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

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

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

Image Registration for Quantitative Parametric Response Mapping of Cancer Treatment Response

AbstractImaging biomarkers capable of early quantification of tumor response to therapy would provide an opportunity to individualize patient care. Image registration of longitudinal scans provides a method of detecting treatment-associated changes within heterogeneous tumors by monitoring alterations in the quantitative value of individual voxels over time, which is unattainable by traditional volumetric-based histogram methods. The concepts involved in the use of image registration for tracking and quantifying breast cancer treatment response using parametric response mapping (PRM), a voxel-based analysis of diffusion-weighted magnetic resonance imaging (DW-MRI) scans, are presented. Application of PRM to breast tumor response detection is described, wherein robust registration solutions for tracking small changes in water diffusivity in breast tumors during therapy are required. Methodologies that employ simulations are presented for measuring expected statistical accuracy of PRM for response assessment. Test-retest clinical scans are used to yield estimates of system noise to indicate significant changes in voxel-based changes in water diffusivity. Overall, registration-based PRM image analysis provides significant opportunities for voxel-based image analysis to provide the required accuracy for early assessment of response to treatment in breast cancer patients receiving neoadjuvant chemotherapy

'Everyday memory' impairments in autism spectrum disorders

‘Everyday memory’ is conceptualised as memory within the context of day-to-day life and, despite its functional relevance, has been little studied in individuals with autism spectrum disorders (ASDs). In the first study of its kind, 94 adolescents with an ASD and 55 without an ASD completed measures of everyday memory from the Rivermead Behavioural Memory Test (RBMT) and a standard word recall task (Children’s Auditory Verbal Learning Test-2: CAVLT-2). The ASD group showed significant impairments on the RBMT, including in prospective memory, alongside impaired performance on the CAVLT-2. Social and communication ability was significantly associated with prospective remembering in an everyday memory context but not with the CAVLT-2. The complex nature of everyday memory and its relevance to ASD is discussed

The Unseen Population of F to K-type Companions to Hot Subdwarf Stars

We present a method to select hot subdwarf stars with A to M-type companions using photometric selection criteria. We cover a wide range in wavelength by combining GALEX ultraviolet data, optical photometry from the SDSS and the Carlsberg Meridian telescope, near-infrared data from 2MASS and UKIDSS. We construct two complimentary samples, one by matching GALEX, CMC and 2MASS, as well as a smaller, but deeper, sample using GALEX, SDSS and UKIDSS. In both cases, a large number of composite subdwarf plus main-sequence star candidates were found. We fit their spectral energy distributions with a composite model in order to estimate the subdwarf and companion star effective temperatures along with the distance to each system. The distribution of subdwarf effective temperature was found to primarily lie in the 20,000 - 30,000 K regime, but we also find cooler subdwarf candidates, making up ~5-10 per cent. The most prevalent companion spectral types were seen to be main-sequence stars between F0 and K0, while subdwarfs with M-type companions appear much rarer. This is clear observational confirmation that a very efficient first stable Roche-lobe overflow channel appears to produce a large number of subdwarfs with F to K-type companions. Our samples thus support the importance of binary evolution for subdwarf formation.Comment: 30 pages, 10 figures, 11 tables. Accepted for publication in MNRA

Public health professionals' perceptions toward provision of health protection in England: a survey of expectations of Primary Care Trusts and Health Protection Units in the delivery of health protection

BACKGROUND: Effective health protection requires systematised responses with clear accountabilities. In England, Primary Care Trusts and the Health Protection Agency both have statutory responsibilities for health protection. A Memorandum of Understanding identifies responsibilities of both parties, but there is a potential lack of clarity about responsibility for specific health protection functions. We aimed to investigate professionals' perceptions of responsibility for different health protection functions, to inform future guidance for, and organisation of, health protection in England. METHODS: We sent a postal questionnaire to all health protection professionals in England from the following groups: (a) Directors of Public Health in Primary Care Trusts; (b) Directors of Health Protection Units within the Health Protection Agency; (c) Directors of Public Health in Strategic Health Authorities and; (d) Regional Directors of the Health Protection Agency RESULTS: The response rate exceeded 70%. Variations in perceptions of who should be, and who is, delivering health protection functions were observed within, and between, the professional groups (a)-(d). Concordance in views of which organisation should, and which does deliver was high (≥90%) for 6 of 18 health protection functions, but much lower (≤80%) for 6 other functions, including managing the implications of a case of meningitis out of hours, of landfill environmental contamination, vaccination in response to mumps outbreaks, nursing home infection control, monitoring sexually transmitted infections and immunisation training for primary care staff. The proportion of respondents reporting that they felt confident most or all of the time in the safe delivery of a health protection function was strongly correlated with the concordance (r = 0.65, P = 0.0038). CONCLUSION: Whilst we studied professionals' perceptions, rather than actual responses to incidents, our study suggests that there are important areas of health protection where consistent understanding of responsibility for delivery is lacking. There are opportunities to clarify the responsibility for health protection in England, perhaps learning from the approaches used for those health protection functions where we found consistent perceptions of accountability

Comparison of microbiological diagnosis of urinary tract infection in young children by routine health service laboratories and a research laboratory: Diagnostic cohort study

OBJECTIVES: To compare the validity of diagnosis of urinary tract infection (UTI) through urine culture between samples processed in routine health service laboratories and those processed in a research laboratory. POPULATION AND METHODS: We conducted a prospective diagnostic cohort study in 4808 acutely ill children aged <5 years attending UK primary health care. UTI, defined as pure/predominant growth ≥105 CFU/mL of a uropathogen (the reference standard), was diagnosed at routine health service laboratories and a central research laboratory by culture of urine samples. We calculated areas under the receiver-operator curve (AUC) for UTI predicted by pre-specified symptoms, signs and dipstick test results (the "index test"), separately according to whether samples were obtained by clean catch or nappy (diaper) pads. RESULTS: 251 (5.2%) and 88 (1.8%) children were classified as UTI positive by health service and research laboratories respectively. Agreement between laboratories was moderate (kappa = 0.36; 95% confidence interval [CI] 0.29, 0.43), and better for clean catch (0.54; 0.45, 0.63) than nappy pad samples (0.20; 0.12, 0.28). In clean catch samples, the AUC was lower for health service laboratories (AUC = 0.75; 95% CI 0.69, 0.80) than the research laboratory (0.86; 0.79, 0.92). Values of AUC were lower in nappy pad samples (0.65 [0.61, 0.70] and 0.79 [0.70, 0.88] for health service and research laboratory positivity, respectively) than clean catch samples. CONCLUSIONS: The agreement of microbiological diagnosis of UTI comparing routine health service laboratories with a research laboratory was moderate for clean catch samples and poor for nappy pad samples and reliability is lower for nappy pad than for clean catch samples. Positive results from the research laboratory appear more likely to reflect real UTIs than those from routine health service laboratories, many of which (particularly from nappy pad samples) could be due to contamination. Health service laboratories should consider adopting procedures used in the research laboratory for paediatric urine samples. Primary care clinicians should try to obtain clean catch samples, even in very young children