Talk at the brink Gibson, David R
2012., 20120729, 2012, 2012-07-29, 20120101
eBook
In October 1962, the fate of the world hung on the American response to the discovery of Soviet nuclear missile sites in Cuba. That response was informed by hours of discussions between John F. ...Kennedy and his top advisers. What those advisers did not know was that President Kennedy was secretly taping their talks, providing future scholars with a rare inside look at high-level political deliberation in a moment of crisis.Talk at the Brinkis the first book to examine these historic audio recordings from a sociological perspective. It reveals how conversational practices and dynamics shaped Kennedy's perception of the options available to him, thereby influencing his decisions and ultimately the outcome of the crisis.
David Gibson looks not just at the positions taken by Kennedy and his advisers but how those positions were articulated, challenged, revised, and sometimes ignored. He argues that Kennedy's decisions arose from the intersection of distant events unfolding in Cuba, Moscow, and the high seas with the immediate conversational minutia of turn-taking, storytelling, argument, and justification. In particular, Gibson shows how Kennedy's group told and retold particular stories again and again, sometimes settling upon a course of action only after the most frightening consequences were omitted or actively suppressed.
Talk at the Brinkpresents an image of Kennedy's response to the Cuban missile crisis that is sharply at odds with previous scholarship, and has important implications for our understanding of decision making, deliberation, social interaction, and historical contingency.
Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to ...be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called "inflamm-aging." Despite research there is no clear understanding about the causes of "inflamm-aging" that underpin most major age-related diseases, including atherosclerosis, diabetes, Alzheimer's disease, rheumatoid arthritis, cancer, and aging itself. While inflammation is part of the normal repair response for healing, and essential in keeping us safe from bacterial and viral infections and noxious environmental agents, not all inflammation is good. When inflammation becomes prolonged and persists, it can become damaging and destructive. Several common molecular pathways have been identified that are associated with both aging and low-grade inflammation. The age-related change in redox balance, the increase in age-related senescent cells, the senescence-associated secretory phenotype (SASP) and the decline in effective autophagy that can trigger the inflammasome, suggest that it may be possible to delay age-related diseases and aging itself by suppressing pro-inflammatory molecular mechanisms or improving the timely resolution of inflammation. Conversely there may be learning from molecular or genetic pathways from long-lived cohorts who exemplify good quality aging. Here, we will discuss some of the current ideas and highlight molecular pathways that appear to contribute to the immune imbalance and the cytokine dysregulation, which is associated with "inflammageing" or parainflammation. Evidence of these findings will be drawn from research in cardiovascular disease, cancer, neurological inflammation and rheumatoid arthritis.
The US Supreme Court conducts much of its business through talk, including during oral arguments, where a central activity is the consideration of hypotheticals posed by justices. Using conversation ...analysis, I examine a key segment of the oral arguments for
Citizens United v. FEC
, one that arguably changed the course of campaign finance history. I identify the conversational devices employed to advance and contest one particular hypothetical, involving an imagined ban on books, subject to a speech-exchange system that differentially empowers justices to dictate both the terms of the discussion and the time afforded the advocate to respond to any particular question. The article offers the first disciplined qualitative analysis of interaction during oral arguments, illustrates the place of temporality in legal reasoning and argumentation, and makes several contributions to conversation analysis: it advances the study of institutional talk to a new legal setting, identifies some ways in which the machinery of talk can be harnessed for rhetorical effect, and demonstrates the analytical utility of prior knowledge of what a participant arrives to an encounter equipped to say.
Rheumatoid arthritis (RA) is a chronic autoimmune condition, characterised by joint pain, damage and disability, which can be addressed in a high proportion of patients by timely use of targeted ...biologic treatments. However, the patients, non-responsive to the treatments often suffer from refractoriness of the disease, leading to poor quality of life. Additionally, the biologic treatments are expensive. We obtained plasma samples from N = 144 participants with RA, who were about to commence anti-tumour necrosis factor (anti-TNF) therapy. These samples were sent to Olink Proteomics, Uppsala, Sweden, where proximity extension assays of 4 panels, containing 92 proteins each, were performed. A total of n = 89 samples of patients passed the quality control of anti-TNF treatment response data. The preliminary analysis of plasma protein expression values suggested that the RA population could be divided into two distinct molecular sub-groups (endotypes). However, these broad groups did not predict response to anti-TNF treatment, but were significantly different in terms of gender and their disease activity. We then labelled these patients as responders (n = 60) and non-responders (n = 29) based on the change in disease activity score (DAS) after 6 months of anti-TNF treatment and applied machine learning (ML) with a rigorous 5-fold nested cross-validation scheme to filter 17 proteins that were significantly associated with the treatment response. We have developed a ML based classifier ATRPred (anti-TNF treatment response predictor), which can predict anti-TNF treatment response in RA patients with 81% accuracy, 75% sensitivity and 86% specificity. ATRPred may aid clinicians to direct anti-TNF therapy to patients most likely to receive benefit, thus save cost as well as prevent non-responsive patients from refractory consequences. ATRPred is implemented in R.
Massive open online courses (MOOCs) have been the subject of much polarised debate around their potential to transform higher education in terms of opening access. Although MOOCs have been attracting ...large learner cohorts, concerns have emerged from the early evidence base centring upon issues of quality in learning and teaching provision, and there is clear evidence that impressive headline figures on MOOC enrolments often contrast with extremely low course completion rates. To address these concerns of quality, low retention and the need for engagement, this paper provides a review and case study of MOOC provision. The review considers the current position of MOOCs as a change agent for higher education provision, and the case study considers lessons learnt from an Astronomy MOOC which uses the Open2Study platform. This paper asks about new engagement strategies needed for face-to-face and online learners, and explores how course retention can be improved in online provision. Author abstract
Host specificity has a major influence on a parasite's ability to shift between human and animal host species. Yet there is a dearth of quantitative approaches to explore variation in host ...specificity across biogeographical scales, particularly in response to the varying community compositions of potential hosts. We built a global dataset of intermediate host associations for nine of the world's most widespread helminth parasites (all of which infect humans). Using hierarchical models, we asked if realised parasite host specificity varied in response to regional variation in the phylogenetic and functional diversities of potential host species. Parasites were recorded in 4–10 zoogeographical regions, with some showing considerable geographical variation in observed versus expected host specificity. Parasites generally exhibited the lowest phylogenetic host specificity in regions with the greatest variation in prospective host phylogenetic diversity, namely the Neotropical, Saharo‐Arabian and Australian regions. Globally, we uncovered notable variation in parasite host shifting potential. Observed host assemblages for Hydatigera taeniaeformis and Hymenolepis diminuta were less phylogenetically diverse than expected, suggesting limited potential to spillover into unrelated hosts. Host assemblages for Echinococcus granulosus, Mesocestoides lineatus and Trichinella spiralis were less functionally diverse than expected, suggesting limited potential to shift across host ecological niches. By contrast, Hyd. taeniaeformis infected a higher functional diversity of hosts than expected, indicating strong potential to shift across hosts with different ecological niches. We show that the realised phylogenetic and functional diversities of infected hosts are determined by biogeographical gradients in prospective host species pools. These findings emphasise the need to account for underlying species diversity when assessing parasite host specificity. Our framework to identify variation in realised host specificity is broadly applicable to other host–parasite systems and will provide key insights into parasite invasion potential at regional and global scales.
Optimal background matching camouflage Michalis, Constantine; Scott-Samuel, Nicholas E.; Gibson, David P. ...
Proceedings - Royal Society. Biological sciences/Proceedings - Royal Society. Biological Sciences,
07/2017, Letnik:
284, Številka:
1858
Journal Article
Recenzirano
Odprti dostop
Background matching is the most familiar and widespread camouflage strategy: avoiding detection by having a similar colour and pattern to the background. Optimizing background matching is ...straightforward in a homogeneous environment, or when the habitat has very distinct sub-types and there is divergent selection leading to polymorphism. However, most backgrounds have continuous variation in colour and texture, so what is the best solution? Not all samples of the background are likely to be equally inconspicuous, and laboratory experiments on birds and humans support this view. Theory suggests that the most probable background sample (in the statistical sense), at the size of the prey, would, on average, be the most cryptic. We present an analysis, based on realistic assumptions about low-level vision, that estimates the distribution of background colours and visual textures, and predicts the best camouflage. We present data from a field experiment that tests and supports our predictions, using artificial moth-like targets under bird predation. Additionally, we present analogous data for humans, under tightly controlled viewing conditions, searching for targets on a computer screen. These data show that, in the absence of predator learning, the best single camouflage pattern for heterogeneous backgrounds is the most probable sample.
Background
Clinical application of therapeutic drug monitoring (TDM) to optimise anti‐TNF therapies in patients with IBD depends upon target ranges.
Aims
To review methodology used to determine ...therapeutic ranges and critically compare and contrast its application to infliximab and adalimumab.
Methods
A systematic review was performed, and relevant literature was summarised and critically examined.
Results
Upper limits of the therapeutic range are determined by toxicity, a plateau response and cost. Lower limits are determined by optimal concentration on the target of action in vitro and/or in vivo, or by correlation of drug levels with clinical efficacy using area‐under‐receiver‐operator‐curve (AUROC) analysis. In 43 studies, there were huge variations in time at which infliximab and adalimumab levels were measured, the end‐points used (clinical remission to mucosal healing), the clinical setting (active disease vs maintenance phase) and the reason for TDM (proactive vs reactive). In the maintenance phase for infliximab, lower trough limits 2.8‐5.7 µg/mL are reported depending upon end‐points used, with consistent AUROC 0.68‐0.77. Adalimumab TDM targets are even less consistent with a lower limit 5.9‐11.8 µg/mL (AUROC 0.66‐0.83) in some studies, but no cut‐off can be identified that is significantly associated with outcome in others, related to inherent pharmacokinetic and pharmacodynamic differences, and heterogeneity of study design.
Conclusions
Evidence for exposure‐response relationship is stronger for infliximab than adalimumab. Due to heterogeneity in settings for drug level measurements, therapeutic ranges vary. These factors need to be taken into account when interpreting the evidence and extending this to therapeutic strategies for IBD patients.
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