Ion yields and erosion rates for Si1−xGex(0x1) ultralow energy O2+ secondary ion mass spectrometry in the energy range of 0.25–1 keV

We report the SIMS parameters required for the quantitative analysis of Si1−xGex across the range of 0 ≤ x ≤ 1 when using low energy O2+ primary ions at normal incidence. These include the silicon and germanium secondary ion yield [i.e., the measured ion signal (ions/s)] and erosion rate [i.e., the speed at which the material sputters (nm/min)] as a function of x. We show that the ratio Rx of erosion rates, Si1−xGex/Si, at a given x is almost independent of beam energy, implying that the properties of the altered layer are dominated by the interaction of oxygen with silicon. Rx shows an exponential dependence on x. Unsurprisingly, the silicon and germanium secondary ion yields are found to depart somewhat from proportionality to (1−x) and x, respectively, although an approximate linear relationship could be used for quantification across around 30% of the range of x (i.e., a reference material containing Ge fraction x would give reasonably accurate quantification across the range of ±0.15x). Direct comparison of the useful (ion) yields [i.e., the ratio of ion yield to the total number of atoms sputtered for a particular species (ions/atom)] and the sputter yields [i.e., the total number of atoms sputtered per incident primary ion (atoms/ions)] reveals a moderate matrix effect where the former decrease monotonically with increasing x except at the lowest beam energy investigated (250 eV). Here, the useful yield of Ge is found to be invariant with x. At 250 eV, the germanium ion and sputter yields are proportional to x for all x

Dopant Spatial Distributions: Sample Independent Response Function And Maximum Entropy Reconstruction

We demonstrate the use of maximum entropy based deconvolution to reconstruct boron spatial distribution from the secondary ion mass spectrometry (SIMS) depth profiles on a system of variously spaced boron $\delta$-layers grown in silicon. Sample independent response functions are obtained using a new method which reduces the danger of incorporating real sample behaviour in the response. Although the original profiles of different primary ion energies appear quite differently, the reconstructed distributions agree well with each other. The depth resolution in the reconstructed data is increased significantly and segregation of boron at the near surface side of the $\delta$-layers is clearly shown.Comment: 5 two-columne pages, 3 postscript figures, to appear in Phys. Rev. B1

Updated recommendations for HER2 testing in the UK

This paper serves to update previously published guidance on rationale and methodology for HER2 laboratory testing following the recommendation for the use of HER2 targeted treatment in the management of advanced breast cancer in the UK. Emphasis is placed on the standardisation of methodology and assessment and strategies to achieve high quality performance. A two phase testing algorithm based on first line immunocytochemistry evaluation and second line fluorescence in situ hybridisation assessment of borderline cases is recommended. To ensure maintenance of expertise, an annual caseload volume of at least 250 cases is recommended for laboratories providing a testing service

Tamoxifen may prevent both ER+ and ER- breast cancers and select for ER- carcinogenesis: an alternative hypothesis

INTRODUCTION: Breast Cancer Prevention Trial (BCPT) and Multiple Outcomes of Raloxifene (MORE) data have been interpreted to indicate that tamoxifen reduces the risk of ER+ but not ER- breast carcinogenesis. We explored whether these data also support an alternative hypothesis, that tamoxifen influences the natural history of both ER+ and ER- cancers, that it may be equally effective in abrogating or delaying ER- and ER+ carcinogenesis, and place selection pressure, in some cases, for the outgrowth of ER- cancers. METHODS: BCPT and MORE data were used to investigate whether: first, tamoxifen could reduce equally the emergence of ER- and ER+ tumors; and second, tamoxifen could select a fraction of emerging ER+ cancers and promote their transformation to ER- cancers. Assuming that some proportion, Z, of ER+ tumors becomes ER- after tamoxifen exposure and that the risk reduction for both ER- and ER+ tumors is equal, we solved for both the transformation rate and the risk reduction rate. RESULTS: If tamoxifen equally reduces the incidence of ER+ and ER- tumors by 60%, the BCPT results are achieved with a transformation of approximately Z = 20% of ER+ to ER- tumors. Validation with MORE data using an equal risk reduction of 60% associated with tamoxifen produces an almost identical transformation rate Z of 23%. CONCLUSION: Data support an alternative hypothesis that tamoxifen may promote ER- carcinogenesis from a precursor lesion that would otherwise have developed as ER+ without tamoxifen selection

A brainstem to hypothalamic arcuate nucleus GABAergic circuit drives feeding

We gratefully acknowledge Dr F. Naneix for advice on optogenetics and editorial advice, and staff within the University of Aberdeen Medical Research Facility and the Microscopy Facility for their technical assistance. This work was supported by the ERC (MSCA-IF-NeuroEE538 660219) to PBM, Wellcome Trust Institutional Strategic Support Fund (204815/Z/16/Z) to PBM and LKH, and the Biotechnology and Biological Sciences Research Council (BB/V010557/1) to JAG and (BB/V016849/1) to LKH and SS. GKCD is funded by a BBSRC CASE 4-year PhD studentship, co-funded by Novo Nordisk. GSHY is funded by the UK Medical Research Council (MC_UU_00014/1).Publisher PD

Comparing computer-generated and pathologist-generated tumour segmentations for immunohistochemical scoring of breast tissue microarrays

BACKGROUND: Tissue microarrays (TMAs) have become a valuable resource for biomarker expression in translational research. Immunohistochemical (IHC) assessment of TMAs is the principal method for analysing large numbers of patient samples, but manual IHC assessment of TMAs remains a challenging and laborious task. With advances in image analysis, computer-generated analyses of TMAs have the potential to lessen the burden of expert pathologist review. METHODS: In current commercial software computerised oestrogen receptor (ER) scoring relies on tumour localisation in the form of hand-drawn annotations. In this study, tumour localisation for ER scoring was evaluated comparing computer-generated segmentation masks with those of two specialist breast pathologists. Automatically and manually obtained segmentation masks were used to obtain IHC scores for thirty-two ER-stained invasive breast cancer TMA samples using FDA-approved IHC scoring software. RESULTS: Although pixel-level comparisons showed lower agreement between automated and manual segmentation masks (κ=0.81) than between pathologists' masks (κ=0.91), this had little impact on computed IHC scores (Allred; [Image: see text]=0.91, Quickscore; [Image: see text]=0.92). CONCLUSIONS: The proposed automated system provides consistent measurements thus ensuring standardisation, and shows promise for increasing IHC analysis of nuclear staining in TMAs from large clinical trials

Comparison of EndoPredict and EPclin With Oncotype DX Recurrence Score for Prediction of Risk of Distant Recurrence After Endocrine Therapy

This work was supported by the Royal Marsden National Institutes of Health Biomedical Research Centre and the Breast Cancer Now grant awarded to MD (CTR-Q4-Y1) and the Cancer Research UK grant awarded to JC (C569/A16891)