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

Meeting the design challenges of nano-CMOS electronics: an introduction to an upcoming EPSRC pilot project

The years of ‘happy scaling’ are over and the fundamental challenges that the semiconductor industry faces, at both technology and device level, will impinge deeply upon the design of future integrated circuits and systems. This paper provides an introduction to these challenges and gives an overview of the Grid infrastructure that will be developed as part of a recently funded EPSRC pilot project to address them, and we hope, which will revolutionise the electronics design industry

Evolutionary history and identification of conservation units in the giant otter, Pteronura brasiliensis.

The giant otter, Pteronura brasiliensis, occupies a range including the major drainage basins of South America, yet the degree of structure that exists within and among populations inhabiting these drainages is unknown. We sequenced portions of the mitochondrial DNA (mtDNA) cytochrome b (612 bp) and control region (383 bp) genes in order to determine patterns of genetic variation within the species. We found high levels of mtDNA haplotype diversity (h = 0.93 overall) and support for subdivision into four distinct groups of populations, representing important centers of genetic diversity and useful units for prioritizing conservation within the giant otter. We tested these results against the predictions of three hypotheses of Amazonian diversification (Pleistocene Refugia, Paleogeography, and Hydrogeology). While the phylogeographic pattern conformed to the predictions of the Refugia Hypothesis, molecular dating using a relaxed clock revealed the phylogroups diverged from one another between 1.69 and 0.84 Ma, ruling out the influence of Late Pleistocene glacial refugia. However, the role of Plio-Pleistocene climate change could not be rejected. While the molecular dating also makes the influence of geological arches according to the Paleogeography Hypothesis extremely unlikely, the recent Pliocene formation of the Fitzcarrald Arch and its effect of subsequently altering drainage pattern could not be rejected. The data presented here support the interactions of both climatic and hydrological changes resulting from geological activity in the Plio-Pleistocene, in shaping the phylogeographic structure of the giant otter

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

Measles vaccination and antibody response in autism spectrum disorder

OBJECTIVE: To test the hypothesis that measles vaccination was involved in the pathogenesis of autism spectrum disorders (ASD) as evidenced by signs of a persistent measles infection or abnormally persistent immune response shown by circulating measles virus or raised antibody titres in children with ASD who had been vaccinated against measles, mumps and rubella (MMR) compared with controls. DESIGN: Case-control study, community based. METHODS: A community sample of vaccinated children aged 10-12 years in the UK with ASD (n = 98) and two control groups of similar age, one with special educational needs but no ASD (n = 52) and one typically developing group (n = 90), were tested for measles virus and antibody response to measles in the serum. RESULTS: No difference was found between cases and controls for measles antibody response. There was no dose-response relationship between autism symptoms and antibody concentrations. Measles virus nucleic acid was amplified by reverse transcriptase-PCR in peripheral blood mononuclear cells from one patient with autism and two typically developing children. There was no evidence of a differential response to measles virus or the measles component of the MMR in children with ASD, with or without regression, and controls who had either one or two doses of MMR. Only one child from the control group had clinical symptoms of possible enterocolitis. CONCLUSION: No association between measles vaccination and ASD was shown

Mental Time Travel and Retirement Savings

We portray the valuation of retirement savings in terms of a mental time travel journey in which a proposed contribution to a pension plan is projected forward to the plan member’s retirement date and this projected value is then discounted back to today, thereby giving a present or personal value. We set this within a broader framework of pension planning, which seeks to smooth consumption over the lifecycle. We explain how two psychological biases—exponential growth bias and present bias—can lead to a difference between the initial value of a pension contribution and its present value, such a difference reflecting an asymmetry between projection and discounting, and how such a difference might lead to inadequate retirement savings and hence to a lower than desired standard of living in retirement. We consider how the two biases might be mitigated

Hollow-fiber membrane technology: Characterization and proposed use as a potential mimic of skin vascularization towards the development of a novel skin absorption in vitro model

Dermal bioavailability is currently estimated through skin penetration studies using ex vivo models, which lack any measure of capillary bed function, and thus do not fully reproduce physiological conditions. We propose a novel strategy to mimic skin vascularization using newly fabricated hollow fibers made from a biocompatible membrane material, polystyrene, which is hydrophobic if left untreated, or hydrophilic when its surface polarity is modified through plasma-treatment. Caffeine has been well studied in skin penetration assays and was used here to determine the permeation properties of the hollow fibers in a novel jacketed glass bioreactor. For hydrophobic fibers, approximately 87.2 % of the caffeine dose did not penetrate the porous surface; 0.2 % of the dose was collected after 24 h (permeated through the pores), and therefore 12.6 % of the initial dose was suspected to block the membrane. For hydrophilic fibers, both the percentage of the initial dose that permeated and that of blocking caffeine increased to 1.2 % and 35.2 % respectively. It was concluded that caffeine permeated the hollow fibers at similar times of clearance to those observed in vivo, and therefore shows that this new model could provide a surrogate for capillary-based clearance in in vitro skin absorption studies