An evaluation of the kinematic approximation in helium atom scattering using wavepacket calculations

We use 2-D wavepacket calculations to examine the scattering of helium atoms from dynamic assemblies of surface adsorbates, and in particular to explore the validity of the widely used kinematic scattering approximation. The wavepacket calculations give exact results for quasi-elastic scattering that are closely analogous to time-of-flight (TOF) experiments and they are analysed as such. A scattering potential is chosen to represent 8 meV helium atoms scattering from sodium atoms adsorbed on a Cu(001) surface and the adsorbates in the model move according to an independent Langevin equation. The energy broadening in the quasi-elastic scattering is obtained as a function of parallel momentum transfer and compared with the corresponding results using the kinematic scattering approximation. Under most circumstances the kinematic approximation and the more accurate wavepacket method are in good agreement; however, there are cases where the two methods give different results. We relate these differences to pathological features in the scattering form-factor.EPSRC Studentship, Royal Society University Research Fellowshi

Herd-level risk factors associated with Leptospira Hardjo seroprevalence in Beef/Suckler herds in the Republic of Ireland

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to investigate risk factors for herd seropositivity to <it>Leptospira </it>Hardjo in Irish suckler herds. Herds were considered eligible for the study if they were unvaccinated and contained ≥ 9 breeding animals of beef breed which were ≥ 12 months of age. The country was divided into six regions using county boundaries. Herd and individual animal prevalence data were available from the results of a concurrent seroprevalence study. Herds were classified as either "Free from Infection" or "Infected" based on a minimum expected 40% within-herd prevalence.</p> <p>Questionnaires were posted to 320 farmers chosen randomly from 6 regions, encompassing 25 counties, of the Republic of Ireland. The questionnaire was designed to obtain information about vaccination; reproductive disease; breeding herd details; the presence of recognized risk factors from previous studies; and husbandry on each farm. Data collected from 128 eligible herds were subjected to statistical analysis.</p> <p>Results</p> <p>Following the use of Pearson's Chi-Square Test, those variables associated with a herd being "infected" with a significance level of P < 0.2 were considered as candidates for multivariable logistic regression modelling. Breeding herd size was found to be a statistically significant risk factor after multivariable logistic regression. The odds of a herd being positive for leptospiral infection were 5.47 times higher (P = 0.032) in herds with 14 to 23 breeding animals compared with herds with ≤ 13 breeding animals, adjusting for Region, and 7.08 times higher (P = 0.033) in herds with 32.6 to 142 breeding animals.</p> <p>Conclusions</p> <p>Breeding herd size was identified as a significant risk factor for leptospiral infection in Irish suckler herds, which was similar to findings of previous studies of leptospirosis in dairy herds.</p

Breast cancer histologic grading using digital microscopy: concordance and outcome association

Aims: Virtual microscopy utilising digital whole slide imaging (WSI) is increasingly used in breast pathology. Histologic grade is one of the strongest prognostic factors in breast cancer (BC). This study aims at investigating the agreement between BC grading using traditional light microscopy (LM) and digital whole slide imaging (WSI) with consideration of reproducibility and impact on outcome prediction. Methods: A large (n=1675) well-characterised cohort of BC originally graded by LM was re-graded using WSI. Two separate virtual-based grading sessions (V1 and V2) were performed with a three months washout period. Outcome was assessed using breast cancer specific and distant metastasis free survival. Results: The concordance between LM grading and WSI was strong (LM/SWI Cramer’s V: V1=0.576, and V2=0.579). The agreement regarding grade components was as follows: Tubule formation=0.538, Pleomorphism=0.422 and Mitosis=0.514. Greatest discordance was observed between adjacent grades whereas high/low grade discordance was uncommon (1.5%). The intra-observer agreement for the two WSI sessions was substantial for grade (V1/V2 Cramer’s V=0.676; kappa=0.648) and grade components (Cramer’s V T=0.628, P=0.573 and M=0.580). Grading using both platforms showed strong association with outcome (All p-value <0.001). Although mitotic scores assessed using both platforms were strongly associated with outcome, WSI tends to underestimate mitotic counts. Conclusions: Virtual microscopy is a reliable and reproducible method for assessing BC histologic grade. Regardless of the observer or assessment platform, histologic grade is a significant predictor of outcome. Continuing advances in imaging technology could potentially provide improved performance of WSI BC grading and in particular mitotic count assessment

Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer

Background: ATR-Chk1 signalling network is critical for genomic stability. ATR-Chk1 may be deregulated in breast cancer and have prognostic, predictive and therapeutic significance. Patients and methods: We investigated ATR and phosphorylated CHK1Ser345 protein (pChk1) expression in 1712 breast cancers (Nottingham Tenovus series). ATR and Chk1 mRNA were evaluated in 1950 breast cancers (METABRIC cohort). Pre-clinically, biological consequences of ATR gene knockdown or ATR inhibition by small molecule inhibitor (VE-821) were investigated in MCF-7 and MDA-MB-231 breast cancer cell lines and in non-tumorigenic breast epithelial cells (MCF10A). Results: High ATR and high cytoplasmic pChk1 expression was significantly associated with higher tumour stage, higher mitotic index, pleomorphism and lymphovascular invasion. In univariate analysis, high ATR and high cytoplasmic pChk1 protein expression was associated with shorter breast cancer specific survival (BCSS). In multivariate analysis, high ATR remains an independent predictor of adverse outcome. At the mRNA level, high Chk1 remains associated with aggressive phenotypes including lymph node positivity, high grade, Her-2 overexpression, triple-negative phenotype and molecular classes associated with aggressive behaviour and shorter survival.. Pre-clinically, Chk1 phosphorylation at serine 345 following replication stress (induced by gemcitabine or hydroxyurea treatment) was impaired in ATR knockdown and in VE-821 treated breast cancer cells. Doxycycline inducible knockdown of ATR suppressed growth, which was restored when ATR was re-expressed. Similarly, VE-821 treatment resulted in a dose dependent suppression of cancer cell growth and survival (MCF7 and MDA-MB-231) but had no effect on non-tumorigenic breast epithelial cells (MCF10A). Conclusions: We provides evidence that ATR and Chk1 are promising biomarkers and rational drug target for personalized therapy in breast cancer

Light dark sectors through the Fermion portal

Abstract Pairs of Standard Model fermions form dimension-3 singlet operators that can couple to new dark sector states. This “fermion portal” is to be contrasted with the lower-dimensional Higgs, vector and neutrino singlet portals. We characterise its distinct phenomenology and place effective field theory bounds on this framework, focusing on the case of fermion portals to a pair of light dark sector fermions. We obtain current and projected limits on the dimension-6 effective operator scale from a variety of meson decay experiments, missing energy and long-lived particle searches at colliders, as well as astrophysical and cosmological bounds. The DarkEFT public code is made available for recasting these limits, which we illustrate with various examples including an integrated- out heavy dark photon.</jats:p