The Hierarchical Formation of the Galactic Disk

I review the results of recent cosmological simulations of galaxy formation that highlight the importance of satellite accretion in the formation of galactic disks. Tidal debris of disrupted satellites may contribute to the disk component if they are compact enough to survive the decay and circularization of the orbit as dynamical friction brings the satellite into the disk plane. This process may add a small but non-negligible fraction of stars to the thin and thick disks, and reconcile the presence of very old stars with the protracted merging history expected in a hierarchically clustering universe. I discuss various lines of evidence which suggest that this process may have been important during the formation of the Galactic disk.Comment: paper to be read at the "Penetrating Bars through Masks of Cosmic Dust" conference in South Afric

Oscillations of aqueous PEDOT:PSS fluid droplets and the properties of complex fluids in drop-on-demand inkjet printing

Shear-thinning aqueous poly(3,4-ethylenedioxythiophene): poly(styrene sulphonate) (PEDOT:PSS) fluids were studied under the conditions of drop-on-demand inkjet printing. Ligament retraction caused oscillation of the resulting drops, from which values of surface tension and viscosity were derived. Effective viscosities of <4 mPa s at drop oscillation frequencies of 13–33 kHz were consistent with conventional high-frequency rheometry, with only a small possible contribution from viscoelasticity with a relaxation time of about 6 μs. Strong evidence was found that the viscosity, reduced by shear-thinning in the printhead nozzle, recovered as the drop formed. The low viscosity values measured for the drops in flight were associated with the strong oscillation induced by ligament retraction, while for a weakly perturbed drop the viscosity remained high. Surface tension values in the presence of surfactant were significantly higher than the equilibrium values, and consistent with the surface age of the drops. [Graphical abstract - see article]This work was supported by EPSRC and a consortium of industrial partners (EPSRC Grant no. EP/H018913/1: Innovation in industrial inkjet technology). The high-speed camera and high power flash lamp were provided by the EPSRC Engineering Instrument Pool and we thank Adrian Walker for his help.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.jnnfm.2015.05.00

Mammographic density, lobular involution, and risk of breast cancer

In this review, we propose that age-related changes in mammographic density and breast tissue involution are closely related phenomena, and consider their potential relevance to the aetiology of breast cancer. We propose that the reduction in mammographic density that occurs with increasing age, parity and menopause reflects the involution of breast tissue. We further propose that age-related changes in both mammographic density and breast tissue composition are observable and measurable phenomena that resemble Pike's theoretical construct of ‘breast tissue ageing'. Extensive mammographic density and delayed breast involution are both associated with an increased risk of breast cancer and are consistent with the hypothesis of the Pike model that cumulative exposure of breast tissue to hormones and growth factors that stimulate cell division, as well as the accumulation of genetic damage in breast cells, are major determinants of breast cancer incidence

Incidence and drug treatment of emotional distress after cancer diagnosis : a matched primary care case-control study

Notes This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License.Peer reviewedPublisher PD

Genetic variation in the estrogen metabolic pathway and mammographic density as an intermediate phenotype of breast cancer

Introduction: Several studies have examined the effect of genetic variants in genes involved in the estrogen metabolic pathway on mammographic density, but the number of loci studied and the sample sizes evaluated have been small and pathways have not been evaluated comprehensively. In this study, we evaluate the association between mammographic density and genetic variants of the estrogen metabolic pathway. Methods: A total of 239 SNPs in 34 estrogen metabolic genes were studied in 1,731 Swedish women who participated in a breast cancer case-control study, of which 891 were cases and 840 were controls. Film mammograms of the medio-lateral oblique view were digitalized and the software Cumulus was used for computer-assisted semi-automated thresholding of mammographic density. Generalized linear models controlling for possible confounders were used to evaluate the effects of SNPs on mammographic density. Results found to be nominally significant were examined in two independent populations. The admixture maximum likelihood-based global test was performed to evaluate the cumulative effect from multiple SNPs within the whole metabolic pathway and three subpathways for androgen synthesis, androgen-to-estrogen conversion and estrogen removal. Results: Genetic variants of genes involved in estrogen metabolism exhibited no appreciable effect on mammographic density. None of the nominally significant findings were validated. In addition, global analyses on the overall estrogen metabolic pathway and its subpathways did not yield statistically significant results. Conclusions: Overall, there is no conclusive evidence that genetic variants in genes involved in the estrogen metabolic pathway are associated with mammographic density in postmenopausal women

A Dynamic Knowledge Management Framework for the High Value Manufacturing Industry

Dynamic Knowledge Management (KM) is a combination of cultural and technological factors, including the cultural factors of people and their motivations, technological factors of content and infrastructure and, where these both come together, interface factors. In this paper a Dynamic KM framework is described in the context of employees being motivated to create profit for their company through product development in high value manufacturing. It is reported how the framework was discussed during a meeting of the collaborating company’s (BAE Systems) project stakeholders. Participants agreed the framework would have most benefit at the start of the product lifecycle before key decisions were made. The framework has been designed to support organisational learning and to reward employees that improve the position of the company in the market place

A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease

BACKGROUND: Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings. METHODS: Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC -ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration. RESULTS: A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6-73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions. CONCLUSIONS: These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy. TRIAL REGISTRATION: ISRCTN Registry 48776874

Grassmannian flows and applications to nonlinear partial differential equations

We show how solutions to a large class of partial differential equations with nonlocal Riccati-type nonlinearities can be generated from the corresponding linearized equations, from arbitrary initial data. It is well known that evolutionary matrix Riccati equations can be generated by projecting linear evolutionary flows on a Stiefel manifold onto a coordinate chart of the underlying Grassmann manifold. Our method relies on extending this idea to the infinite dimensional case. The key is an integral equation analogous to the Marchenko equation in integrable systems, that represents the coodinate chart map. We show explicitly how to generate such solutions to scalar partial differential equations of arbitrary order with nonlocal quadratic nonlinearities using our approach. We provide numerical simulations that demonstrate the generation of solutions to Fisher--Kolmogorov--Petrovskii--Piskunov equations with nonlocal nonlinearities. We also indicate how the method might extend to more general classes of nonlinear partial differential systems.Comment: 26 pages, 2 figure

The spatial distribution of radiodense breast tissue: a longitudinal study

Introduction Mammographic breast density is one of the strongest known markers of susceptibility to breast cancer. To date research into density has relied on a single measure ( for example, percent density (PD)) summarising the average level of density for the whole breast, with no consideration of how the radiodense tissue may be distributed. This study aims to investigate the spatial distribution of density within the breast using 493 mammographic images from a sample of 165 premenopausal women (similar to 3 medio-lateral oblique views per woman).Methods Each breast image was divided into 48 regions and the PD for the whole breast ( overall PD) and for each one of its regions ( regional PD) was estimated. The spatial autocorrelation ( Moran's I value) of regional PD for each image was calculated to investigate spatial clustering of density, whether the degree of clustering varied between a woman's two breasts and whether it was affected by age and other known density correlates.Results The median Moran's / value for 165 women was 0.31 (interquartile range: 0.26, 0.37), indicating a clustered pattern. High-density areas tended to cluster in the central regions of the breast, regardless of the level of overall PD, but with considerable between-woman variability in regional PD. The degree of clustering was similar between a woman's two breasts (mean within-woman difference in Moran's / values between left and right breasts = 0.00 (95% confidence interval (CI) = -0.01, 0.01); P = 0.76) and did not change with aging (mean within-woman difference in I values between screens taken on average 8 years apart = 0.01 (95% CI = -0.01, 0.02); P = 0.30). Neither parity nor age at first birth affected the level of spatial autocorrelation of density, but increasing body mass index (BMI) was associated with a decrease in the degree of spatial clustering.Conclusions This study is the first to demonstrate that the distribution of radiodense tissue within the breast is spatially autocorrelated, generally with the high-density areas clustering in the central regions of the breast. The degree of clustering was similar within a woman's two breasts and between women, and was little affected by age or reproductive factors although it declined with increasing BMI