Communicating scientific uncertainty Fischhoff, Baruch; Davis, Alex L.
Proceedings of the National Academy of Sciences - PNAS,
09/2014, Volume:
111, Issue:
Supplement 4
Journal Article
Peer reviewed
Open access
All science has uncertainty. Unless that uncertainty is communicated effectively, decision makers may put too much or too little faith in it. The information that needs to be communicated depends on ...the decisions that people face. Are they (i) looking for a signal (e.g., whether to evacuate before a hurricane), (ii) choosing among fixed options (e.g., which medical treatment is best), or (iii) learning to create options (e.g., how to regulate nanotechnology)? We examine these three classes of decisions in terms of how to characterize, assess, and convey the uncertainties relevant to each. We then offer a protocol for summarizing the many possible sources of uncertainty in standard terms, designed to impose a minimal burden on scientists, while gradually educating those whose decisions depend on their work. Its goals are better decisions, better science, and better support for science.
Traces of Drosophila Memory Davis, Ronald L.
Neuron (Cambridge, Mass.),
04/2011, Volume:
70, Issue:
1
Journal Article
Peer reviewed
Open access
Studies using functional cellular imaging of living flies have identified six memory traces that form in the olfactory nervous system after conditioning with odors. These traces occur in distinct ...nodes of the olfactory nervous system, form and disappear across different windows of time, and are detected in the imaged neurons as increased calcium influx or synaptic release in response to the conditioned odor. Three traces form at or near acquisition and coexist with short-term behavioral memory. One trace forms with a delay after learning and coexists with intermediate-term behavioral memory. Two traces form many hours after acquisition and coexist with long-term behavioral memory. The transient memory traces may support behavior across the time windows of their existence. The experimental approaches for dissecting memory formation in the fly, ranging from the molecular to the systems, make it an ideal system for elucidating the logic by which the nervous system organizes and stores different temporal forms of memory.
Anthracyclines are the critical component in a majority of pediatric chemotherapy regimens due to their broad anticancer efficacy. Unfortunately, the vast majority of long-term childhood cancer ...survivors will develop a chronic health condition caused by their successful treatments and severe cardiac disease is a common life-threatening outcome that is unequivocally linked to previous anthracycline exposure. The intricacies of how anthracyclines such as doxorubicin, damage the heart and initiate a disease process that progresses over multiple decades is not fully understood. One area left largely unstudied is the role of the cardiac fibroblast, a key cell type in cardiac maturation and injury response. In this study, we demonstrate the effect of doxorubicin on cardiac fibroblast function in the presence and absence of the critical DNA damage response protein p53. In wildtype cardiac fibroblasts, doxorubicin-induced damage correlated with decreased proliferation and migration, cell cycle arrest, and a dilated cardiomyopathy gene expression profile. Interestingly, these doxorubicin-induced changes were completely or partially restored in p53-/- cardiac fibroblasts. Moreover, in wildtype cardiac fibroblasts, doxorubicin produced DNA damage and mitochondrial dysfunction, both of which are well-characterized cell stress responses induced by cytotoxic chemotherapy and varied forms of heart injury. A 3-fold increase in p53 (p = 0.004) prevented the completion of mitophagy (p = 0.032) through sequestration of Parkin. Interactions between p53 and Parkin increased in doxorubicin-treated cardiac fibroblasts (p = 0.0003). Finally, Parkin was unable to localize to the mitochondria in wildtype cardiac fibroblasts, but mitochondrial localization was restored in p53-/- cardiac fibroblasts. These findings strongly suggest that cardiac fibroblasts are an important myocardial cell type that merits further study in the context of doxorubicin treatment. A more robust knowledge of the role cardiac fibroblasts play in the development of doxorubicin-induced cardiotoxicity will lead to novel clinical strategies that will improve the quality of life of cancer survivors.
Food fights over free trade Davis, Christina L
2003, 2011., 20111023, 2011, 2003-01-01, 20030101
eBook, Book
This detailed account of the politics of opening agricultural markets explains how the institutional context of international negotiations alters the balance of interests at the domestic level to ...favor trade liberalization despite opposition from powerful farm groups. Historically, agriculture stands out as a sector in which countries stubbornly defend domestic programs, and agricultural issues have been the most frequent source of trade disputes in the postwar trading system. While much protection remains, agricultural trade negotiations have resulted in substantial concessions as well as negotiation collapses. Food Fights over Free Trade shows that the liberalization that has occurred has been due to the role of international institutions.
Psychological studies in humans and behavioral studies of model organisms suggest that forgetting is a common and biologically regulated process, but the molecular, cellular, and circuit mechanisms ...underlying forgetting are poorly understood. Here we show that the bidirectional modulation of a small subset of dopamine neurons (DANs) after olfactory learning regulates the rate of forgetting of both punishing (aversive) and rewarding (appetitive) memories. Two of these DANs, MP1 and MV1, exhibit synchronized ongoing activity in the mushroom body neuropil in alive and awake flies before and after learning, as revealed by functional cellular imaging. Furthermore, while the mushroom-body-expressed dDA1 dopamine receptor is essential for the acquisition of memory, we show that the dopamine receptor DAMB, also highly expressed in mushroom body neurons, is required for forgetting. We propose a dual role for dopamine: memory acquisition through dDA1 signaling and forgetting through DAMB signaling in the mushroom body neurons.
► Dopamine neuron synaptic function regulates forgetting of olfactory memories ► Dopamine neurons exhibit ongoing activity in the mushroom bodies in vivo ► The dopamine receptor DAMB mediates dopamine-based forgetting
Berry et al. utilize bidirectional modulation of neuronal activity, in vivo functional imaging, and receptor mutant analysis to show that dopamine has a dual role in both the acquisition of olfactory memories and the forgetting of these memories.
Abstract Pilot studies represent a fundamental phase of the research process. The purpose of conducting a pilot study is to examine the feasibility of an approach that is intended to be used in a ...larger scale study. The roles and limitations of pilot studies are described here using a clinical trial as an example. A pilot study can be used to evaluate the feasibility of recruitment, randomization, retention, assessment procedures, new methods, and implementation of the novel intervention. A pilot study is not a hypothesis testing study. Safety, efficacy and effectiveness are not evaluated in a pilot. Contrary to tradition, a pilot study does not provide a meaningful effect size estimate for planning subsequent studies due to the imprecision inherent in data from small samples. Feasibility results do not necessarily generalize beyond the inclusion and exclusion criteria of the pilot design. A pilot study is a requisite initial step in exploring a novel intervention or an innovative application of an intervention. Pilot results can inform feasibility and identify modifications needed in the design of a larger, ensuing hypothesis testing study. Investigators should be forthright in stating these objectives of a pilot study. Grant reviewers and other stakeholders should expect no more.
Tissue regeneration is an orchestrated progression of cells from an immature state to a mature one, conventionally represented as distinctive cell subsets. A continuum of transitional cell states ...exists between these discrete stages. We combine the depth of single-cell mass cytometry and an algorithm developed to leverage this continuum by aligning single cells of a given lineage onto a unified trajectory that accurately predicts the developmental path de novo. Applied to human B cell lymphopoiesis, the algorithm (termed Wanderlust) constructed trajectories spanning from hematopoietic stem cells through to naive B cells. This trajectory revealed nascent fractions of B cell progenitors and aligned them with developmentally cued regulatory signaling including IL-7/STAT5 and cellular events such as immunoglobulin rearrangement, highlighting checkpoints across which regulatory signals are rewired paralleling changes in cellular state. This study provides a comprehensive analysis of human B lymphopoiesis, laying a foundation to apply this approach to other tissues and “corrupted” developmental processes including cancer.
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•Wanderlust aligns single cells on a trajectory according to their developmental path•Mass cytometry plus Wanderlust infers path from HSCs to naive B cells•Trajectory identifies precursor B cell populations where rearrangement occurs•Discovery of coordination points dictating cell fate decisions
Combining single-cell mass cytometry data from a population of cells from human tissue with a new algorithm that leverages the single-cell data to order the cells along their developmental trajectory provides insight into B cell development and paves the for similar analyses in other tissues.
Purpose of Review
Parkinson’s disease (PD) is a complex neurodegenerative disorder, the aetiology of which is still largely unknown. Overwhelming evidence indicates that mitochondrial dysfunction is ...a central factor in PD pathophysiology. Here we review recent developments around mitochondrial dysfunction in familial and sporadic PD, with a brief overview of emerging therapies targeting mitochondrial dysfunction.
Recent Findings
Increasing evidence supports the critical role for mitochondrial dysfunction in the development of sporadic PD, while the involvement of familial PD-related genes in the regulation of mitochondrial biology has been expanded by the discovery of new mitochondria-associated disease loci and the identification of their novel functions.
Summary
Recent research has expanded knowledge on the mechanistic details underlying mitochondrial dysfunction in PD, with the discovery of new therapeutic targets providing invaluable insights into the essential role of mitochondria in PD pathogenesis and unique opportunities for drug development.
New approaches, techniques and tools invented over the last decade and a half have revolutionized the functional dissection of neural circuitry underlying "Drosophila" learning. The new methodologies ...have been used aggressively by researchers attempting to answer three critical questions about olfactory memories formed with appetitive and aversive reinforcers: (1) Which neurons within the olfactory nervous system mediate the acquisition of memory? (2) What is the complete neural circuitry extending from the site(s) of acquisition to the site(s) controlling memory expression? (3) How is information processed across this circuit to consolidate early-forming, disruptable memories to stable, late memories? Much progress has been made and a few strong conclusions have emerged: (1) Acquisition occurs at multiple sites within the olfactory nervous system but is mediated predominantly by the ? mushroom body neurons. (2) The expression of long-term memory is completely dependent on the synaptic output of a/ß mushroom body neurons. (3) Consolidation occurs, in part, through circuit interactions between mushroom body and dorsal paired medial neurons. Despite this progress, a complete and unified model that details the pathway from acquisition to memory expression remains elusive.
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