Stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiation therapy (SABR), are rapidly becoming accepted practice for the radiation ...therapy of certain tumors. Typically, SRS and SBRT involve the delivery of 1 or a few large-dose fractions of 8 to 30 Gy per fraction: a major paradigm shift from radiation therapy practice over the past 90 years, when, with relatively large amounts of normal tissues receiving high doses, the goal was to maximize tumor response for an acceptable level of normal tissue injury. The development of SRS and SBRT have come about because of technologic advances in image guidance and treatment delivery techniques that enable the delivery of large doses to tumors with reduced margins and high gradients outside the target, thereby minimizing doses to surrounding normal tissues. Because the results obtained with SRS and SBRT have been impressive, they have raised the question whether classic radiobiological modeling, and the linear-quadratic (LQ) model, are appropriate for large doses per fraction. In addition to objections to the LQ model, the possibility of additional biological effects resulting from endothelial cell damage, enhanced tumor immunity, or both have been raised to account for the success of SRS and SBRT. In this review, we conclude that the available preclinical and clinical data do not support a need to change the LQ model or to invoke phenomena over and above the classic 5 Rs of radiobiology and radiation therapy, with the likely exception that for some tumors high doses of irradiation may produce enhanced antitumor immunity. Thus, we suggest that for most tumors, the standard radiobiology concepts of the 5 Rs are sufficient to explain the clinical data, and the excellent results obtained from clinical studies are the result of the much larger biologically effective doses that are delivered with SRS and SBRT.
Continued declines in coral reef health over the past three decades have been punctuated by severe mass coral bleaching‐induced mortality events that have grown in intensity and frequency under ...climate change. Intensive global research efforts have therefore persistently focused on bleaching phenomena to understand where corals bleach, when and why—resulting in a large—yet still somewhat patchy—knowledge base. Particularly catastrophic bleaching‐induced coral mortality events in the past 5 years have catalyzed calls for a more diverse set of reef management tools, extending far beyond climate mitigation and reef protection, to also include more aggressive interventions. However, the effectiveness of these various tools now rests on rapidly assimilating our knowledge base of coral bleaching into more integrated frameworks. Here, we consider how the past three decades of intensive coral bleaching research has established the basis for complex biological and environmental networks, which together regulate outcomes of bleaching severity. We discuss how we now have enough scaffold for conceptual biological and environmental frameworks underpinning bleaching susceptibility, but that new tools are urgently required to translate this to an operational system informing—and testing—bleaching outcomes. Specifically, adopting network models that can fully describe and predict metabolic functioning of coral holobionts, and how this functioning is regulated by complex doses and interactions among environmental factors. Identifying knowledge gaps limiting operation of such models is the logical step to immediately guide and prioritize future experiments and observations. We are at a time‐critical point where we can implement new capacity to resolve how coral bleaching patterns emerge from complex biological–environmental networks, and so more effectively inform rapidly evolving ecological management and social adaptation frameworks aimed at securing the future of coral reefs.
Intensive global research efforts over the past three decades have focused on the coral bleaching phenomena to understand when and why it occurs, resulting in a large—yet still somewhat patchy—knowledge base. We consider how these efforts have established the basis for complex biological and environmental networks as conceptual frameworks. However, new tools are required to translate these frameworks into operational systems that can more effectively predict bleaching outcomes that are urgently needed to inform rapidly evolving ecological management and support social adaptation.
Long recognized as a malodorous and highly toxic gas, recent experimental studies have revealed that hydrogen sulfide (H2S) is produced enzymatically in all mammalian species including man and exerts ...several critical actions to promote cardiovascular homeostasis and health. During the past 15 years, scientists have determined that H2S is produced by 3 endogenous enzymes and exerts powerful effects on endothelial cells, smooth muscle cells, inflammatory cells, mitochondria, endoplasmic reticulum, and nuclear transcription factors. These effects have been reported in multiple organ systems, and the majority of data clearly indicate that H2S produced by the endogenous enzymes exerts cytoprotective actions. Recent preclinical studies investigating cardiovascular diseases have demonstrated that the administration of physiological or pharmacological levels of H2S attenuates myocardial injury, protects blood vessels, limits inflammation, and regulates blood pressure. H2S has emerged as a critical cardiovascular signaling molecule similar to nitric oxide and carbon monoxide with a profound effect on the heart and circulation. Our improved understanding of how H2S elicits protective actions, coupled with the rapid development of novel H2S-releasing agents, has resulted in heightened enthusiasm for the clinical translation of this ephemeral gaseous molecule. This review will examine our current state of knowledge about the actions of H2S within the cardiovascular system with an emphasis on the therapeutic potential and molecular cross talk between H2S, nitric oxide, and carbon monoxide.
This book provides engineers with the safety and risk assessment tools and techniques they need to work effectively in any safety or reliability critical environment. These tools are primarily ...statistical. Where this book succeeds is by meeting the needs of an applied audience by setting these tools in the context of the design and operation of safety related processes and systems. Now in its Eighth Edition, this is regarded as the core reference in this field, and the success of its approach is reflected in the popularity of this standard work. This book deals with all aspects of reliability, safety-related systems, and the assessment and management of risk in a simple and straightforward way, pre-supposing no prior knowledge and dealing simply and realistically with numerical data by using the minimum of mathematical and technical jargon.
The value-capture problem for innovators in the digital economy involves some different challenges from those in the industrial economy. It inevitably requires understanding the dynamics of platforms ...and ecosystems. These challenges are amplified for enabling technologies, which are the central focus of this article. The innovator of an enabling technology has a special business model challenge because the applicability to many downstream verticals forecloses, as a practical matter, ownership of all the relevant complements. Complementary assets (vertical and lateral) in the digital context are no longer just potential value-capture mechanisms (through asset price appreciation or through preventing exposure to monopolistic bottleneck pricing by others); they may well be needed simply for the technology to function. Technological and innovational complementors present both coordination and market design challenges to the innovator that generally lead to market failure in the form of an excess of social over private returns. The low private return leads to socially sub-optimal underinvestment in future R&D that can be addressed to some extent by better strategic decision-making by the innovator and/or by far-sighted policies from government and the judiciary.
The default value-capture mechanism for many enabling technologies is the licensing of trade secrets and/or patents. Licensing is shown to be a difficult business model to implement from a value-capture perspective. When injunctions for intellectual property infringement are hard to win, or even to be considered, the incentives for free riding by potential licensees are considerable. Licensing is further complicated if it involves standard essential patents, as both courts and policy makers may fail to understand that development of a standard involves components of both interoperability and technology development. If a technology standard is not treated as the embodiment of significant R&D efforts enabling substantial new downstream economic activity, then rewards are likely to be calibrated too low to support appropriate levels of future innovation.
The labor market increasingly rewards social skills. Between 1980 and 2012, jobs requiring high levels of social interaction grew by nearly 12 percentage points as a share of the U.S. labor force. ...Math-intensive but less social jobs—including many STEM occupations—shrank by 3.3 percentage points over the same period. Employment and wage growth were particularly strong for jobs requiring high levels of both math skill and social skills. To understand these patterns, I develop a model of team production where workers “trade tasks” to exploit their comparative advantage. In the model, social skills reduce coordination costs, allowing workers to specialize and work together more efficiently. The model generates predictions about sorting and the relative returns to skill across occupations, which I investigate using data from the NLSY79 and the NLSY97. Using a comparable set of skill measures and covariates across survey waves, I find that the labor market return to social skills was much greater in the 2000s than in the mid-1980s and 1990s.
Socioeconomic position (SEP) is a multi-dimensional construct reflecting (and influencing) multiple socio-cultural, physical, and environmental factors. In a sample of 286,301 participants from UK ...Biobank, we identify 30 (29 previously unreported) independent-loci associated with income. Using a method to meta-analyze data from genetically-correlated traits, we identify an additional 120 income-associated loci. These loci show clear evidence of functionality, with transcriptional differences identified across multiple cortical tissues, and links to GABAergic and serotonergic neurotransmission. By combining our genome wide association study on income with data from eQTL studies and chromatin interactions, 24 genes are prioritized for follow up, 18 of which were previously associated with intelligence. We identify intelligence as one of the likely causal, partly-heritable phenotypes that might bridge the gap between molecular genetic inheritance and phenotypic consequence in terms of income differences. These results indicate that, in modern era Great Britain, genetic effects contribute towards some of the observed socioeconomic inequalities.
Mindfulness Interventions Creswell, J. David
Annual review of psychology,
01/2017, Volume:
68, Issue:
1
Journal Article
Peer reviewed
Open access
Mindfulness interventions aim to foster greater attention to and awareness of present moment experience. There has been a dramatic increase in randomized controlled trials (RCTs) of mindfulness ...interventions over the past two decades. This article evaluates the growing evidence of mindfulness intervention RCTs by reviewing and discussing (
a
) the effects of mindfulness interventions on health, cognitive, affective, and interpersonal outcomes; (
b
) evidence-based applications of mindfulness interventions to new settings and populations (e.g., the workplace, military, schools); (
c
) psychological and neurobiological mechanisms of mindfulness interventions; (
d
) mindfulness intervention dosing considerations; and (
e
) potential risks of mindfulness interventions. Methodologically rigorous RCTs have demonstrated that mindfulness interventions improve outcomes in multiple domains (e.g., chronic pain, depression relapse, addiction). Discussion focuses on opportunities and challenges for mindfulness intervention research and on community applications.
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