this specific P stress adaptation remain unresolved, we reveal a detailed phospholipid-recycling scheme in Nannochloropsis oceanica and describe important P acquisition genes based on highly corresponding transcriptome and lipidome data. Initial responses to P limitation showed increased expression of genes involved in P uptake and an expansion of the P substrate spectrum based on purple acid phosphatases. Increase in P trafficking displayed a rearrangement between compartments by supplying P to the chloroplast and carbon to the cytosol for lipid synthesis. We propose a novel phospholipid-recycling scheme for algae that leads to the rapid reduction of phospholipids and synthesis of the P-free lipid classes. P mobilization through membrane lipid degradation is mediated mainly by two glycerophosphoryldiester phosphodiesterases and three patatin-like phospholipases A on the transcriptome level. To compensate for low phospholipids in exponential growth, N. oceanica synthesized sulfoquinovosyldiacylglycerol and diacylglyceroltrimethylhomoserine. In this study, it was shown that an N. oceanica strain has a unique repertoire of genes that facilitate P acquisition and the degradation of phospholipids compared with other stramenopiles. The novel phospholipid-recycling scheme opens new avenues for metabolic engineering of lipid composition in algae. PMID:29051196

  17. Nitrogen Availability Dampens the Positive Impacts of CO2 Fertilization on Terrestrial Ecosystem Carbon and Water Cycles

    NASA Astrophysics Data System (ADS)

    He, Liming; Chen, Jing M.; Croft, Holly; Gonsamo, Alemu; Luo, Xiangzhong; Liu, Jane; Zheng, Ting; Liu, Ronggao; Liu, Yang

    2017-11-01

    The magnitude and variability of the terrestrial CO2 sink remain uncertain, partly due to limited global information on ecosystem nitrogen (N) and its cycle. Without N constraint in ecosystem models, the simulated benefits from CO2 fertilization and CO2-induced increases in water use efficiency (WUE) may be overestimated. In this study, satellite observations of a relative measure of chlorophyll content are used as a proxy for leaf photosynthetic N content globally for 2003-2011. Global gross primary productivity (GPP) and evapotranspiration are estimated under elevated CO2 and N-constrained model scenarios. Results suggest that the rate of global GPP increase is overestimated by 85% during 2000-2015 without N limitation. This limitation is found to occur in many tropical and boreal forests, where a negative leaf N trend indicates a reduction in photosynthetic capacity, thereby suppressing the positive vegetation response to enhanced CO2 fertilization. Based on our carbon-water coupled simulations, enhanced CO2 concentration decreased stomatal conductance and hence increased WUE by 10% globally over the 1982 to 2015 time frame. Due to increased anthropogenic N application, GPP in croplands continues to grow and offset the weak negative trend in forests due to N limitation. Our results also show that the improved WUE is unlikely to ease regional droughts in croplands because of increases in evapotranspiration, which are associated with the enhanced GPP. Although the N limitation on GPP increase is large, its associated confidence interval is still wide, suggesting an urgent need for better understanding and quantification of N limitation from satellite observations.

  18. The Effects of Sooting and Radiation on Droplet Combustion

    NASA Technical Reports Server (NTRS)

    Lee, Kyeong-Ook; Manzello, Samuel L.; Choi, Mun Young

    1997-01-01

    The burning of liquid hydrocarbon fuels accounts for a significant portion of global energy production. With predicted future increases in demand and limited reserves of hydrocarbon fuel, it is important to maximize the efficiency of all processes that involve conversion of fuel. With the exception of unwanted fires, most applications involve introduction of liquid fuels into an oxidizing environment in the form of sprays which are comprised of groups of individual droplets. Therefore, tremendous benefits can result from a better understanding of spray combustion processes. Yet, theoretical developments and experimental measurements of spray combustion remains a daunting task due to the complex coupling of a turbulent, two-phase flow with phase change and chemical reactions. However, it is recognized that individual droplet behavior (including ignition, evaporation and combustion) is a necessary component for laying the foundation for a better understanding of spray processes. Droplet combustion is also an ideal problem for gaining a better understanding of non-premixed flames. Under the idealized situation producing spherically-symmetric flames (produced under conditions of reduced natural and forced convection), it represents the simplest geometry in which to formulate and solve the governing equations of mass, species and heat transfer for a chemically reacting two phase flow with phase change. The importance of this topic has promoted extensive theoretical investigations for more than 40 years.

  19. Adolescent drivers: a developmental perspective on risk, proficiency, and safety.

    PubMed

    Keating, Daniel P; Halpern-Felsher, Bonnie L

    2008-09-01

    Despite considerable improvement in the rates of crashes, injuries, and fatalities among adolescent drivers, attributable in part to effective interventions such as graduated driver licensing, these rates and their associated health risks remain unacceptably high. To understand the sources of risky driving among teens, as well as to identify potential avenues for further advances in prevention, this article presents a review of the relevant features of contemporary research on adolescent development. Current research offers significant advances in the understanding of the sources of safe driving, proficient driving, and risky driving among adolescents. This multifaceted perspective--as opposed to simple categorization of good versus bad driving--provides new opportunities for using insights on adolescent development to enhance prevention. Drawing on recent work on adolescent physical, neural, and cognitive development, we argue for approaches to prevention that recognize both the strengths and the limitations of adolescent drivers, with particular attention to the acquisition of expertise, regulatory competence, and self-regulation in the context of perceived risk. This understanding of adolescent development spotlights the provision of appropriate and effective scaffolding, utilizing the contexts of importance to adolescents--parents, peers, and the broader culture of driving--to support safe driving and to manage the inherent risks in learning to do so.

  20. Marine Protists Are Not Just Big Bacteria.

    PubMed

    Keeling, Patrick J; Campo, Javier Del

    2017-06-05

    The study of marine microbial ecology has been completely transformed by molecular and genomic data: after centuries of relative neglect, genomics has revealed the surprising extent of microbial diversity and how microbial processes transform ocean and global ecosystems. But the revolution is not complete: major gaps in our understanding remain, and one obvious example is that microbial eukaryotes, or protists, are still largely neglected. Here we examine various ways in which protists might be better integrated into models of marine microbial ecology, what challenges this will present, and why understanding the limitations of our tools is a significant concern. In part this is a technical challenge - eukaryotic genomes are more difficult to characterize - but eukaryotic adaptations are also more dependent on morphology and behaviour than they are on the metabolic diversity that typifies bacteria, and these cannot be inferred from genomic data as readily as metabolism can be. We therefore cannot simply follow in the methodological footsteps of bacterial ecology and hope for similar success. Understanding microbial eukaryotes will require different approaches, including greater emphasis on taxonomically and trophically diverse model systems. Molecular sequencing will continue to play a role, and advances in environmental sequence tag studies and single-cell methods for genomic and transcriptomics offer particular promise. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Communicating the promise, risks, and ethics of large-scale, open space microbiome and metagenome research.

    PubMed

    Shamarina, Daria; Stoyantcheva, Iana; Mason, Christopher E; Bibby, Kyle; Elhaik, Eran

    2017-10-04

    The public commonly associates microorganisms with pathogens. This suspicion of microorganisms is understandable, as historically microorganisms have killed more humans than any other agent while remaining largely unknown until the late seventeenth century with the works of van Leeuwenhoek and Kircher. Despite our improved understanding regarding microorganisms, the general public are apt to think of diseases rather than of the majority of harmless or beneficial species that inhabit our bodies and the built and natural environment. As long as microbiome research was confined to labs, the public's exposure to microbiology was limited. The recent launch of global microbiome surveys, such as the Earth Microbiome Project and MetaSUB (Metagenomics and Metadesign of Subways and Urban Biomes) project, has raised ethical, financial, feasibility, and sustainability concerns as to the public's level of understanding and potential reaction to the findings, which, done improperly, risk negative implications for ongoing and future investigations, but done correctly, can facilitate a new vision of "smart cities." To facilitate improved future research, we describe here the major concerns that our discussions with ethics committees, community leaders, and government officials have raised, and we expound on how to address them. We further discuss ethical considerations of microbiome surveys and provide practical recommendations for public engagement.

  2. Thermal barriers constrain microbial elevational range size via climate variability.

    PubMed

    Wang, Jianjun; Soininen, Janne

    2017-08-01

    Range size is invariably limited and understanding range size variation is an important objective in ecology. However, microbial range size across geographical gradients remains understudied, especially on mountainsides. Here, the patterns of range size of stream microbes (i.e., bacteria and diatoms) and macroorganisms (i.e., macroinvertebrates) along elevational gradients in Asia and Europe were examined. In bacteria, elevational range size showed non-significant phylogenetic signals. In all taxa, there was a positive relationship between niche breadth and species elevational range size, driven by local environmental and climatic variables. No taxa followed the elevational Rapoport's rule. Climate variability explained the most variation in microbial mean elevational range size, whereas local environmental variables were more important for macroinvertebrates. Seasonal and annual climate variation showed negative effects, while daily climate variation had positive effects on community mean elevational range size for all taxa. The negative correlation between range size and species richness suggests that understanding the drivers of range is key for revealing the processes underlying diversity. The results advance the understanding of microbial species thermal barriers by revealing the importance of seasonal and diurnal climate variation, and highlight that aquatic and terrestrial biota may differ in their response to short- and long-term climate variability. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  3. Developing a general conceptual framework for avian conservation science

    USGS Publications Warehouse

    Sauer, J.R.

    2003-01-01

    Avian conservation science in North America has produced a variety of monitoring programs designed to provide information on population status of birds. Waterfowl surveys provide population estimates for breeding ducks over most of the continent, the North American Breeding Bird Survey (BBS) provides indexes to population change for >400 breeding bird species, and many other surveys exist that index bird populations at a variety of scales and seasons. However, many fundamental questions about bird population change remain unanswered. I suggest that analyses of monitoring data provide limited understanding of causes of population change, and that the declining species paradigm (Caughley 1994) is sometimes an inefficient approach to increasing our understanding of causes of population change. In North America, the North American Bird Conservation Initiative (NABCI) provides an opportunity to implement alternative approaches that use management, modeling of population responses to management, and monitoring in combination to increase our understanding of bird populations. In adaptive resources management, modeling provides predictions about consequences of management, and monitoring data allow us to assess the population consequences of management. In this framework, alternative hypotheses about response of populations to management can be evaluated by formulating a series of models with differing structure, and management and monitoring provide information about which model best predicts population response.

  4. Hydrologic sensitivity of headwater catchments to climate and landscape variability

    NASA Astrophysics Data System (ADS)

    Kelleher, Christa; Wagener, Thorsten; McGlynn, Brian; Nippgen, Fabian; Jencso, Kelsey

    2013-04-01

    Headwater streams cumulatively represent an extensive portion of the United States stream network, yet remain largely unmonitored and unmapped. As such, we have limited understanding of how these systems will respond to change, knowledge that is important for preserving these unique ecosystems, the services they provide, and the biodiversity they support. We compare responses across five adjacent headwater catchments located in Tenderfoot Creek Experimental Forest in Montana, USA, to understand how local differences may affect the sensitivity of headwaters to change. We utilize global, variance-based sensitivity analysis to understand which aspects of the physical system (e.g., vegetation, topography, geology) control the variability in hydrologic behavior across these basins, and how this varies as a function of time (and therefore climate). Basin fluxes and storages, including evapotranspiration, snow water equivalent and melt, soil moisture and streamflow, are simulated using the Distributed Hydrology-Vegetation-Soil Model (DHSVM). Sensitivity analysis is applied to quantify the importance of different physical parameters to the spatial and temporal variability of different water balance components, allowing us to map similarities and differences in these controls through space and time. Our results show how catchment influences on fluxes vary across seasons (thus providing insight into transferability of knowledge in time), and how they vary across catchments with different physical characteristics (providing insight into transferability in space).

  5. Transcriptomic Crosstalk between Fungal Invasive Pathogens and Their Host Cells: Opportunities and Challenges for Next-Generation Sequencing Methods

    PubMed Central

    Enguita, Francisco J.; Costa, Marina C.; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José; Leitão, Ana Lúcia

    2016-01-01

    Fungal invasive infections are an increasing health problem. The intrinsic complexity of pathogenic fungi and the unmet clinical need for new and more effective treatments requires a detailed knowledge of the infection process. During infection, fungal pathogens are able to trigger a specific transcriptional program in their host cells. The detailed knowledge of this transcriptional program will allow for a better understanding of the infection process and consequently will help in the future design of more efficient therapeutic strategies. Simultaneous transcriptomic studies of pathogen and host by high-throughput sequencing (dual RNA-seq) is an unbiased protocol to understand the intricate regulatory networks underlying the infectious process. This protocol is starting to be applied to the study of the interactions between fungal pathogens and their hosts. To date, our knowledge of the molecular basis of infection for fungal pathogens is still very limited, and the putative role of regulatory players such as non-coding RNAs or epigenetic factors remains elusive. The wider application of high-throughput transcriptomics in the near future will help to understand the fungal mechanisms for colonization and survival, as well as to characterize the molecular responses of the host cell against a fungal infection. PMID:29376924

  6. What Is in a Name? How Biomedical Language May Derail Patient Understanding of Hypertension.

    PubMed

    Bokhour, Barbara G; Kressin, Nancy R

    2015-07-01

    Despite major advances in treating hypertension, >50% of all individuals diagnosed with the condition remain in poor control. A fundamental issue may be that patients may not fully understand the meaning of the term hypertension or its cause, leading to poor adherence to medications and limiting other effective self-management behaviors. We posit that the word hypertension itself may contribute to these misunderstandings, particularly in regards to the role of stress in causing hypertension, which thus suggests stress management as a primary strategy for control. The word hypertension is often interpreted by patients to mean too much tension. In conjunction with cultural framings of stress causing high blood pressure, many patients turn to stress management to control their hypertension. The word hypertension can thus cause patients to think of it as more of a psychological than physiological condition, thus discounting the value of antihypertensive medications and interfering with medication adherence. We therefore suggest that clinicians reconsider the use of the term hypertension and the ways in which they explain the condition to patients. Reorienting the language to the more patient-centered term of high blood pressure may help patients better understand the condition and to more readily embrace the available efficacious therapies. © 2015 American Heart Association, Inc.

  7. Mechanical and Biological Interactions of Implants with the Brain and Their Impact on Implant Design

    PubMed Central

    Prodanov, Dimiter; Delbeke, Jean

    2016-01-01

    Neural prostheses have already a long history and yet the cochlear implant remains the only success story about a longterm sensory function restoration. On the other hand, neural implants for deep brain stimulation are gaining acceptance for variety of disorders including Parkinsons disease and obsessive-compulsive disorder. It is anticipated that the progress in the field has been hampered by a combination of technological and biological factors, such as the limited understanding of the longterm behavior of implants, unreliability of devices, biocompatibility of the implants among others. While the field's understanding of the cell biology of interactions at the biotic-abiotic interface has improved, relatively little attention has been paid on the mechanical factors (stress, strain), and hence on the geometry that can modulate it. This focused review summarizes the recent progress in the understanding of the mechanisms of mechanical interaction between the implants and the brain. The review gives an overview of the factors by which the implants interact acutely and chronically with the tissue: blood-brain barrier (BBB) breach, vascular damage, micromotions, diffusion etc. We propose some design constraints to be considered in future studies. Aspects of the chronic cell-implant interaction will be discussed in view of the chronic local inflammation and the ways of modulating it. PMID:26903786

  8. Development of low-cost technology for the next generation of high efficiency solar cells composed of earth abundant elements

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

    Agrawal, Rakesh

    2014-09-28

    The development of renewable, affordable, and environmentally conscious means of generating energy on a global scale represents a grand challenge of our time. Due to the “permanence” of radiation from the sun, solar energy promises to remain a viable and sustainable power source far into the future. Established single-junction photovoltaic technologies achieve high power conversion efficiencies (pce) near 20% but require complicated manufacturing processes that prohibit the marriage of large-scale throughput (e.g. on the GW scale), profitability, and quality control. Our approach to this problem begins with the synthesis of nanocrystals of semiconductor materials comprising earth abundant elements and characterizedmore » by material and optoelectronic properties ideal for photovoltaic applications, namely Cu2ZnSn(S,Se)4 (CZTSSe). Once synthesized, such nanocrystals are formulated into an ink, coated onto substrates, and processed into completed solar cells in such a way that enables scale-up to high throughput, roll-to-roll manufacturing processes. This project aimed to address the major limitation to CZTSSe solar cell pce’s – the low open-circuit voltage (Voc) reported throughout literature for devices comprised of this material. Throughout the project significant advancements have been made in fundamental understanding of the CZTSSe material and device limitations associated with this material system. Additionally, notable improvements have been made to our nanocrystal based processing technique to alleviate performance limitations due to the identified device limitations. Notably, (1) significant improvements have been made in reducing intra- and inter-nanoparticle heterogeneity, (2) improvements in device performance have been realized with novel cation substitution in Ge-alloyed CZTGeSSe absorbers, (3) systematic analysis of absorber sintering has been conducted to optimize the selenization process for large grain CZTSSe absorbers, (4) novel electrical characterization analysis techniques have been developed to identify significant limitations to traditional electrical characterization of CZTSSe devices, and (5) the developed electrical analysis techniques have been used to identify the role that band gap and electrostatic potential fluctuations have in limiting device performance for this material system. The device modeling and characterization of CZTSSe undertaken with this project have significant implications for the CZTSSe research community, as the identified limitations due to potential fluctuations are expected to be a performance limitation to high-efficiency CZTSSe devices fabricated from all current processing techniques. Additionally, improvements realized through enhanced absorber processing conditions to minimize nanoparticle and large-grain absorber heterogeneity are suggested to be beneficial processing improvements which should be applied to CZTSSe devices fabricated from all processing techniques. Ultimately, our research has indicated that improved performance for CZTSSe will be achieved through novel absorber processing which minimizes defect formation, elemental losses, secondary phase formation, and compositional uniformity in CZTSSe absorbers; we believe this novel absorber processing can be achieved through nanocrystal based processing of CZTSSe which is an active area of research at the conclusion of this award. While significant fundamental understanding of CZTSSe and the performance limitations associated with this material system, as well as notable improvements in the processing of nanocrystal based CZTSSe absorbers, have been achieved under this project, the limitation of two years of research funding towards our goals prevents further significant advancements directly identified through pce. improvements relative to those reported herein. As the characterization and modeling subtask of this project has been the main driving force for understanding device limitations, the conclusions of this analysis have just recently been applied to the processing of nanocrystal based CZTSSe absorbers -- with notable success. We expect the notable fundamental understanding of device limitations and absorber sintering achieved under this project will lead to significant improvements in device performance for CZTSSe devices in the near future for devices fabricated from a variety of processing techniques« less

  9. Novel Loci Underlie Natural Variation in Vitamin E Levels in Maize Grain[OPEN

    PubMed Central

    Diepenbrock, Christine H.; Kandianis, Catherine B.; Lipka, Alexander E.; Magallanes-Lundback, Maria; Vaillancourt, Brieanne; Cepela, Jason; Bradbury, Peter J.; Mateos-Hernandez, Maria; Hamilton, John; Owens, Brenda F.; Tiede, Tyler; Rocheford, Torbert

    2017-01-01

    Tocopherols, tocotrienols, and plastochromanols (collectively termed tocochromanols) are lipid-soluble antioxidants synthesized by all plants. Their dietary intake, primarily from seed oils, provides vitamin E and other health benefits. Tocochromanol biosynthesis has been dissected in the dicot Arabidopsis thaliana, which has green, photosynthetic seeds, but our understanding of tocochromanol accumulation in major crops, whose seeds are nonphotosynthetic, remains limited. To understand the genetic control of tocochromanols in grain, we conducted a joint linkage and genome-wide association study in the 5000-line U.S. maize (Zea mays) nested association mapping panel. Fifty-two quantitative trait loci for individual and total tocochromanols were identified, and of the 14 resolved to individual genes, six encode novel activities affecting tocochromanols in plants. These include two chlorophyll biosynthetic enzymes that explain the majority of tocopherol variation, which was not predicted given that, like most major cereal crops, maize grain is nonphotosynthetic. This comprehensive assessment of natural variation in vitamin E levels in maize establishes the foundation for improving tocochromanol and vitamin E content in seeds of maize and other major cereal crops. PMID:28970338

  10. Ticks and Tick-Borne Pathogens of the Caribbean: Current Understanding and Future Directions for More Comprehensive Surveillance.

    PubMed

    Gondard, Mathilde; Cabezas-Cruz, Alejandro; Charles, Roxanne A; Vayssier-Taussat, Muriel; Albina, Emmanuel; Moutailler, Sara

    2017-01-01

    Ticks are obligate hematophagous arthropods of significant importance to human and veterinary medicine. They transmit a vast array of pathogens, including bacteria, viruses, protozoa, and helminths. Most epidemiological data on ticks and tick-borne pathogens (TBPs) in the West Indies are limited to common livestock pathogens such as Ehrlichia ruminantium, Babesia spp. (i.e., B. bovis and B. bigemina ), and Anaplasma marginale , and less information is available on companion animal pathogens. Of note, human tick-borne diseases (TBDs) remain almost completely uncharacterized in the West Indies. Information on TBP presence in wildlife is also missing. Herein, we provide a comprehensive review of the ticks and TBPs affecting human and animal health in the Caribbean, and introduce the challenges associated with understanding TBD epidemiology and implementing successful TBD management in this region. In particular, we stress the need for innovative and versatile surveillance tools using high-throughput pathogen detection (e.g., high-throughput real-time microfluidic PCR). The use of such tools in large epidemiological surveys will likely improve TBD prevention and control programs in the Caribbean.

  11. Epigenetic mechanisms in cerebral ischemia

    PubMed Central

    Schweizer, Sophie; Meisel, Andreas; Märschenz, Stefanie

    2013-01-01

    Treatment efficacy for ischemic stroke represents a major challenge. Despite fundamental advances in the understanding of stroke etiology, therapeutic options to improve functional recovery remain limited. However, growing knowledge in the field of epigenetics has dramatically changed our understanding of gene regulation in the last few decades. According to the knowledge gained from animal models, the manipulation of epigenetic players emerges as a highly promising possibility to target diverse neurologic pathologies, including ischemia. By altering transcriptional regulation, epigenetic modifiers can exert influence on all known pathways involved in the complex course of ischemic disease development. Beneficial transcriptional effects range from attenuation of cell death, suppression of inflammatory processes, and enhanced blood flow, to the stimulation of repair mechanisms and increased plasticity. Most striking are the results obtained from pharmacological inhibition of histone deacetylation in animal models of stroke. Multiple studies suggest high remedial qualities even upon late administration of histone deacetylase inhibitors (HDACi). In this review, the role of epigenetic mechanisms, including histone modifications as well as DNA methylation, is discussed in the context of known ischemic pathways of damage, protection, and regeneration. PMID:23756691

  12. On the Unreasonable Effectiveness of post-Newtonian Theory in Gravitational-Wave Physics

    ScienceCinema

    Will, Clifford M.

    2017-12-22

    The first indirect detection of gravitational waves involved a binary system of neutron stars.  In the future, the first direct detection may also involve binary systems -- inspiralling and merging binary neutron stars or black holes. This means that it is essential to understand in full detail the two-body system in general relativity, a notoriously difficult problem with a long history. Post-Newtonian approximation methods are thought to work only under slow motion and weak field conditions, while numerical solutions of Einstein's equations are thought to be limited to the final merger phase.  Recent results have shown that post-Newtonian approximations seem to remain unreasonably valid well into the relativistic regime, while advances in numerical relativity now permit solutions for numerous orbits before merger.  It is now possible to envision linking post-Newtonian theory and numerical relativity to obtain a complete "solution" of the general relativistic two-body problem.  These solutions will play a central role in detecting and understanding gravitational wave signals received by interferometric observatories on Earth and in space.

  13. Sampling methods for recovery of human enteric viruses from environmental surfaces.

    PubMed

    Turnage, Nicole L; Gibson, Kristen E

    2017-10-01

    Acute gastroenteritis causes the second highest infectious disease burden worldwide. Human enteric viruses have been identified as leading causative agents of acute gastroenteritis as well as foodborne illnesses in the U.S. and are generally transmitted by fecal-oral contamination. There is growing evidence of transmission occurring via contaminated fomite including food contact surfaces. Additionally, human enteric viruses have been shown to remain infectious on fomites over prolonged periods of time. To better understand viral persistence, there is a need for more studies to investigate this phenomenon. Therefore, optimization of surface sampling methods is essential to aid in understanding environmental contamination to ensure proper preventative measures are being applied. In general, surface sampling studies are limited and highly variable among recovery efficiencies and research parameters used (e.g., virus type/density, surface type, elution buffers, tools). This review aims to discuss the various factors impacting surface sampling of viruses from fomites and to explore how researchers could move towards a more sensitive and standard sampling method. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Tissue-enriched expression profiles in Aedes aegypti identify hemocyte-specific transcriptome responses to infection

    PubMed Central

    Choi, Young-Jun; Fuchs, Jeremy F.; Mayhew, George F.; Yu, Helen E.; Christensen, Bruce M.

    2012-01-01

    Hemocytes are integral components of mosquito immune mechanisms such as phagocytosis, melanization, and production of antimicrobial peptides. However, our understanding of hemocyte-specific molecular processes and their contribution to shaping the host immune response remains limited. To better understand the immunophysiological features distinctive of hemocytes, we conducted genome-wide analysis of hemocyte-enriched transcripts, and examined how tissue-enriched expression patterns change with the immune status of the host. Our microarray data indicate that the hemocyte-enriched trascriptome is dynamic and context-dependent. Analysis of transcripts enriched after bacterial challenge in circulating hemocytes with respect to carcass added a dimension to evaluating infection-responsive genes and immune-related gene families. We resolved patterns of transcriptional change unique to hemocytes from those that are likely shared by other immune responsive tissues, and identified clusters of genes preferentially induced in hemocytes, likely reflecting their involvement in cell type specific functions. In addition, the study revealed conserved hemocyte-enriched molecular repertoires which might be implicated in core hemocyte function by cross-species meta-analysis of microarray expression data from Anopheles gambiae and Drosophila melanogaster. PMID:22796331

  15. Environmental contaminants of health-care origin: Exposure and potential effects in wildlife

    USGS Publications Warehouse

    Bean, Thomas; Rattner, Barnett A.

    2018-01-01

    A diverse range of fauna could be exposed to active pharmaceutical ingredients (APIs) via diet, dermal absorption or bioconcentration. Low level exposures of free-ranging wildlife to APIs has only been demonstrated for a few pathways (e.g., ingestion of fish in estuaries by piscivorous birds), and many remain hypothetical (e.g., ingestion of invertebrates in sludge amended fields by terrestrial vertebrates). Our understanding of API dose-response relationships in wildlife have only been assessed for endocrine disrupting compounds and a few veterinary therapeutics. Drug specific responses at various levels of biological organization are poorly characterized for nearly all wildlife species, and thus our understanding of risk is limited. There is interest in using a read-across approach to fill knowledge gaps for risk. This approach, using data collected in laboratory mammals and humans, would enable predictions for likelihood of adverse effects in wildlife. Given the great diversities in physiologies among species, a combination of in vivo, in vitro and in silico approaches will be required to fill the knowledge gaps for exposure, hazard and risk.

  16. Nasal polyps in patients with asthma: prevalence, impact, and management challenges

    PubMed Central

    Langdon, Cristobal; Mullol, Joaquim

    2016-01-01

    Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have coexisting asthma under the concept of “United Airway Disease”, being the combination of both diseases, which is one of the most challenging phenotypes to treat. Although clinicians have recognized this difficult-to-treat phenotype for many years, it remained poorly characterized. There is increasing epidemiological evidence linking chronic rhinosinusitis and asthma, but a good understanding of the pathophysiology and the combined management is still lacking. Bronchial asthma is more prevalent in patients who suffer chronic rhinosinusitis, while asthmatic patients have a greater prevalence of CRSwNP than patients without asthma. The effect of CRSwNP treatment, whether medical or surgical, in asthma is today less controversial after some studies have shown improvement of asthma after medical and/or surgical treatment of CRSwNP. However, direct comparisons between surgical and medical treatments are limited. Further randomized clinical trials are, however, still needed to better understand the management when both asthma and CRSwNP occur together. This review aims at summarizing the prevalence, impact, and management challenges regarding both asthma and CRSwNP. PMID:27042129

  17. Acceleration of High Energy Cosmic Rays in the Nonlinear Shock Precursor

    NASA Astrophysics Data System (ADS)

    Derzhinsky, F.; Diamond, P. H.; Malkov, M. A.

    2006-10-01

    The problem of understanding acceleration of very energetic cosmic rays to energies above the 'knee' in the spectrum at 10^15-10^16eV remains one of the great challenges in modern physics. Recently, we have proposed a new approach to understanding high energy acceleration, based on exploiting scattering of cosmic rays by inhomogenities in the compressive nonlinear shock precursor, rather than by scattering across the main shock, as is conventionally assumed. We extend that theory by proposing a mechanism for the generation of mesoscale magnetic fields (krg<1, where rg is the cosmic ray gyroradius). The mechanism is the decay or modulational instability of resonantly generated Alfven waves scattering off ambient density perturbations in the precursors. Such perturbations can be produced by Drury instability. This mechanism leads to the generation of longer wavelength Alfven waves, thus enabling the confinement of higher energy particles. A simplified version of the theory, cast in the form of a Fokker-Planck equation for the Alfven population, will also be presented. This process also limits field generation on rg scales.

  18. Why Human Papillomavirus Acute Infections Matter

    PubMed Central

    2017-01-01

    Most infections by human papillomaviruses (HPVs) are ‘acute’, that is non-persistent. Yet, for HPVs, as for many other oncoviruses, there is a striking gap between our detailed understanding of chronic infections and our limited data on the early stages of infection. Here we argue that studying HPV acute infections is necessary and timely. Focusing on early interactions will help explain why certain infections are cleared while others become chronic or latent. From a molecular perspective, descriptions of immune effectors and pro-inflammatory pathways during the initial stages of infections have the potential to lead to novel treatments or to improved handling algorithms. From a dynamical perspective, adopting concepts from spatial ecology, such as meta-populations or meta-communities, can help explain why HPV acute infections sometimes last for years. Furthermore, cervical cancer screening and vaccines impose novel iatrogenic pressures on HPVs, implying that anticipating any viral evolutionary response remains essential. Finally, hints at the associations between HPV acute infections and fertility deserve further investigation given their high, worldwide prevalence. Overall, understanding asymptomatic and benign infections may be instrumental in reducing HPV virulence. PMID:28994707

  19. A review of breast cancer survivorship issues from survivors' perspectives.

    PubMed

    Cho, Jihyoung; Jung, So-Youn; Lee, Jung Eun; Shim, Eun-Jung; Kim, Nam Hyoung; Kim, Zisun; Sohn, Guiyun; Youn, Hyun Jo; Kim, Ku Sang; Kim, Hanna; Lee, Jong Won; Lee, Min Hyuk

    2014-09-01

    Despite the fact that more breast cancer survivors are currently enjoying longer lifespans, there remains limited knowledge about the factors and issues that are of greatest significance for these survivors, particularly from their perspectives. This review was based on the concept that the topics addressed should focus on the perspectives of current survivors and should be extended to future modalities, which physicians will be able to use to gain a better understanding of the hidden needs of these patients. We intended to choose and review dimensions other than the pathology and the disease process that could have been overlooked during treatment. The eight topics upon which we focused included: delay of treatment and survival outcome; sexual well-being; concerns about childbearing; tailored follow-up; presence of a family history of breast cancer; diet and physical activity for survivors and their families; qualitative approach toward understanding of breast cancer survivorship, and; mobile health care for breast cancer survivors. Through this review, we aimed to examine the present clinical basis of the central issues noted from the survivors' perspectives and suggest a direction for future survivorship-related research.

  20. Time series modeling in traffic safety research.

    PubMed

    Lavrenz, Steven M; Vlahogianni, Eleni I; Gkritza, Konstantina; Ke, Yue

    2018-08-01

    The use of statistical models for analyzing traffic safety (crash) data has been well-established. However, time series techniques have traditionally been underrepresented in the corresponding literature, due to challenges in data collection, along with a limited knowledge of proper methodology. In recent years, new types of high-resolution traffic safety data, especially in measuring driver behavior, have made time series modeling techniques an increasingly salient topic of study. Yet there remains a dearth of information to guide analysts in their use. This paper provides an overview of the state of the art in using time series models in traffic safety research, and discusses some of the fundamental techniques and considerations in classic time series modeling. It also presents ongoing and future opportunities for expanding the use of time series models, and explores newer modeling techniques, including computational intelligence models, which hold promise in effectively handling ever-larger data sets. The information contained herein is meant to guide safety researchers in understanding this broad area of transportation data analysis, and provide a framework for understanding safety trends that can influence policy-making. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. In-Situ Quantification of the Interfacial Rheological Response of Bacterial Biofilms to Environmental Stimuli

    PubMed Central

    Rühs, Patrick A.; Böni, Lukas; Fuller, Gerald G.; Inglis, R. Fredrik; Fischer, Peter

    2013-01-01

    Understanding the numerous factors that can affect biofilm formation and stability remain poorly understood. One of the major limitations is the accurate measurement of biofilm stability and cohesiveness in real-time when exposed to changing environmental conditions. Here we present a novel method to measure biofilm strength: interfacial rheology. By culturing a range of bacterial biofilms on an air-liquid interface we were able to measure their viscoelastic growth profile during and after biofilm formation and subsequently alter growth conditions by adding surfactants or changing the nutrient composition of the growth medium. We found that different bacterial species had unique viscoelastic growth profiles, which was also highly dependent on the growth media used. We also found that we could reduce biofilm formation by the addition of surfactants or changing the pH, thereby altering the viscoelastic properties of the biofilm. Using this technique we were able to monitor changes in viscosity, elasticity and surface tension online, under constant and varying environmental conditions, thereby providing a complementary method to better understand the dynamics of both biofilm formation and dispersal. PMID:24244319

  2. Correlative nanoscale imaging of actin filaments and their complexes

    NASA Astrophysics Data System (ADS)

    Sharma, Shivani; Zhu, Huanqi; Grintsevich, Elena E.; Reisler, Emil; Gimzewski, James K.

    2013-06-01

    Actin remodeling is an area of interest in biology in which correlative microscopy can bring a new way to analyze protein complexes at the nanoscale. Advances in EM, X-ray diffraction, fluorescence, and single molecule techniques have provided a wealth of information about the modulation of the F-actin structure and its regulation by actin binding proteins (ABPs). Yet, there are technological limitations of these approaches to achieving quantitative molecular level information on the structural and biophysical changes resulting from ABPs interaction with F-actin. Fundamental questions about the actin structure and dynamics and how these determine the function of ABPs remain unanswered. Specifically, how local and long-range structural and conformational changes result in ABPs induced remodeling of F-actin needs to be addressed at the single filament level. Advanced, sensitive and accurate experimental tools for detailed understanding of ABP-actin interactions are much needed. This article discusses the current understanding of nanoscale structural and mechanical modulation of F-actin by ABPs at the single filament level using several correlative microscopic techniques, focusing mainly on results obtained by Atomic Force Microscopy (AFM) analysis of ABP-actin complexes.

  3. Pathways to psychosis in cannabis abuse.

    PubMed

    Shrivastava, Amresh; Johnston, Megan; Terpstra, Kristen; Bureau, Yves

    2015-04-01

    Cannabis has been implicated as a risk factor for the development of schizophrenia, but the exact biological mechanisms remain unclear. In this review, we attempt to understand the neurobiological pathways that link cannabis use to schizophrenia. This has been an area of great debate; despite similarities between cannabis users and schizophrenia patients, the evidence is not sufficient to establish cause-and-effect. There have been advances in the understanding of the mechanisms of cannabis dependence as well as the role of the cannabinoid system in the development of psychosis and schizophrenia. The neurobiological mechanisms associated with the development of psychosis and effects from cannabis use may be similar but remain elusive. In order to better understand these associations, this paper will show common neurobiological and neuroanatomical changes as well as common cognitive dysfunction in cannabis users and patients of schizophrenia. We conclude that epidemiologic evidence highlights potential causal links; however, neurobiological evidence for causality remains weak.

  4. Twelve-Month-Olds' Understanding of Intention Transfer through Communication

    PubMed Central

    Cheung, Him; Xiao, Wen; Lai, Ching Man

    2012-01-01

    Do infants understand that intention can be transferred through communication? We answered this question by examining 12-month-olds' looking times in a violation-of-expectation paradigm with two human agents. In familiarization, the non-acting agent spoke, clapped her hands, read aloud a book, or remained silent before the acting agent grasped one (the target) of two objects. During test only the non-actor remained, grasping either the target or distractor. The infants looked longer in the distractor than target condition, suggesting violation of expectation, only if the non-actor had spoken or clapped in familiarization. Because the non-actor never had grasped any of the objects in familiarization, the infants' expectation on her behavior could have developed from the understanding that her intention was transferred to the actor, who executed it by grasping the target in familiarization, via speaking and clapping as acts of communication (but not reading aloud and remaining silent). PMID:23029427

  5. Twelve-month-olds' understanding of intention transfer through communication.

    PubMed

    Cheung, Him; Xiao, Wen; Lai, Ching Man

    2012-01-01

    Do infants understand that intention can be transferred through communication? We answered this question by examining 12-month-olds' looking times in a violation-of-expectation paradigm with two human agents. In familiarization, the non-acting agent spoke, clapped her hands, read aloud a book, or remained silent before the acting agent grasped one (the target) of two objects. During test only the non-actor remained, grasping either the target or distractor. The infants looked longer in the distractor than target condition, suggesting violation of expectation, only if the non-actor had spoken or clapped in familiarization. Because the non-actor never had grasped any of the objects in familiarization, the infants' expectation on her behavior could have developed from the understanding that her intention was transferred to the actor, who executed it by grasping the target in familiarization, via speaking and clapping as acts of communication (but not reading aloud and remaining silent).

  6. Detecting and characterizing circular RNAs

    PubMed Central

    Jeck, William R.; Sharpless, Norman E.

    2014-01-01

    Circular RNA transcripts were first identified in the early 1990s but knowledge of these species has remained limited, as their study has been difficult through traditional methods of RNA analysis. Now, novel bioinformatic approaches coupled with biochemical enrichment strategies and deep sequencing have allowed comprehensive studies of circular RNA species. Recent studies have revealed thousands of endogenous circular RNAs (circRNAs) in mammalian cells, some of which are highly abundant and evolutionarily conserved. Evidence is emerging that some circRNAs might regulate microRNA (miRNA) function, and roles in transcriptional control have also been suggested. Therefore, study of this class of non-coding RNAs has potential implications for therapeutic and research applications. We believe the key future challenge to the field will be to understand the regulation and function of these unusual molecules. PMID:24811520

  7. A study of EWOD-driven droplets by PIV investigation.

    PubMed

    Lu, Hsiang-Wei; Bottausci, Frederic; Fowler, Jesse D; Bertozzi, Andrea L; Meinhart, Carl; Kim, Chang-Jin C J

    2008-03-01

    Despite the recent interest in droplet-based microfluidics using electrowetting-on-dielectric (EWOD), fundamental understanding of the fluid dynamics remains limited to two-dimensional (2D) reduction of the Navier-Stokes equation. Experimental data are in dire need to verify the predictions and advance the field. We report an investigation of the flow inside droplets actuated by EWOD in air using micro particle image velocimetry (micro-PIV). Using the continuity equation, we reconstruct the 3D velocity field from the 2D PIV experimental data. We present some fundamental findings and build valuable insights that will help design sophisticated EWOD microfluidic devices. For example, the results confirm that efficient mixing in a droplet may be achieved by moving the droplet along an irreversible pattern that breaks the symmetry of the two circulating inner flows.

  8. Ferret models of viral pathogenesis.

    PubMed

    Enkirch, T; von Messling, V

    2015-05-01

    Emerging and well-known viral diseases remain one the most important global public health threats. A better understanding of their pathogenesis and mechanisms of transmission requires animal models that accurately reproduce these aspects of the disease. Here we review the role of ferrets as an animal model for the pathogenesis of different respiratory viruses with an emphasis on influenza and paramyxoviruses. We will describe the anatomic and physiologic characteristics that contribute to the natural susceptibility of ferrets to these viruses, and provide an overview of the approaches available to analyze their immune responses. Recent insights gained using this model will be highlighted, including the development of new prophylactic and therapeutic approaches. To provide decision criteria for the use of this animal model, its strengths and limitations will be discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Induced Pluripotent Stem Cells and Periodontal Regeneration.

    PubMed

    Du, Mi; Duan, Xuejing; Yang, Pishan

    Periodontitis is a chronic inflammatory disease which leads to destruction of both the soft and hard tissues of the periodontium. Tissue engineering is a therapeutic approach in regenerative medicine that aims to induce new functional tissue regeneration via the synergistic combination of cells, biomaterials, and/or growth factors. Advances in our understanding of the biology of stem cells, including embryonic stem cells and mesenchymal stem cells, have provided opportunities for periodontal tissue engineering. However, there remain a number of limitations affecting their therapeutic efficiency. Due to the considerable proliferation and differentiation capacities, recently described induced pluripotent stem cells (iPSCs) provide a new way for cell-based therapies for periodontal regeneration. This review outlines the latest status of periodontal tissue engineering and highlights the potential use of iPSCs in periodontal tissue regeneration.

  10. Management of acute pancreatitis in children.

    PubMed

    Abu-El-Haija, Maisam; Lin, Tom K; Nathan, Jaimie D

    2017-10-01

    Pediatric acute pancreatitis has been on the rise in the last decades, with an incidence close to adult pancreatitis. In the majority of cases acute pancreatitis resolves spontaneously, but in a subset of children the disease progresses to severe acute pancreatitis with attendant morbidity and mortality. Pediatric acute pancreatitis in this era is recognized as a separate entity from adult acute pancreatitis given that the causes and disease outcomes are different. There are slow but important advances made in understanding the best management for acute pancreatitis in children from medical, interventional, and surgical aspects. Supportive care with fluids, pain medications, and nutrition remain the mainstay for acute pancreatitis management. For complicated or severe pancreatitis, specialized interventions may be required with endoscopic or drainage procedures. Surgery has an important but limited role in pediatric acute pancreatitis.

  11. Reported chemical sensitivities in a health survey of United Kingdon military personnel

    PubMed Central

    Reid, S; Hotopf, M; Hull, L; Ismail, K; Unwin, C; Wessely, S

    2002-01-01

    Method: Cross sectional postal survey of three cohorts of United Kingdom military personnel comprising Gulf veterans (n=3531), those who had served in Bosnia (n=2050), and those serving during the Gulf war but not deployed there (Era cohort, n=2614). Results: Sensitivity to at least one everyday chemical was reported by a considerable proportion of all three cohorts, and particularly by veterans of the Gulf war (Era: 14%; Bosnia: 13%; Gulf: 28%). Conclusion: Reported chemical sensitivities were common in all three military cohorts. Our understanding of chemical sensitivities remains limited and objective evidence for a causal link between low level exposures to chemicals and reported symptoms is lacking. Given their frequency in the population, further work in this area is necessary. PMID:11886951

  12. Quantifying Drosophila food intake: comparative analysis of current methodology

    PubMed Central

    Deshpande, Sonali A.; Carvalho, Gil B.; Amador, Ariadna; Phillips, Angela M.; Hoxha, Sany; Lizotte, Keith J.; Ja, William W.

    2014-01-01

    Food intake is a fundamental parameter in animal studies. Despite the prevalent use of Drosophila in laboratory research, precise measurements of food intake remain challenging in this model organism. Here, we compare several common Drosophila feeding assays: the Capillary Feeder (CAFE), food-labeling with a radioactive tracer or a colorimetric dye, and observations of proboscis extension (PE). We show that the CAFE and radioisotope-labeling provide the most consistent results, have the highest sensitivity, and can resolve differences in feeding that dye-labeling and PE fail to distinguish. We conclude that performing the radiolabeling and CAFE assays in parallel is currently the best approach for quantifying Drosophila food intake. Understanding the strengths and limitations of food intake methodology will greatly advance Drosophila studies of nutrition, behavior, and disease. PMID:24681694

  13. Effects of hydrogen on thermal creep behaviour of Zircaloy fuel cladding

    NASA Astrophysics Data System (ADS)

    Suman, Siddharth; Khan, Mohd Kaleem; Pathak, Manabendra; Singh, R. N.

    2018-01-01

    Zirconium alloys are extensively used for nuclear fuel cladding. Creep is one of the most likely degradation mechanisms for fuel cladding during reactor operating and repository conditions. Fuel cladding tubes undergo waterside corrosion during service and hydrogen is produced as a result of it-a fraction of which is picked up by cladding. Hydrogen remains in solid solution up to terminal solid solubility and it precipitates as brittle hydride phase in the zirconium metal matrix beyond this limiting concentration. Hydrogen, either in solid solution or as precipitated hydride, alters the creep behaviour of zirconium alloys. The present article critically reviews the influence of hydrogen on thermal creep behaviour of zirconium alloys, develops the systematic understanding of this multifaceted phenomenon, and delineates the thrust areas which require further investigations.

  14. Computer-aided drug discovery.

    PubMed

    Bajorath, Jürgen

    2015-01-01

    Computational approaches are an integral part of interdisciplinary drug discovery research. Understanding the science behind computational tools, their opportunities, and limitations is essential to make a true impact on drug discovery at different levels. If applied in a scientifically meaningful way, computational methods improve the ability to identify and evaluate potential drug molecules, but there remain weaknesses in the methods that preclude naïve applications. Herein, current trends in computer-aided drug discovery are reviewed, and selected computational areas are discussed. Approaches are highlighted that aid in the identification and optimization of new drug candidates. Emphasis is put on the presentation and discussion of computational concepts and methods, rather than case studies or application examples. As such, this contribution aims to provide an overview of the current methodological spectrum of computational drug discovery for a broad audience.

  15. Multitrophic microbial interactions for eco- and agro-biotechnological processes: theory and practice.

    PubMed

    Saleem, Muhammad; Moe, Luke A

    2014-10-01

    Multitrophic level microbial loop interactions mediated by protist predators, bacteria, and viruses drive eco- and agro-biotechnological processes such as bioremediation, wastewater treatment, plant growth promotion, and ecosystem functioning. To what extent these microbial interactions are context-dependent in performing biotechnological and ecosystem processes remains largely unstudied. Theory-driven research may advance the understanding of eco-evolutionary processes underlying the patterns and functioning of microbial interactions for successful development of microbe-based biotechnologies for real world applications. This could also be a great avenue to test the validity or limitations of ecology theory for managing diverse microbial resources in an era of altering microbial niches, multitrophic interactions, and microbial diversity loss caused by climate and land use changes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Investigation of the Temperature Hysteresis Phenomenon of a Loop Heat Pipe

    NASA Technical Reports Server (NTRS)

    Kaya, Tarik; Ku, Jentung; Hoang, Triem; Cheung, Mark K.

    1999-01-01

    The temperature hysteresis phenomenon of a Loop Heat Pipe (LHP) was experimentally investigated. The temperature hysteresis was identified by the fact that the operating temperature depends upon not only the imposed power but also the previous history of the power variation. The temperature hysteresis could impose limitations on the LHP applications since the LHP may exhibit different steady-state operating temperatures at a given power input even when the condenser sink temperature remains unchanged. In order to obtain insight to this phenomenon, a LHP was tested at different elevations and tilts by using an elaborated power profile. A hypothesis was suggested to explain the temperature hysteresis. This hypothesis explains well the experimental observations. Results of this study provide a better understanding of the performance characteristics of the LHPS.

  17. Scratching the itch: new tools to advance understanding of scabies.

    PubMed

    Mounsey, Kate E; McCarthy, James S; Walton, Shelley F

    2013-01-01

    Scabies remains a significant public health problem worldwide. Research into aspects of Sarcoptes scabiei biology and host-parasite interactions has been impeded by an inability to maintain mites in vitro and by limited access to parasite material and infected subjects. The generation of comprehensive expressed sequence tag libraries has enabled the initial characterisation of molecules of interest to diagnostics, vaccines, and drug resistance. The recent development and utilisation of animal models, combined with next-generation technologies, is anticipated to lead to new strategies to prevent, diagnose, and treat scabies, ultimately improving skin health in both human and veterinary settings. This article will summarise recent molecular and immunologic advances on scabies, and will address priorities for the exciting 'next chapter' of scabies research. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Meeting Report: The Role of the Mobilome in Cancer.

    PubMed

    Ardeljan, Daniel; Taylor, Martin S; Burns, Kathleen H; Boeke, Jef D; Espey, Michael Graham; Woodhouse, Elisa C; Howcroft, Thomas Kevin

    2016-08-01

    Approximately half of the human genome consists of repetitive sequence attributed to the activities of mobile DNAs, including DNA transposons, RNA transposons, and endogenous retroviruses. Of these, only long interspersed elements (LINE-1 or L1) and sequences copied by LINE-1 remain mobile in our species today. Although cells restrict L1 activity by both transcriptional and posttranscriptional mechanisms, L1 derepression occurs in developmental and pathologic contexts, including many types of cancers. However, we have limited knowledge of the extent and consequences of L1 expression in premalignancies and cancer. Participants in this NIH strategic workshop considered key questions to enhance our understanding of mechanisms and roles the mobilome may play in cancer biology. Cancer Res; 76(15); 4316-9. ©2016 AACR. ©2016 American Association for Cancer Research.

  19. Limiting global-mean temperature increase to 1.5-2 °C could reduce the incidence and spatial spread of dengue fever in Latin America.

    PubMed

    Colón-González, Felipe J; Harris, Ian; Osborn, Timothy J; Steiner São Bernardo, Christine; Peres, Carlos A; Hunter, Paul R; Lake, Iain R

    2018-06-12

    The Paris Climate Agreement aims to hold global-mean temperature well below 2 °C and to pursue efforts to limit it to 1.5 °C above preindustrial levels. While it is recognized that there are benefits for human health in limiting global warming to 1.5 °C, the magnitude with which those societal benefits will be accrued remains unquantified. Crucial to public health preparedness and response is the understanding and quantification of such impacts at different levels of warming. Using dengue in Latin America as a study case, a climate-driven dengue generalized additive mixed model was developed to predict global warming impacts using five different global circulation models, all scaled to represent multiple global-mean temperature assumptions. We show that policies to limit global warming to 2 °C could reduce dengue cases by about 2.8 (0.8-7.4) million cases per year by the end of the century compared with a no-policy scenario that warms by 3.7 °C. Limiting warming further to 1.5 °C produces an additional drop in cases of about 0.5 (0.2-1.1) million per year. Furthermore, we found that by limiting global warming we can limit the expansion of the disease toward areas where incidence is currently low. We anticipate our study to be a starting point for more comprehensive studies incorporating socioeconomic scenarios and how they may further impact dengue incidence. Our results demonstrate that although future climate change may amplify dengue transmission in the region, impacts may be avoided by constraining the level of warming. Copyright © 2018 the Author(s). Published by PNAS.

  20. Limiting global-mean temperature increase to 1.5–2 °C could reduce the incidence and spatial spread of dengue fever in Latin America

    PubMed Central

    Harris, Ian; Osborn, Timothy J.; Steiner São Bernardo, Christine; Peres, Carlos A.; Lake, Iain R.

    2018-01-01

    The Paris Climate Agreement aims to hold global-mean temperature well below 2 °C and to pursue efforts to limit it to 1.5 °C above preindustrial levels. While it is recognized that there are benefits for human health in limiting global warming to 1.5 °C, the magnitude with which those societal benefits will be accrued remains unquantified. Crucial to public health preparedness and response is the understanding and quantification of such impacts at different levels of warming. Using dengue in Latin America as a study case, a climate-driven dengue generalized additive mixed model was developed to predict global warming impacts using five different global circulation models, all scaled to represent multiple global-mean temperature assumptions. We show that policies to limit global warming to 2 °C could reduce dengue cases by about 2.8 (0.8–7.4) million cases per year by the end of the century compared with a no-policy scenario that warms by 3.7 °C. Limiting warming further to 1.5 °C produces an additional drop in cases of about 0.5 (0.2–1.1) million per year. Furthermore, we found that by limiting global warming we can limit the expansion of the disease toward areas where incidence is currently low. We anticipate our study to be a starting point for more comprehensive studies incorporating socioeconomic scenarios and how they may further impact dengue incidence. Our results demonstrate that although future climate change may amplify dengue transmission in the region, impacts may be avoided by constraining the level of warming. PMID:29844166

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