Power considerations towards a sustainable pan-european network

Energy savings are observed and quantified in the Pan-European network using transparent optical network technology. The network was dimensioned, using realistic traffic predictions of the optical networking roadmap of the European project BONE

Tests for predicting complications of pre-eclampsia: A protocol for systematic reviews

Background Pre-eclampsia is associated with several complications. Early prediction of complications and timely management is needed for clinical care of these patients to avert fetal and maternal mortality and morbidity. There is a need to identify best testing strategies in pre eclampsia to identify the women at increased risk of complications. We aim to determine the accuracy of various tests to predict complications of pre-eclampsia by systematic quantitative reviews. Method We performed extensive search in MEDLINE (1951–2004), EMBASE (1974–2004) and also will also include manual searches of bibliographies of primary and review articles. An initial search has revealed 19500 citations. Two reviewers will independently select studies and extract data on study characteristics, quality and accuracy. Accuracy data will be used to construct 2 × 2 tables. Data synthesis will involve assessment for heterogeneity and appropriately pooling of results to produce summary Receiver Operating Characteristics (ROC) curve and summary likelihood ratios. Discussion This review will generate predictive information and integrate that with therapeutic effectiveness to determine the absolute benefit and harm of available therapy in reducing complications in women with pre-eclampsia

The relationship between tooth size discrepancy and archform classification in orthodontic patients

Background: To determine the relationship between clinically significant tooth size discrepancies (TSD) and archform classification in orthodontic patients. Material and Methods: Two hundred and forty consecutive sets of pre-treatment orthodontic study models were scanned and landmarked. All models had permanent teeth erupted from first molar to first molar in both arches. Sixty sets of images were classified into two groups of 30 according to the presence (group 1) or absence (group 2) of a clinically significant overall or anterior TSD (>2 SD from Bolton’s original means). Mean upper and lower archforms were created for each group using a fourth degree polynomial curve. Upper and lower archforms in each group were classified as square, tapering or ovoid; their distribution was analysed using the Fisher test with a 5% level of significance. To evaluate the intra-operator error when determining archform type, the 60 archforms were re-classified by the same operator two weeks later. The unweighted Kappa statistic at 95% confidence intervals was used to determine the similarity of the classification on the two occasions. Results: Reproducibility of the classification of archform was very good (unweighted Kappa statistic of 0.83 with a 95% confidence interval of 0.73, 0.93). There was no statistically significant difference in the distribution of archform type between group 1 and group 2 for the upper ( p =0.3305) or lower ( p =0.6310) arches. Conclusions: The presence of a clinically significant TSD and archform classification do not appear to be related

Confined crystallization of fenofibrate in nanoporous silica

Producing stable nanocrystals confined to porous excipient media is a desirable way to increase the dissolution rate and improve the bioavailability of poorly water soluble pharmaceuticals. The poorly soluble pharmaceutical fenofibrate was crystallized in controlled pore glass (CPG) of 10 different pore sizes between 12 nm and 300 nm. High drug loadings of greater than 20 wt% were achieved across all pore sizes greater than 20 nm. Nanocrystalline fenofibrate was formed in pore sizes greater than 20 nm and showed characteristic melting point depressions following a Gibbs–Thomson relationship as well as enhanced dissolution rates. Solid-state Nuclear Magnetic Resonance (NMR) was employed to characterize the crystallinity of the confined molecules. These results help to advance the fundamental understanding of nanocrystallization in confined pores.Novartis-MIT Center for Continuous ManufacturingNational Institute for Biomedical Imaging and Bioengineering (U.S.) (Grant EB-002026)Natural Sciences and Engineering Research Council of Canada (Banting Postdoctoral Fellowship

Development and face validation of strategies for improving consultation skills

While formative workplace based assessment can improve learners' skills, it often does not because the procedures used do not facilitate feedback which is sufficiently specific to scaffold improvement. Provision of pre-formulated strategies to address predicted learning needs has potential to improve the quality and automate the provision of written feedback. To systematically develop, validate and maximise the utility of a comprehensive list of strategies for improvement of consultation skills through a process involving both medical students and their clinical primary and secondary care tutors. Modified Delphi study with tutors, modified nominal group study with students with moderation of outputs by consensus round table discussion by the authors. 35 hospital and 21 GP tutors participated in the Delphi study and contributed 153 new or modified strategies. After review of these and the 205 original strategies, 265 strategies entered the nominal group study to which 46 year four and five students contributed, resulting in the final list of 249 validated strategies. We have developed a valid and comprehensive set of strategies which are considered useful by medical students. This list can be immediately applied by any school which uses the Calgary Cambridge Framework to inform the content of formative feedback on consultation skills. We consider that the list could also be mapped to alternative skills frameworks and so be utilised by schools which do not use the Calgary Cambridge Framework

Hydrodynamic gene delivery in human skin using a hollow microneedle device

Microneedle devices have been proposed as a minimally invasive delivery system for the intradermal administration of nucleic acids, both plasmid DNA (pDNA) and siRNA, to treat localised disease or provide vaccination. Different microneedle types and application methods have been investigated in the laboratory, but limited and irreproducible levels of gene expression have proven to be significant challenges to pre-clinical to clinical progression. This study is the first to explore the potential of a hollow microneedle device for the delivery and subsequent expression of pDNA in human skin. The regulatory approved MicronJet600® (MicronJet hereafter) device was used to deliver reporter plasmids (pCMVβ and pEGFP-N1) into viable excised human skin. Exogenous gene expression was subsequently detected at multiple locations that were distant from the injection site but within the confines of the bleb created by the intradermal bolus. The observed levels of gene expression in the tissue are at least comparable to that achieved by the most invasive microneedle application methods e.g. lateral application of a microneedle. Gene expression was predominantly located in the epidermis, although also evident in the papillary dermis. Optical coherence tomography permitted real time visualisation of the sub-surface skin architecture and, unlike a conventional intradermal injection, MicronJet administration of a 50 μL bolus appears to create multiple superficial microdisruptions in the papillary dermis and epidermis. These were co-localised with expression of the pCMVβ reporter plasmid. We have therefore shown, for the first time, that a hollow microneedle device can facilitate efficient and reproducible gene expression of exogenous naked pDNA in human skin using volumes that are considered to be standard for intradermal administration, and postulate a hydrodynamic effect as the mechanism of gene delivery

Optical properties of nanocrystalline ZnO thin films grown using pulsed laser deposition

Raman spectroscopy, x-ray diffractometry, atomic force microscopy, photoluminescence spectroscopy and reflectance spectroscopy have been used to characterize ZnO thin films grown by pulsed laser deposition as a function of the post-growth annealing temperature. Raman results show enhancement and broadening of certain Raman features which correlate with changes in the widths of the x-ray diffraction peaks for samples with varying grain size in the 50-100 nm range. These data suggest that electric fields, arising from charge trapping at grain boundaries, in conjunction with localised and surface phonon modes, are the cause of the intensity enhancement and asymmetry of the Raman features. Band-edge photoluminescence and reflectance spectra also altered considerably with increases in grain size, showing clearly observable excitonic structure in the reflectance spectra. An analysis using a deformation potential Hamiltonian demonstrates that the experimental exciton energies are not explicable solely in terms of sample strain and give additional evidence for electric fields in the samples due to charge trapping at grain boundaries. This is supported by theoretical estimates of the exciton energy perturbation due to electric fields and also by the behaviour of the green band in the samples. Detailed studies show that reflectance spectra in nanocrystalline ZnO differ substantially from bulk material. Interaction of excitons, damped by strong electric field effects, with photons leads to exciton-polaritons with substantial damping, eliminating the normal Fabry-Perot structure seen in thin films. Good qualitative agreement is achieved between the model and data and the conclusions are also in good agreement with the photoluminescence and Raman data. Finally, high intensity optical pumping data of these samples again shows a dependence on grain size. All samples show evidence of high excitation effects and the sample with the largest grain size displays random lasing at room temperature. All our results indicate the very strong influence of electric fields due to charge trapping at grain boundaries on the optical properties of nanocrystalline ZnO

Acquisition of pneumococci specific effector and regulatory Cd4+ T cells localising within human upper respiratory-tract mucosal lymphoid tissue

The upper respiratory tract mucosa is the location for commensal Streptococcus (S.) pneumoniae colonization and therefore represents a major site of contact between host and bacteria. The CD4(+) T cell response to pneumococcus is increasingly recognised as an important mediator of immunity that protects against invasive disease, with data suggesting a critical role for Th17 cells in mucosal clearance. By assessing CD4 T cell proliferative responses we demonstrate age-related sequestration of Th1 and Th17 CD4(+) T cells reactive to pneumococcal protein antigens within mucosal lymphoid tissue. CD25(hi) T cell depletion and utilisation of pneumococcal specific MHCII tetramers revealed the presence of antigen specific Tregs that utilised CTLA-4 and PDL-1 surface molecules to suppress these responses. The balance between mucosal effector and regulatory CD4(+) T cell immunity is likely to be critical to pneumococcal commensalism and the prevention of unwanted pathology associated with carriage. However, if dysregulated, such responses may render the host more susceptible to invasive pneumococcal infection and adversely affect the successful implementation of both polysaccharide-conjugate and novel protein-based pneumococcal vaccines

Estimation of proteinuria as a predictor of complications of pre-eclampsia: a systematic review

Background Proteinuria is one of the essential criteria for the clinical diagnosis of pre-eclampsia. Increasing levels of proteinuria is considered to be associated with adverse maternal and fetal outcomes. We aim to determine the accuracy with which the amount of proteinuria predicts maternal and fetal complications in women with pre-eclampsia by systematic quantitative review of test accuracy studies. Methods We conducted electronic searches in MEDLINE (1951 to 2007), EMBASE (1980 to 2007), the Cochrane Library (2007) and the MEDION database to identify relevant articles and hand-search of selected specialist journals and reference lists of articles. There were no language restrictions for any of these searches. Two reviewers independently selected those articles in which the accuracy of proteinuria estimate was evaluated to predict maternal and fetal complications of pre-eclampsia. Data were extracted on study characteristics, quality and accuracy to construct 2 × 2 tables with maternal and fetal complications as reference standards. Results Sixteen primary articles with a total of 6749 women met the selection criteria with levels of proteinuria estimated by urine dipstick, 24-hour urine proteinuria or urine protein:creatinine ratio as a predictor of complications of pre-eclampsia. All 10 studies predicting maternal outcomes showed that proteinuria is a poor predictor of maternal complications in women with pre-eclampsia. Seventeen studies used laboratory analysis and eight studies bedside analysis to assess the accuracy of proteinuria in predicting fetal and neonatal complications. Summary likelihood ratios of positive and negative tests for the threshold level of 5 g/24 h were 2.0 (95% CI 1.5, 2.7) and 0.53 (95% CI 0.27, 1) for stillbirths, 1.5 (95% CI 0.94, 2.4) and 0.73 (95% CI 0.39, 1.4) for neonatal deaths and 1.5 (95% 1, 2) and 0.78 (95% 0.64, 0.95) for Neonatal Intensive Care Unit admission. Conclusion Measure of proteinuria is a poor predictor of either maternal or fetal complications in women with pre-eclampsia