Pharmacokinetics of 111In-labeled OC-125 antibody in cancer patients compared with the 19-9 antibody

We recently reported on the pharmacokinetics in 14 cancer patients of the 19-9 antibody radiolabeled with 111In. We have now repeated this investigation in 18 cancer patients using the OC-125 antibody, in part to compare the in vivo behavior of two murine monoclonal antibodies of the same subclass administered as the F(ab\u27)2 fragments, by the same route and at the same dose. As in the earlier investigation, 1 mg of fragments was infused i.v., and organ quantitation was obtained for up to 72 h along with frequent blood and urine samples for chromatographic evaluation. Analysis of urine showed that activity clearance by this route amounted to 0.29%/h and consisted of labeled DTPA only in early samples and metabolic products thereafter. Analysis of serum samples often showed the presence of a high-molecular-weight species appearing within 24 h. This species is probably due to antibody binding to circulating antigen, although the percentage of circulating activity present as this species did not correlate well with circulating antigen levels. As before, organ accumulation was greatest in the liver, although levels were significantly reduced (12% compared to 20% of administered dose at 24 h, P less than 0.01). Plasma clearance was also significantly different: whereas the label in the case of the OC-125 antibody showed one-compartment clearance kinetics and remained in the plasma compartment, in the 19-9 case the label diffused to a second, unidentified compartment

Recycling bins, garbage cans or think tanks? Three myths regarding policy analysis institutes

The phrase 'think tank' has become ubiquitous – overworked and underspecified – in the political lexicon. It is entrenched in scholarly discussions of public policy as well as in the 'policy wonk' of journalists, lobbyists and spin-doctors. This does not mean that there is an agreed definition of think tank or consensual understanding of their roles and functions. Nevertheless, the majority of organizations with this label undertake policy research of some kind. The idea of think tanks as a research communication 'bridge' presupposes that there are discernible boundaries between (social) science and policy. This paper will investigate some of these boundaries. The frontiers are not only organizational and legal; they also exist in how the 'public interest' is conceived by these bodies and their financiers. Moreover, the social interactions and exchanges involved in 'bridging', themselves muddy the conception of 'boundary', allowing for analysis to go beyond the dualism imposed in seeing science on one side of the bridge, and the state on the other, to address the complex relations between experts and public policy

Rapid rest/stress regadenoson ungated perfusion CMR for detection of coronary artery disease in patients with atrial fibrillation.

Cardiovascular magnetic resonance (CMR) perfusion has been established as a useful imaging modality for the detection of coronary artery disease (CAD). However, there are several limitations when applying standard, ECG-gated stress/rest perfusion CMR to patients with atrial fibrillation (AF). In this study we investigate an approach with no ECG gating and a rapid rest/stress perfusion protocol to determine its accuracy for detection of CAD in patients with AF. 26 patients with AF underwent a rapid rest/regadenoson stress CMR perfusion imaging protocol, and all patients had X-ray coronary angiography. An ungated radial myocardial perfusion sequence was used. Imaging protocol included: rest perfusion image acquisition, followed nearly immediately by administration of regadenoson to induce hyperemia, 60 s wait, and stress image acquisition. CMR perfusion images were interpreted by three blinded readers as normal or abnormal. Diagnostic accuracy was evaluated by comparison to X-ray angiography. 21 of the CMR rest/stress perfusion scans were negative, and 5 were positive by angiography criteria. Majority results of the ungated datasets from all of the readers showed a sensitivity, specificity and accuracy of 80, 100 and 96%, respectively, for detection of CAD. An ungated, rapid rest/stress regadenoson perfusion CMR protocol appears to be useful for the diagnosis of obstructive CAD in patients with AF

Political computational thinking:policy networks, digital governance and ‘learning to code’

Reflecting political shifts toward both ‘network governance' and ‘digital governance', the idea of ‘learning to code' has become part of a major reform agenda in education policy in England. This article provides a ‘policy network analysis' tracing the governmental, business and civil society actors now operating in policy networks to project learning to code into the reformed programs of study for computing in the National Curriculum in England. The insertion of learning to code into the curriculum provides evidence of how the education policy process is being displaced to cross-sector ‘boundary organizations' such as ‘policy labs' that act as connecting nodes to broker networks across public and private sector borderlines. It also examines how the pedagogies of learning to code are intended to inculcate young people into the material practices and systems of thought associated with computer coding, and to contribute to new forms of ‘digital governance'. These developments are evidence of a ‘reluctant state' deconcentrating its responsibilities, and also of a computational style of political thinking that assumes policy problems can be addressed using the right code. Learning to code is seen as a way of shaping governable citizens that can participate in the dynamics of digital governance

‘I know my rights, but am I better off?’: institutions and disability in Uganda

Uganda is internationally recognised for both its legal and constitutional provisions for people with disabilities, and the presence of disabled persons’ organisations that provide informal advocacy and support. Using a unique dataset of 579 Ugandans with physical disabilities, we develop a conceptual framework on social capital to investigate the factors correlated with knowledge of formal institutions that target disability. In examining whether this knowledge results in higher incomes we find that gender matters. A woman’s education and membership of external networks are correlates of knowledge; higher levels of this knowledge are associated with substantially higher levels of income

BOUT++ : Recent and current developments

BOUT++ is a 3D nonlinear finite-difference plasma simulation code, capable of solving quite general systems of PDEs, but targeted particularly on studies of the edge region of tokamak plasmas. BOUT++ is publicly available, and has been adopted by a growing number of researchers worldwide. Here we present improvements which have been made to the code since its original release, both in terms of structure and its capabilities. Some recent applications of these methods are reviewed, and areas of active development are discussed. We also present algorithms and tools which have been developed to enable creation of inputs from analytic expressions and experimental data, and for processing and visualisation of output results. This includes a new tool Hypnotoad for the creation of meshes from experimental equilibria. Algorithms have been implemented in BOUT++ to solve a range of linear algebraic problems encountered in the simulation of reduced MHD and gyro-fluid models: A preconditioning scheme is presented which enables the plasma potential to be calculated efficiently using iterative methods supplied by the PETSc library, without invoking the Boussinesq approximation. Scaling studies are also performed of a linear solver used as part of physics-based preconditioning to accelerate the convergence of implicit time-integration schemes

Empathy, engagement, entrainment: the interaction dynamics of aesthetic experience

A recent version of the view that aesthetic experience is based in empathy as inner imitation explains aesthetic experience as the automatic simulation of actions, emotions, and bodily sensations depicted in an artwork by motor neurons in the brain. Criticizing the simulation theory for committing to an erroneous concept of empathy and failing to distinguish regular from aesthetic experiences of art, I advance an alternative, dynamic approach and claim that aesthetic experience is enacted and skillful, based in the recognition of others’ experiences as distinct from one’s own. In combining insights from mainly psychology, phenomenology, and cognitive science, the dynamic approach aims to explain the emergence of aesthetic experience in terms of the reciprocal interaction between viewer and artwork. I argue that aesthetic experience emerges by participatory sense-making and revolves around movement as a means for creating meaning. While entrainment merely plays a preparatory part in this, aesthetic engagement constitutes the phenomenological side of coupling to an artwork and provides the context for exploration, and eventually for moving, seeing, and feeling with art. I submit that aesthetic experience emerges from bodily and emotional engagement with works of art via the complementary processes of the perception–action and motion–emotion loops. The former involves the embodied visual exploration of an artwork in physical space, and progressively structures and organizes visual experience by way of perceptual feedback from body movements made in response to the artwork. The latter concerns the movement qualities and shapes of implicit and explicit bodily responses to an artwork that cue emotion and thereby modulate over-all affect and attitude. The two processes cause the viewer to bodily and emotionally move with and be moved by individual works of art, and consequently to recognize another psychological orientation than her own, which explains how art can cause feelings of insight or awe and disclose aspects of life that are unfamiliar or novel to the viewer

The Finnish Think Tank Landscape : A Mixture of Consensualism and Adversity?

As a common feature of Nordic countries, the Finnish landscape of thinks tanks has been populated by large corporatist interest organisations and government-funded research organisations. In addition to this, since 2005, party-affiliated think tanks form a notable part of the picture. Recently, several small think tanks that are oriented towards specific themes, such as international relations, the environment and feminism, have been founded. This article examines Finnish developments in the field of think tanks with two objectives. First, it gives a general overview of the Finnish think tank landscape. Second, by using interview data and public mission statements of the most prominent think tanks, it explores how these organisations see their role in Finnish society. What is their relationship with media and the political machinery, and how does this relate to their position and activities as either consensual or adversarial actors? It is concluded that redeeming the place of think tanks in the Finnish polity is a continuing challenge, and resorting to adversarial tactics is not a favourable way to do so. This approach has mostly been attempted by neoliberal think tanks that, in the past, have also profited from corporatist structures to enhance their objectives.Peer reviewe

Rapid automatic segmentation of abnormal tissue in late gadolinium enhancement cardiovascular magnetic resonance images for improved management of long-standing persistent atrial fibrillation

Background: Atrial fibrillation (AF) is the most common heart rhythm disorder. In order for late Gd enhancement cardiovascular magnetic resonance (LGE CMR) to ameliorate the AF management, the ready availability of the accurate enhancement segmentation is required. However, the computer-aided segmentation of enhancement in LGE CMR of AF is still an open question. Additionally, the number of centres that have reported successful application of LGE CMR to guide clinical AF strategies remains low, while the debate on LGE CMR’s diagnostic ability for AF still holds. The aim of this study is to propose a method that reliably distinguishes enhanced (abnormal) from non-enhanced (healthy) tissue within the left atrial wall of (pre-ablation and 3 months post-ablation) LGE CMR data-sets from long-standing persistent AF patients studied at our centre. Methods: Enhancement segmentation was achieved by employing thresholds benchmarked against the statistics of the whole left atrial blood-pool (LABP). The test-set cross-validation mechanism was applied to determine the input feature representation and algorithm that best predict enhancement threshold levels. Results: Global normalized intensity threshold levels T PRE = 1 1/4 and T POST = 1 5/8 were found to segment enhancement in data-sets acquired pre-ablation and at 3 months post-ablation, respectively. The segmentation results were corroborated by using visual inspection of LGE CMR brightness levels and one endocardial bipolar voltage map. The measured extent of pre-ablation fibrosis fell within the normal range for the specific arrhythmia phenotype. 3D volume renderings of segmented post-ablation enhancement emulated the expected ablation lesion patterns. By comparing our technique with other related approaches that proposed different threshold levels (although they also relied on reference regions from within the LABP) for segmenting enhancement in LGE CMR data-sets of AF patients, we illustrated that the cut-off levels employed by other centres may not be usable for clinical studies performed in our centre. Conclusions: The proposed technique has great potential for successful employment in the AF management within our centre. It provides a highly desirable validation of the LGE CMR technique for AF studies. Inter-centre differences in the CMR acquisition protocol and image analysis strategy inevitably impede the selection of a universally optimal algorithm for segmentation of enhancement in AF studies