We have synthesized a 582,970-base pair Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection. To identify the genome as synthetic, we inserted "watermarks" at intergenic sites known to tolerate transposon insertions. Overlapping "cassettes" of 5 to 7 kilobases (kb), assembled from chemically synthesized oligonucleotides, were joined by in vitro recombination to produce intermediate (...) assemblies of approximately 24 kb, 72 kb ("1/8 genome"), and 144 kb ("1/4 genome"), which were all cloned as bacterial artificial chromosomes in Escherichia coli. Most of these intermediate clones were sequenced, and clones of all four 1/4 genomes with the correct sequence were identified. The complete synthetic genome was assembled by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae, then isolated and sequenced. A clone with the correct sequence was identified. The methods described here will be generally useful for constructing large DNA molecules from chemically synthesized pieces and also from combinations of natural and synthetic DNA segments. 10.1126/science.1151721. (shrink)
An edited version of a semi-autobiographical piece that Terence Hutchison wrote in 2001?2003, shortly before his death, in which he reflected on the methodological developments in which he had been involved, centred on the London School of Economics, in the 1930s. It explains very clearly the context out of which his own work arose. Particular attention is paid to the work of Lionel Robbins, Frank Knight and the philosopher Felix Kaufmann.
This paper raises questions about the epistemological foundations of evidence-based medicine . We argue that EBM is based upon reliabilist epistemological assumptions, and that this is appropriate - we should focus on identifying the most reliable processes for generating and collecting medical knowledge. However, we note that this should not be reduced to narrow questions about which research methodologies are the best for gathering evidence. Reliable processes for generating medical evidence might lie outside of formal research methods. We also question (...) the notion of the knower that is assumed by EBM. We argue that EBM assumes an enlightenment conception of knowers as autonomous, substitutable individuals. This conception is troubled by the way that clinicians learn the role of anecdote in health care and the role of patient choice, all of which bring into play features of clinicians and patients as situated individuals with particular backgrounds and experiences. EBM's enlightenment conception of the knower is also troubled by aspects of the way evidence is produced. Given these limitations, we argue that EBM should retain its reliabilist bent, but should look beyond formal research methodologies in identifying processes that yield reliable evidence for clinical practice. We suggest looking to feminist epistemology, with its focus on the standpoints of individual situated knowers, and the role of social context in determining what counts as knowledge. (shrink)
Surgical innovation promises improvements in healthcare, but it also raises ethical issues including risks of harm to patients, conflicts of interest and increased injustice in access to health care. In this article, we focus on risks of injustice, and use a case study of robotic prostatectomy to identify features of surgical innovation that risk introducing or exacerbating injustices. Interpreting justice as encompassing matters of both efficiency and equity, we first examine questions relating to government decisions about whether to publicly fund (...) access to innovative treatments. Here the case of robotic prostatectomy exemplifies the difficulty of accommodating healthcare priorities such as improving the health of marginalized groups. It also illustrates challenges with estimating the likely long-term costs and benefits of a new intervention, the difficulty of comparing outcomes of an innovative treatment to those of established treatments, and the further complexity associated with patient and surgeon preferences. Once the decision has been made to fund a new procedure, separate issues of justice arise at the level of providing care to individual patients. Here, the case of robotic prostatectomy exemplifies how features of surgical innovation, such as surgeon learning curves and the need for an adequate volume of cases at a treatment centre, can exacerbate injustices associated with treatment cost and the logistics of travelling for treatment. Drawing on our analysis, we conclude by making a number of recommendations for the just introduction of surgical innovations. (shrink)
We examined unconscious priming in a stem-completion task with both identity and form-related primes. Participants were given exclusion instructions to avoid completing a stem with a briefly flashed masked word . In Experiment 1, priming of around 7% occurred for both identity and form-based primes at a 33 ms exposure duration. When examining only trials in which the participants failed to identify the prime, this effect increased to 12% for identity primes, but remained the same for form-based primes. In Experiment (...) 2, priming without prime identification was 9% for identity primes, 4% for homophone primes, and 3% for orthographic control primes. Although identity priming was greater than form priming in both experiments, regression analyses revealed that orthographic and phonological overlap alone between the flashed primes and targets could completely account for unconscious identity priming. Hence, we conclude that masked words may only activate their sublexical orthographic and phonological representations and not their lexical representations. (shrink)
This paper rejects a traditional epistemic interpretation of conditional probability. Suppose some chance process produces outcomes X, Y,..., with probabilities P(X), P(Y),... If later observation reveals that outcome Y has in fact been achieved, then the probability of outcome X cannot normally be revised to P(X|Y) ['P&Y)/P(Y)]. This can only be done in exceptional circumstances - when more than just knowledge of Y-ness has been attained. The primary reason for this is that the weight of a piece of evidence varies (...) with the means by which it is provided, so knowledge of Y-ness does not have uniform impact on the probability of X. A better updating of the probability of X is provided by P(X|Y*), where Y* is not an outcome of the chance process being observed, but the sentence 'the outcome Y has been observed', an 'outcome' of the subsequent observation process. This alternative formula is widely endorsed in practice, but not well recognized in theory, where the oversight has generated some unsatisfactory consequences. (shrink)
Three experiments examined the role of response criteria in a masked semantic priming paradigm using an exclusion task. Experiment 1 used on-line prime-report and exclusion instructions in which participants were told to avoid completing a word stem with a word related to a prime flashed for 0, 38 or 212 ms. Semantic priming was significant in the items analysis, but was moderated by peoples’ ability to report the prime in the participant analysis. Prime-report thresholds in Experiment 2 were made more (...) liberal by instructing participants to guess on every trial. Prime-report increased from Experiment 1 as exclusion failures were eliminated. Experiment 3 clarified the relationship between awareness and prime identification using an on-line measure of confidence and different liberal prime report instructions. The current findings suggest that the ability to act upon and report information in a masked prime is determined by a variable response criterion, which can be manipulated as an independent variable. (shrink)
OBJECTIVES: This article presents an original definition of surgical innovation and a practical tool for identifying planned innovations. These will support the responsible introduction of surgical innovations. BACKGROUND: Frameworks developed for the safer introduction of surgical innovations rely upon identifying cases of innovation; oversight cannot occur unless innovations are identified. However, there is no consensus among surgeons about which interventions they consider innovative; existing definitions are vague and impractical. METHODS: Using conceptual analysis, this article synthesizes findings from relevant literature, and (...) from qualitative research with surgeons, to develop an original definition of surgical innovation and a tool for prospectively identifying planned surgical innovations. The tool has been developed in light of feedback from health care professionals, surgeons, and policy makers. RESULTS: This definition of innovation distinguishes between variations, introduction of established interventions, and innovations in surgical techniques or use of devices. It can be applied easily and consistently, is sensitive to the key features of innovation, is prospective, and focuses on features relevant to safety and evaluation. The accompanying tool is deliberately broad so that appropriate supports may, if necessary, be provided each time that a surgeon does something "new". CONCLUSIONS: The definition presented in this article overcomes a number of practical challenges. The definition and tool will be of value in supporting responsible surgical innovation, in particular, through the prospective identification of planned innovations. (shrink)
Discussions of the Tylenol and Exxon Valdez cases found in textbooks, public relations scholarship, and news coverage are assessed to understand the meanings that practitioners, educators, critics, and journalists have attributed to those events. The essay objects to a central claim made by critics who say these cases set standards for ethical behavior in public relations. This claim, according to us, mistakes moral drama for ethical deliberation.
This paper argues against a standard view that all deterministic and conservative classical mechanical systems are time-reversible, by asking how the temporal evolution of a system modulates parametric imprecision (either ontological or epistemic). It notes that well-behaved systems (e.g. inertial motion) can possess a dynamics which is unstable enough to fail at reversing uncertainties—even though exact values are reliably reversed. A limited (but significant) source of irreversibility is thus displayed in classical mechanics, closely analogous the lack of predictability revealed by (...) unstable chaotic systems. (shrink)
For over two centuries since the first emergence of modern political economy, right down to the early decade of the 20th century, there were leading or important economists, who were also leading or important philosophers: Locke, Hume, Smith, J.S. Mill, Jevons, and Sidgwick and the Keynes's are a few obvious examples. The essential philosophical and methodological problems of the subject could be, and were, authoritatively addressed. And inspite of profound and lasting methodological disagreements, a relatively broad, workable, mainstream consensus, particularly (...) in the Anglophone world, was more or less adequately maintained among the comparatively very small number cultivating the subject. The state of affairs has been profoundly shattered, roughly in the last two-thirds of this century.The huge increase in numbers has brought the rise of departmental barriers, accompanied by a narrow ?professionalism? among mainstream economists, which rejects philosophical and methodological clarity as outside their intellectual responsibilities. A second part of this paper will discuss what kinds of philosophical-methodological problems economists should address. (shrink)
Patient or public involvement in health research is increasingly expected as a matter of policy. In theory, PPI can contribute both to the epistemic aims intrinsic to research, and to extrinsically valued features of research such as social inclusion and transparency. In practice, the aims of PPI have not always been clear, although there has been a tendency to encourage the involvement of so-called ordinary people who are regarded as representative of an assumed patient perspective. In this paper we focus (...) on the epistemic potential of PPI, using theoretical work in epistemology to develop a nuanced account of patients’ experiential knowledge and how this might contribute directly to conceptual development, hypothesis generation and data interpretation. We also consider how some features of health research pose barriers to this kind of epistemic contribution. Drawing on Miranda Fricker’s idea of testimonial injustice, we explore how disciplinary indicators of credibility in clinical and academic health research contexts might be wrongly applied to those involved in PPI, undermining their potential to contribute. Finally we argue for a range of strategies to maximize opportunities for patients to engage with research teams and make epistemologically significant contributions to research. (shrink)
We consider here an important family of conditional bets, those that proceed to settlement if and only if some agreed evidence is received that a condition has been met. Despite an opinion widespread in the literature, we observe that when the evidence is strong enough to generate certainty as to whether the condition has been met or not, using traditional conditional probabilities for such bets will NOT preserve a gambler from having a synchronic Dutch Book imposed upon him. On the (...) contrary (I show) the gambler can be Dutch-Booked if his betting ratios ever depart from a rather different probability, one that involves the probability of the agreed evidence being provided. We note furthermore that this same alternative probability assessment is necessary if the evidence is weaker (i.e. if it fails to provide knowledge whether or not the condition has been met.) By contrast, some of the (rather different) probability assessments proposed by Jeffrey, precisely for such situations, still expose the gambler to a Dutch-Book. (shrink)
In the history of thermodynamics, two dates stand out as especially important: 1824, when Sadi Carnot's brilliant memoir Réflexions sur la puissance motrice du feu appeared in print; and 1850, when Rudolf Clausius published his similarly titled paper ‘Ueber die bewegende Kraft der Wärme’. In this paper Clausius narrowly beat the Scottish physicist William Thomson to the solution of a puzzle which had been highlighted in the latter's recent publications: how could Carnot's theory, with all its intellectual attractions, be reconciled (...) with the newly discovered principle of the inter-convertibility of heat and work? Clausius's solution was to replace Carnot's axiom of heat conservation, with the axiom now known as the second law of thermodynamics. (shrink)