Pretreatment prognostic value of dynamic contrast-enhanced magnetic resonance imaging vascular, texture, shape, and size parameters compared with traditional survival indicators obtained from locally advanced breast cancer patients

Objectives: The aim of this study was to determine if associations exist between pretreatment dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI)-based metrics (vascular kinetics, texture, shape, size) and survival intervals. Furthermore, the aim of this study was to compare the prognostic value of DCE-MRI parameters against traditional pretreatment survival indicators. Materials and Methods: A retrospective study was undertaken. Approval had previously been granted for the retrospective use of such data, and the need for informed consent was waived. Prognostic value of pretreatment DCE-MRI parameters and clinical data was assessed via Cox proportional hazards models. The variables retained by the final overall survival Cox proportional hazards model were utilized to stratify risk of death within 5 years. Results: One hundred twelve subjects were entered into the analysis. Regarding disease-free survival-negative estrogen receptor status, T3 or higher clinical tumor stage, large ( > 9.8 cm 3 ) MR tumor volume, higher 95th percentile ( > 79%) percentage enhancement, and reduced ( > 0.22) circularity represented the retained model variables. Similar results were noted for the overall survival with negative estrogen receptor status, T3 or higher clinical tumor stage, and large ( > 9.8 cm 3 ) MR tumor volume, again all been retained by the model in addition to higher ( > 0.71) 25th percentile area under the enhancement curve. Accuracy of risk stratification based on either traditional (59%) or DCEMRI (65%) survival indicators performed to a similar level. However, combined traditional and MR risk stratification resulted in the highest accuracy (86%). Conclusions: Multivariate survival analysis has revealed thatmodel-retained DCEMRI variables provide independent prognostic information complementing traditional survival indicators and as such could help to appropriately stratify treatment

East Lancashire Research 2008

East Lancashire Research 200

Minkowski functionals: An MRI texture analysis tool for determination of the aggressiveness of breast cancer

Purpose: This work aims to see whether Minkowski Functionals can be used to distinguish between cancer types before chemotherapy treatment has begun, and whether a response to treatment can be predicted by an initial scan alone. Methods: Fat-nulled T1w 3T DCE-MRI scans were taken of 100 cases of biopsy confirmed breast cancer and a series of binary images created on lesion containing slices. Minkowski Functionals were calculated for each binary image and the change in these values as the binary threshold was raised was described using 6th order polynomials. These polynomials were used to compare between patient sub-groups, for triple negative breast cancer (TNBC) status, chemotherapy response, biopsy grade, nodal status, and lymphovascular invasion status. Results: When using Minkowski Functionals statistically significant (p<0.05) differences were found between TNBC status, biopsy grade, and lymphovascular invasion status sub-groups for all methodologies. The analysis performance did not appear to be affected by the number of threshold steps used. Most notably, very strong differences (p≤0.01) were found between TNBC and other intrinsic subtype patients. When analysed with a binary logistic regression model, an AUC value of 0.917 (0.846 – 0.987, 95% CI) for TNBC classification was found. Conclusion: The method of texture analysis presented here provides a novel way to characterise tumours, and demonstrates clear differences between cancer groups which are detectable before treatment begins, and can help with treatment planning as a valuable prognosis tool

Chelator free gallium-68 radiolabelling of silica coated iron oxide nanorods via surface interactions

The commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities. Herein we describe a new class of silica coated iron–oxide nanorods (NRs) coated with polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies of the coated NRs validate their composition and confirm their properties as in vivo T₂ MRI contrast agents. Radiolabelling studies with the positron emitting radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the silica coating, the macrocyclic chelator was not required for preparation of highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies show the expected high liver uptake of gallium-68 radiolabelled nanorods with no significant release of gallium-68 metal ions, validating our innovation to provide a novel simple method for labelling of iron oxide NRs with a radiometal in the absence of a chelating unit that can be used for high sensitivity liver imaging

The Slope of the Near Infrared Extinction Law

We determine the slope of the near infrared extinction power law (A$_{\lambda} \propto \lambda^{-\alpha}$) for 8 regions of the Galaxy between l$\sim27^{\circ}$ and $\sim100^{\circ}$. UKIDSS Galactic Plane Survey data are compared, in colour-colour space, with Galactic population synthesis model data reddened using a series of power laws and convolved through the UKIDSS filter profiles. Monte Carlo simulations allow us to determine the best fit value of $\alpha$ and evaluate the uncertainty. All values are consistent with each other giving an average extinction power law of $\alpha$=2.14$^{+0.04}_{-0.05}$. This is much steeper than most laws previously derived in the literature from colour excess ratios, which are typically between 1.6 and 1.8. We show that this discrepancy is due to an inappropriate choice of filter wavelength in conversion from colour excess ratios to $\alpha$ and that effective rather than isophotal wavelengths are more appropriate. In addition, curved reddening tracks, which depend on spectral type and filter system, should be used instead of straight vectors.Comment: Accepted by MNRAS: 11/08/09. 13 pages, 10 figures, 2 table

Registration of supine MR mammography with breast ultrasound for surgical planning of breast conserving surgery: a feasibility study

Purpose To report the feasibility, accuracy and initial clinical experience of the use of real-time magnetic resonance navigated ultrasound (rtMRnUS) in the surgical planning of breast-conserving surgery (BCS) via guide wire insertion. Materials and Methods 29 participants were recruited into this prospective ethics committee approved study. The first 4 cases were utilized as a training set. Participants underwent a supine contrast-enhanced breast MR examination with external fiducials and corresponding ink marks placed on the skin of the affected breast to act as co-registration pairs. MR examinations included both functional and morphological images. A LOGIQ E9 ultrasound system (GE Healthcare, Milwaukee, WI, USA) equipped with a 6 - 15 MHz transducer was utilized for rtMRnUS. To facilitate point co-registration of the previously acquired MR dataset with the real-time ultrasound, co-registration pairs were identified on both imaging modalities. The following co-registration quality metrics were recorded: root mean square deviation (RMSD), lesion and global accuracies. Post co-registration guide wire insertion was performed. Results Co-registration was successfully undertaken in all participants. Results from 25 participants are presented. The median (min, max) RMSD was 3.3 mm (0.6 mm, 8.8 mm). The global accuracy was assessed as very good (8), good (12), moderate (3) and poor (2) while the median (min, max) lesion accuracy was recorded at 8.9 mm (2.1 mm, 33.2 mm). Conclusion The use of rtMRnUS to facilitate guide wire insertion is a feasible technique. Generally, very good or good global registration can be expected. Lesion accuracy results indicate that a median difference, in 3 D space, of 9 mm can be expected between imaging modalities

A Concept for an STJ-based Spectrograph

We describe a multi-order spectrograph concept suitable for 8m-class telescopes, using the intrinsic spectral resolution of Superconducting Tunneling Junction detectors to sort the spectral orders. The spectrograph works at low orders, 1-5 or 1-6, and provides spectral coverage with a resolving power of R~8000 from the atmospheric cutoff at 320 nm to the long wavelength end of the infrared H or K band at 1800 nm or 2400 nm. We calculate that the spectrograph would provide substantial throughput and wavelength coverage, together with high time resolution and sufficient dynamic range. The concept uses currently available technology, or technologies with short development horizons, restricting the spatial sampling to two linear arrays; however an upgrade path to provide more spatial sampling is identified. All of the other challenging aspects of the concept - the cryogenics, thermal baffling and magnetic field biasing - are identified as being feasible.Comment: Accepted in Monthly Notices of the Royal Astronomical Society, 12 pages with 10 figure

Forces between clustered stereocilia minimize friction in the ear on a subnanometre scale

The detection of sound begins when energy derived from acoustic stimuli deflects the hair bundles atop hair cells. As hair bundles move, the viscous friction between stereocilia and the surrounding liquid poses a fundamental challenge to the ear's high sensitivity and sharp frequency selectivity. Part of the solution to this problem lies in the active process that uses energy for frequency-selective sound amplification. Here we demonstrate that a complementary part involves the fluid-structure interaction between the liquid within the hair bundle and the stereocilia. Using force measurement on a dynamically scaled model, finite-element analysis, analytical estimation of hydrodynamic forces, stochastic simulation and high-resolution interferometric measurement of hair bundles, we characterize the origin and magnitude of the forces between individual stereocilia during small hair-bundle deflections. We find that the close apposition of stereocilia effectively immobilizes the liquid between them, which reduces the drag and suppresses the relative squeezing but not the sliding mode of stereociliary motion. The obliquely oriented tip links couple the mechanotransduction channels to this least dissipative coherent mode, whereas the elastic horizontal top connectors stabilize the structure, further reducing the drag. As measured from the distortion products associated with channel gating at physiological stimulation amplitudes of tens of nanometres, the balance of forces in a hair bundle permits a relative mode of motion between adjacent stereocilia that encompasses only a fraction of a nanometre. A combination of high-resolution experiments and detailed numerical modelling of fluid-structure interactions reveals the physical principles behind the basic structural features of hair bundles and shows quantitatively how these organelles are adapted to the needs of sensitive mechanotransduction.Comment: 21 pages, including 3 figures. For supplementary information, please see the online version of the article at http://www.nature.com/natur

Rethinking the British World

Copyright @ 2013 The North American Conference on British StudiesThis article rethinks the concept of the “British World” by paying close attention to the voices of those who attended the 1903 Allied Colonial Universities Conference. They identified not one, but three different kinds of British world space. Mapped, respectively, by ideas and emotions, by networks and exchange, and by the specific sites of empire, this article suggests that, in the light of criticisms the British World concept has faced, and in the context of recent scholarship on the social and material production of space, this tripartite approach might offer a useful framework for British and imperial historians interested in the history of the global

A Recombinant Respiratory Syncytial Virus Vaccine Candidate Attenuated by a Low-Fusion F Protein Is Immunogenic and Protective against Challenge in Cotton Rats

ABSTRACT Although respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants, a safe and effective vaccine is not yet available. Live-attenuated vaccines (LAVs) are the most advanced vaccine candidates in RSV-naive infants. However, designing an LAV with appropriate attenuation yet sufficient immunogenicity has proven challenging. In this study, we implemented reverse genetics to address these obstacles with a multifaceted LAV design that combined the codon deoptimization of genes for nonstructural proteins NS1 and NS2 (dNS), deletion of the small hydrophobic protein (ΔSH) gene, and replacement of the wild-type fusion (F) protein gene with a low-fusion RSV subgroup B F consensus sequence of the Buenos Aires clade (BAF). This vaccine candidate, RSV-A2-dNS-ΔSH-BAF (DB1), was attenuated in two models of primary human airway epithelial cells and in the upper and lower airways of cotton rats. DB1 was also highly immunogenic in cotton rats and elicited broadly neutralizing antibodies against a diverse panel of recombinant RSV strains. When vaccinated cotton rats were challenged with wild-type RSV A, DB1 reduced viral titers in the upper and lower airways by 3.8 log 10 total PFU and 2.7 log 10 PFU/g of tissue, respectively, compared to those in unvaccinated animals ( P < 0.0001). DB1 was thus attenuated, highly immunogenic, and protective against RSV challenge in cotton rats. DB1 is the first RSV LAV to incorporate a low-fusion F protein as a strategy to attenuate viral replication and preserve immunogenicity. IMPORTANCE RSV is a leading cause of infant hospitalizations and deaths. The development of an effective vaccine for this high-risk population is therefore a public health priority. Although live-attenuated vaccines have been safely administered to RSV-naive infants, strategies to balance vaccine attenuation with immunogenicity have been elusive. In this study, we introduced a novel strategy to attenuate a recombinant RSV vaccine by incorporating a low-fusion, subgroup B F protein in the genetic background of codon-deoptimized nonstructural protein genes and a deleted small hydrophobic protein gene. The resultant vaccine candidate, DB1, was attenuated, highly immunogenic, and protective against RSV challenge in cotton rats