Time-resolved fast-neutron imaging with a pulse-counting image intensifier

A new imaging method that combines high-efficiency fast-neutron detection with sub-ns time resolution is presented. This is achieved by exploiting the high neutron detection efficiency of a thick scintillator and the fast timing capability and flexibility of light-pulse detection with a dedicated image intensifier. The neutron converter is a plastic scintillator slab or, alternatively, a scintillating fibre screen. The scintillator is optically coupled to a pulse counting image intensifier which measures the 2-dimensional position coordinates and the Time-Of-Flight (TOF) of each detected neutron with an intrinsic time resolution of less than 1 ns. Large-area imaging devices with high count rate capability can be obtained by lateral segmentation of the optical readout channels

Popular Conceptions of Nationhood in Old and New European Member States: Partial Support for the Ethnic-Civic Framework

One of the most influential theories in the study of nationalism has been the ethnic-East/civic-West framework developed by Hans Kohn. Using the 2002 Eurobarometer survey on national identity and building on earlier survey studies, this article examines whether the Kohn framework is valid at the level of popular understandings of nationhood. It scrutinizes the framework both conceptually - do people define nationhood in civic or ethnic terms? - and regionally - is the East indeed more ethnic than the West and the West more civic than the East? It will show that identity markers cluster in a political, a cultural and an ethnic dimension. Respondents do not see these dimensions as competing sources of nationhood, however. The article further lends some support for the regional component of the framework. Lastly, it argues that it is the intensity of national identifications rather than their qualitative nature (ethnic-civic) that correlates with xenophobia. © 2006 Taylor & Francis

Tracking individual nanodiamonds in Drosophila melanogaster embryos

Tracking the dynamics of fluorescent nanoparticles during embryonic development allows insights into the physical state of the embryo and, potentially, molecular processes governing developmental mechanisms. In this work, we investigate the motion of individual fluorescent nanodiamonds micro-injected into Drosophila melanogaster embryos prior to cellularisation. Fluorescence correlation spectroscopy and wide-field imaging techniques are applied to individual fluorescent nanodiamonds in blastoderm cells during stage 5 of development to a depth of ~40 \mu m. The majority of nanodiamonds in the blastoderm cells during cellularisation exhibit free diffusion with an average diffusion coefficient of (6 $\pm$ 3) x 10$^{-3}$ \mu m$^2$/s, (mean $\pm$ SD). Driven motion in the blastoderm cells was also observed with an average velocity of 0.13 $\pm$ 0.10 \mu m/s (mean $\pm$ SD) \mu m/s and an average applied force of 0.07 $\pm$ 0.05 pN (mean $\pm$ SD). Nanodiamonds in the periplasm between the nuclei and yolk were also found to undergo free diffusion with a significantly larger diffusion coefficient of (63 $\pm$ 35) x10$^{-3}$ \mu m$^2$/s (mean $\pm$ SD). Driven motion in this region exhibited similar average velocities and applied forces compared to the blastoderm cells indicating the transport dynamics in the two cytoplasmic regions are analogous.Comment: 20 pages, 6 figure

Can perioperative pCO2 gaps predict complications in patients undergoing major elective abdominal surgery randomized to goal-directed therapy or standard care? A secondary analysis

The difference between venous and arterial carbon dioxide pressure (pCO2 gap), has been used as a diagnostic and prognostic tool. We aimed to assess whether perioperative pCO2 gaps can predict postoperative complications. This was a secondary analysis of a multicenter RCT comparing goal-directed therapy (GDT) to standard care in which 464 patients undergoing high-risk elective abdominal surgery were included. Arterial and central venous blood samples were simultaneously obtained at four time points: after induction, at the end of surgery, at PACU/ICU admission, and PACU/ICU discharge. Complications within the first 30 days after surgery were recorded. Similar pCO2 gaps were found in patients with and without complications, except for the pCO2 gap at the end of surgery, which was higher in patients with complications (6.0 mmHg [5.0–8.0] vs. 6.0 mmHg [4.1–7.5], p = 0.005). The area under receiver operating characteristics curves for predicting complications from pCO2 gaps at all time points were between 0.5 and 0.6. A weak correlation between ScvO2 and pCO2 gaps was found for all timepoints (ρ was between − 0.40 and − 0.29 for all timepoints, p < 0.001). The pCO2 gap did not differ between GDT and standard care at any of the selected time points. In our study, pCO2 gap was a poor predictor of major postoperative complications at all selected time points. Our research does not support the use of pCO2 gap as a prognostic tool after high-risk abdominal surgery. pCO2 gaps were comparable between GDT and standard care. Clinical trial registration Netherlands Trial Registry NTR3380

ISRCTN12125882 - Influence of topical anti-VEGF (Ranibizumab) on the outcome of filtration surgery for glaucoma - Study Protocol

<p>Abstract</p> <p>Background</p> <p>Excessive wound healing, with scarring of the episcleral tissue or encapsulation of the filtering bleb is the main reason for failure in trabeculectomy. Ranibizumab, an inhibitor of the Vascular Endothelial Growth Factor (VEGF), is seen as a promising candidate to prevent or treat extensive wound healing. We describe the design of a two phased study, i) assessing the local tolerability and safety of topical ranibizumab and ii) assessing the efficacy of topical ranibizumab against placebo in patients who underwent trabeculectomy with mitomycin C combined with phacoemulsification and intra ocular lens (IOL) implantation.</p> <p>Methods/Design</p> <p>In the first phase five patients that had trabeculectomy with mitomycin C combined with phacoemulsification and IOL implantation will be treated with topical ranibizumab (Lucentis^®) eye drops (2 mg/ml) four times daily for one month. The treatment will be started at the first postoperative day. Patients will be assessed for local and systemic side effects using a standardised schedule. In the second phase, after successful completion of phase 1, consenting eligible patients who underwent trabeculectomy with mitomycin C combined with phacoemulsification and IOL implantation will be randomised to either receive topical ranibizumab eye drops (2 mg/ml) four times daily for 1 month or placebo (BSS 4x/d for 1 month). Patients will be reviewed weekly for 4 weeks until conjunctival sutures are removed. Further follow up examinations are planned after 3 and six months. Assessment of differences in the intraocular eye pressure will be considered primary, and bleb appearance/vascularisation using a standardized photography and the Moorfields bleb grading system, postoperative intraocular pressure and conjunctival wound healing problems will be considered secondary outcome parameters.</p> <p>Discussion</p> <p>Anti-VEGF-antibodies might be more effective in preventing scaring and might have fewer toxic side effects than the currently used anti-metabolites and may replace them in the long term.</p> <p>Trial Registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN12125882">ISRCTN12125882</a></p

Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data

OBJECTIVE: To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. DESIGN: Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. DATA SOURCES: Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. RESULTS: Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). CONCLUSIONS: In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012002780

In search of the authentic nation: landscape and national identity in Canada and Switzerland

While the study of nationalism and national identity has flourished in the last decade, little attention has been devoted to the conditions under which natural environments acquire significance in definitions of nationhood. This article examines the identity-forming role of landscape depictions in two polyethnic nation-states: Canada and Switzerland. Two types of geographical national identity are identified. The first – what we call the ‘nationalisation of nature’– portrays zarticular landscapes as expressions of national authenticity. The second pattern – what we refer to as the ‘naturalisation of the nation’– rests upon a notion of geographical determinism that depicts specific landscapes as forces capable of determining national identity. The authors offer two reasons why the second pattern came to prevail in the cases under consideration: (1) the affinity between wild landscape and the Romantic ideal of pure, rugged nature, and (2) a divergence between the nationalist ideal of ethnic homogeneity and the polyethnic composition of the two societies under consideration

Autologous humanized PDX modeling for immuno-oncology recapitulates features of the human tumor microenvironment.

BACKGROUND: Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by interspecies differences between human and mouse, as well as inter-person germline and somatic variation. To address these gaps, we developed an autologous system that models the tumor microenvironment (TME) from individual patients with solid tumors. METHOD: With patient-derived bone marrow hematopoietic stem and progenitor cells (HSPCs), we engrafted a patient\u27s hematopoietic system in MISTRG6 mice, followed by transfer of patient-derived xenograft (PDX) tissue, providing a fully genetically matched model to recapitulate the individual\u27s TME. We used this system to prospectively study tumor-immune interactions in patients with solid tumor. RESULTS: Autologous PDX mice generated innate and adaptive immune populations; these cells populated the TME; and tumors from autologously engrafted mice grew larger than tumors from non-engrafted littermate controls. Single-cell transcriptomics revealed a prominent vascular endothelial growth factor A (VEGFA) signature in TME myeloid cells, and inhibition of human VEGF-A abrogated enhanced growth. CONCLUSIONS: Humanization of the interleukin 6 locus in MISTRG6 mice enhances HSPC engraftment, making it feasible to model tumor-immune interactions in an autologous manner from a bedside bone marrow aspirate. The TME from these autologous tumors display hallmarks of the human TME including innate and adaptive immune activation and provide a platform for preclinical drug testing

Jimmy Swaggart's Secular Confession

This is the author's accepted manuscript. The published version is available from http://dx.doi.org/10.1080/02773940902766748 .Following the exposure of televangelist Jimmy Swaggart’s illicit rendezvous with a New Orleans prostitute, the Assemblies of God simultaneously orchestrated a massive attempt to silence those who would discuss the tryst and arranged the most widely publicized confession in American history theretofore. The coincidence of a “silence campaign” with the vast distribution of a public confession invites us to reconsider the nature of the public confession. For what place has a public confession, the discourse of disclosure par excellence, in a silence campaign? This question is best answered, I argue, if we understand public confession not as a stable a-historical form, but as a practice that is informed by multiple, competing traditions. I argue that by situating Swaggart’s performance in a philosophically modern and secular tradition of public confession we can understand both its complicity in a silence campaign and, more generally, the political logic of the modern public confession