Development Of More Sophisticated Tools Research Articles

Risk management of skin sensitisers: A commentary

Historically, allergic contact dermatitis (ACD) to chemicals encouraged hazard identification improvements, more sophisticated risk assessment and implementation of regulatory strategies, including banning of specific sensitising substances. The validation process applied to hazard identification methods demonstrates their accuracy; their use to characterise sensitiser potency facilitates quantitative and transparent risk assessment. Diagnostic patch testing at dermatology clinics worldwide delivers feedback showing where risk assessment/management has been insufficient or did not target the exposure of concern, thereby facilitating improvements. When urgent action to protect human health was required, regulations limited/banned, specific skin sensitisers. This can be seen in practice with the fragrance industry, a known source of ACD, thus requiring risk management, usually restrictions to limit allergy induction, and very rarely specific bans on ingredients. Experience and development of more sophisticated tools, e.g. to assess aggregate exposure from multitude of consumer product types, has led to repeated adaptation of risk assessment and promulgation of updated fragrance use limits. Although targeted control may not always lead to rapid change in the overall clinical picture, it is preferable to a blanket undifferentiated regulatory control of all sensitisers, resulting in unwarranted restrictions for many uses of no health concern, with consequent substantial socio-economic impacts.

Cell of origin of glioma: biological and clinical implications

The cellular origin of gliomas remains a topic of controversy in cancer research. Advances in neurobiology, molecular genetics, and functional genomics have ushered new insights through exploiting the development of more sophisticated tools to address this question. Diverse distinct cell populations in the adult brain have been reported to give rise to gliomas, although how these studies relate physiologically to mechanisms of spontaneous tumour formation via accumulation of tumour-initiating mutations within a single cell are less well developed. Recent studies in animal models indicate that the lineage of the tumour-initiating cell may contribute to the biological and genomic phenotype of glioblastoma. These results suggest that the cell of origin may not only serve as a source of diversity for these tumours, but may also provide new avenues for improved diagnostics and therapeutic targeting that may prolong the lives of patients.

Sedentary Behavior Research Priorities--NHLBI/NIA Sedentary Behavior Workshop Summary.

INTRODUCTION AND WORKSHOP PURPOSE Over the course of 2013, the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute on Aging (NIA) collaborated with a multinational group of expert scientists to convene, host, and facilitate a four-part virtual webinar workshop on sedentary behavior. Participants met to evaluate and discuss the current epidemiological, clinical, and other relevant literature on sedentary behavior and to identify research priorities relative to preventing cardiovascular disease and mitigating aging-related disability and functional outcomes. The workshop was predicated on findings of insufficient levels of population adherence to current physical activity recommendations (1,12) and the need to address the NHLBI and NIA research portfolio gaps in the area of sedentary behavior. Scientific rationale No consistent definition of sedentary behavior currently exists. However, sitting, lying down, watching television, and participating in other screen-based activities are collectively labeled sedentary behaviors. In general, sedentary behavior consists of activities that do not increase energy expenditure markedly above resting metabolic levels (15). Consequently, they qualify as low energy-expenditure activities (15), which are associated with adverse metabolic and physical health outcomes with prolonged exposure (5,7–11,18). In contrast, high-energy expenditure activities confer health benefits with prolonged exposure, and this knowledge undergirds current physical activity recommendations (2,6,17,19). Although physical activity recommendations for moderate-to-vigorous intensity activities are based on strong evidence, they have yet to translate into sustained changes in population-level behaviors. In fact, the majority of the U.S. population is considered mostly inactive and sedentary (2,3,6). Yet, the health consequences of sedentary behavior are not clearly understood (4,5,7–11,18). Current knowledge suggests negative associations between sedentary behavior and health outcomes and indicates that the adverse effects associated with sedentary behavior are separate from those associated with low levels of moderate-to-vigorous intensity activities (13,14). Consequently, a knowledge gap remains regarding the independent effects of sedentary behavior on health outcomes, how sedentary behavior research fits into the vast knowledge base on physical activity, and how current and future knowledge about sedentary behavior can inform future health recommendations. Framing the workshop In an effort to engage all stakeholders, the NHLBI and NIA released a joint “Request for Information (RFI)” in January 2013 entitled “Request for Information (RFI) for High-Priority Research Topics for Sedentary Behavior—NOT-HL-13-166” (16). This RFI sought stakeholders’ perspectives on unanswered research questions in several areas, including approaches needed to evaluate and measure sedentary behavior in different populations, types of interventions and strategies needed to reduce the high prevalence of sedentary behaviors in the U.S., and identification of barriers and opportunities for translating current scientific knowledge into population health improvements. The substantial number of responses NHLBI and NIA received guided the workshop planning, identification of discussion topics, and formulation of the four thematic sessions: 1) Epidemiology of Sedentary Behavior; 2) Physiology of Sedentary Behavior and its Relationship to Health Outcomes; 3) Influences on Sedentary Behavior and Interventions to Reduce Sedentary Behavior; and 4) Novel Strategies for Sedentary Behavior Research. Premeeting activities and charge to the key participants Leading expert scientists in the four thematic areas were invited to participate as session coordinators, key presenters or audience participants. Teams of five to seven experts developed four or five concise 10-min presentations, which served as the framework for discussions in each of the four, 2.5-h virtual meetings. An additional group of invited scientists served as panel discussants for each session and provided summary comments and provocative questions that fostered deeper discussion of key issues. All of the discussions were facilitated by the meeting co-chairs, Dr. Russell Pate and Dr. Roger Fielding. WORKSHOP SUMMARY To capture the key findings of the workshop, the meeting chair concluded each session by identifying the two top priority recommendations. Comprehensive summaries of the meetings are presented in four brief white papers that accompany this document and include the substance of the presentations and discussions, a list of all the recommendations that emerged, and the final two priority recommendations for each session. Each of the white papers also reflects the specific themes discussed in one of the four sessions and includes substantial input from the session expert scientists and discussants convened for that particular session. As such, the authors of the white papers had the flexibility to present their recommendations in the manner that best captured their sessions’ theme, tone, and discussion. Across all sessions, participants varied in their use and definition of the concept of sedentary behavior. In fact, the terms “sedentary behavior,” “sedentary time,” and “sedentariness” were all used to inform the discussions. Consequently, in the interest of authenticity, the four white papers also reflect this variety of usage and perspectives. In the paragraphs below, summaries of the discussions for each of the workshop sessions are presented briefly. However, details with supporting rationale for all the recommendations can be found in the accompanying white papers. Webinar no. 1—The epidemiology of sedentary behavior The initial workshop session was dedicated to reviewing and discussing several issues basic to the study of sedentary behavior and its impact on health. Much attention was given to the definitions of sedentary behavior proposed previously and their implications for measurement of sedentary behavior in research studies. Workshop participants reviewed the current status of epidemiological research that has examined relationships between sedentary behavior and health outcomes and overviewed studies that have examined interactive influences of sedentary behavior and physical activity. They concluded that consensus regarding conceptual and operational definitions of sedentary behavior, better methods for measuring sedentary behavior in research studies, and large-scale prospective observational studies of the effects of sedentary behavior on multiple health outcomes are needed. Webinar no. 2—Physiology of sedentary behavior and its relationship to health outcomes The second webinar focused on the current state of understanding of the biological/physiological mechanisms that underlie sedentary behavior. Key areas of focus included cardiometabolic consequences of sedentary behavior, animal models of sedentary behavior or forced inactivity, and the interaction between central neurologic drivers of sedentary behavior and peripheral adaptation and feedback. Limitations in the current understanding of the molecular changes that occur with sedentary behavior were noted, in particular the fact that the molecular evidence for sedentary behavior effects is derived primarily from studies of conditions and models of low physical activity. Participants resolved that while low physical activity and sedentary behavior are likely to be related mechanistically, they are distinct entities. Discussion also focused on the need to develop better methodologies to address sedentary behavior, including further investigation of appropriate animal models and systems. Webinar participants identified several key research needs going forward, including understanding the interaction between central and peripheral mediators of sedentary behavior and the resultant biological consequences, understanding the molecular basis for the role of changes in sedentary behavior in accelerating the loss of aerobic capacity, and examining muscle performance with advancing age. Webinar no. 3—Influences on sedentary behavior and interventions to reduce sedentary behavior The third webinar focused on intervention strategies designed to reduce sedentary behavior. The main conclusion from this webinar was that interventions targeting sedentary behavior are conceptually and operationally distinct from interventions targeting physical activity. In reviewing the evidence on at-risk populations (e.g., children, older adults) and levels of intervention (e.g., community, workplace, individual), participants concluded that the needs of populations vary and recommended that future endeavors carefully consider the levels (community, work place, individual) for which interventions are to be developed and the populations to which they are targeted. The complexity of messaging to the public and the biomedical community surrounding the topic of sedentary behavior and a clear need for consensus around this message also were considered. Finally, participants proposed novel approaches to address questions related to the dose–response effects of changing sedentary behavior, the establishment of clinically meaningful changes in sedentary behavior, and development of more sophisticated tools to quantify sedentary behavior exposure. Webinar no. 4—Novel strategies for sedentary behavior research The final workshop session focused on unique and efficient strategies for conducting research on sedentary behavior and health. The workshop examined the need for research on sedentary behavior across a wide range of issues and noted that most of the current evidence linking sedentary behavior to health is based on observational studies. Ultimately, evidence will be needed to establish public health guidelines and public health interventions aimed at reducing sedentary behavior. Much discussion focused on the availability of databases that could support important research on sedentary behavior. These include data sets generated in ongoing large-scale epidemiologic studies in which accelerometry data have been or are being collected. These data, although typically collected for the purpose of measuring physical activity, can be reduced to measure sedentary behavior as well, and thus are a potentially valuable resource for future research in this area. Likewise, patient data included in the electronic health records of large integrated health systems provide opportunities for comparative effectiveness research and observational studies of sedentary behavior in patient populations. CONCLUSIONS This workshop was convened to engage expert extramural scientists in a series of discussions to identify critical gaps in the literature on sedentary behavior and cardiovascular and aging health outcomes. Themes that cut across the four meeting sessions included the need to develop a consensus definition, to validate and standardize assessment methods (both objective and subjective) to provide for accuracy and consistency, and to develop appropriate scientific models of research. Other topics included the use of translational models to understand personal, social, and environmental determinants of sedentary behavior; development of pragmatic trials using large networks of integrated health systems to aid with measurement, prevalence, and incidence data collection; exploration of the link between incidence rate and risk factors; and the use of technology. Significant discussions focused on whether sedentary behavior should be considered as a distinct and separate behavior from physical inactivity with separate adverse effects on health. To this end, the workshop summary proposed that future studies should seek to examine the separate and interactive effects of sedentary behavior and moderate-to-vigorous physical activity. In addition, it highlighted the importance of looking at patterns of sedentary behavior, developing and testing multilevel interventions, and exploring dose–response relationships of sedentary behavior to health outcomes. Participants acknowledged that sedentary behavior presents a unique challenge for which the strategies used to increase physical activity may not be suited. That notwithstanding, the research community should make concerted efforts to study and understand sedentary behaviors and to intervene to effect positive health outcomes and ensure that appropriate resources be directed to this endeavor. The workshop was sponsored by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the Office of Disease Prevention of the National Institutes of Health. The views expressed in this document reflect the collective ideas and opinions of the authors and do not necessarily represent the official views of the National Institutes of Health, the U.S. Department of Health and Human Services, or the other workshop participants. Dr. Fielding’s participation in this project was partially supported by the U.S. Department of Agriculture, under agreement no. 58-19500-014, and the Boston Claude D. Pepper Older Americans Independence Center (1P30AG031679). Any opinions, findings, conclusion, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of the U.S. Department of Agriculture. Dr. Fielding receives grant support from the U.S. Department of Agriculture, National Institutes of Health, Nestec Ltd., and Regeneron Pharmaceutical; is a consultant to Regeneron Pharmaceuticals and Nestec, Ltd; serves on the Scientific Advisory Boards of Cytokinetics, Inc., Pronutria, Inc., Amonnett, Inc., and Inside Tracker, Inc,; and owns stock or options in Pronutria, Amonnett, Inc., Inside Tracker, and Myosyntax. Dr. Pate receives grant support from the National Institutes of Health, Centers for Disease Control and Prevention, Duke Endowment, and FTZ Coca-Cola Service Company. He serves on the Scientific Advisory Board of Curves, Inc. The other authors have no potential conflicts.

Incorporating Risk and Uncertainty in a Multi-Criteria Process

The increasing intensity of competition, the development of more sophisticated tools for decision-making, and advances in information technology (IT) have led organisations to search for more efficient and effective ways to make key decisions. To succeed in rapidly changing competitive business environments firms can no longer ignore decision complexity, which arises from large numbers of alternative possibilities, and conflicting criteria. Traditional theory-based assessment techniques overemphasise quantitative and economic analysis, whereas senior managers often tend to base their final choice on qualitative and non-economic “strategic” factors. In this paper, senior managers of a European communications company made a key corporate decision that involved considerable risk and uncertainty by using Real Options (RO) theory embedded within a Direct-Interactive Structured-Criteria (DISC) Multi-Criteria Decision-Making (MCDM) system. We describe a case that shows how RO scores for the alternatives can, in a holistic manner, feed into the appropriate part the criteria structure effectively, thus combining both the quantitative and qualitative aspects of the decision. The DISC MCDM approach used several decision phases to narrow down the number of alternatives from six to three, and then two. At this point a “Magnifying Glass” approach was used, focusing on and enhancing the financial part of the criteria tree that differentiated the two remaining alternatives, when finally making the decision. These and other aspects of the decision process were selected to be compatible with the decision-makers’ own thinking processes, and were informed by nomology, the “Science of the laws of the Mind”.

Medical Use of Nanoparticles

Researchers today are able to encapsulate medicine in nanoparticles, the size of viruses. The nanoparticles are effective for drug delivery—the delivery of the medicine to the body—because they can very precisely find diseased cells and carry the medicine to them. This means that one can suffice with less dosage and thereby fewer side effects. In addition, nanoscience and nanotechnological methods are spurring the development of more sophisticated tools for detecting diseases, such as cancer and atherosclerosis, at early stages and performing neurosurgery. Applications of nanotechnology in disease diagnoses are developing rapidly. Their unique size-dependent properties make these materials superior and indispensable in many areas of human activity.

Response to Letters Regarding Article, “Relationship Between Nonsustained Ventricular Tachycardia After Non-ST-Elevation Acute Coronary Syndrome and Sudden Cardiac Death: Observations From the Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) Randomized Controlled Trial”

We thank Dr Madias for his insightful comments regarding the limitations of current clinical risk stratification for sudden cardiac death after an acute coronary syndrome and the great clinical need for the development of more sophisticated tools. With over 40 000 days of continuous electrocardiogram monitoring, the Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 36 Trial (MERLIN-TIMI 36) is a rich database for future research, and we are currently investigating whether specific morphological features may identify a subset of more lethal ventricular arrhythmias. We appreciate Dr Madias's suggestions for additional analyses and have embarked on an evaluation of novel electrocardiogram techniques, such as heart …

DNA-based methods for monitoring invasive species: a review and prospectus

The recent explosion of interest in DNA-based tools for species identification has prompted widespread speculation on the future availability of inexpensive, rapid, and accurate means of identifying specimens and assessing biodiversity. One applied field that may benefit dramatically from the development of such technologies is the detection, identification, and monitoring of invasive species. Recent studies have demonstrated the feasibility of DNA-based tools for such important tasks as confirmation of specimen identity and targeted screening for known or anticipated invaders. However, significant technological hurdles must be overcome before more ambitious applications, including estimation of propagule pressure and comprehensive surveys of complex environmental samples, are to be realized. Here we review existing methods, examine the technical difficulties associated with development of more sophisticated tools, and consider the potential utility of these DNA-based technologies for various applications relevant to invasive species monitoring.