Characterization of the Noise in Secondary Ion Mass Spectrometry Depth Profiles

The noise in the depth profiles of secondary ion mass spectrometry (SIMS) is studied using different samples under various experimental conditions. Despite the noise contributions from various parts of the dynamic SIMS process, its overall character agrees very well with the Poissonian rather than the Gaussian distribution in all circumstances. The Poissonian relation between the measured mean-square error (MSE) and mean can be used to describe our data in the range of four orders. The departure from this relation at high counts is analyzed and found to be due to the saturation of the channeltron used. Once saturated, the detector was found to exhibit hysteresis between rising and falling input flux and output counts.Comment: 14 pages, 4 postscript figures, to appear on J. Appl. Phy

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

Deficits in plasma oestradiol measurement in studies and management of breast cancer

The determination of plasma oestradiol has numerous applications in epidemiology, reproductive medicine and breast cancer management. Commercially available analytical methods, which measure the hormone levels without prior purification, have been successfully developed for measuring oestradiol in premenopausal women. The application of these methodologies to the quantification of the very low levels of oestradiol in postmenopausal women is more problematic in terms of accuracy and interpretation. The importance of using appropriate methodology is discussed and illustrated with data demonstrating the disparity in the results obtained when low levels of oestradiol were quantified using direct and indirect methods

Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): an open-label, multicentre, parallel-group, randomised, phase 3 trial

BACKGROUND:Preoperative and perioperative aromatase inhibitor (POAI) therapy has the potential to improve outcomes in women with operable oestrogen receptor-positive primary breast cancer. It has also been suggested that tumour Ki67 values after 2 weeks (Ki67_{2W}) of POAI predicts individual patient outcome better than baseline Ki67 (Ki67_{B}). The POETIC trial aimed to test these two hypotheses. METHODS: POETIC was an open-label, multicentre, parallel-group, randomised, phase 3 trial (done in 130 UK hospitals) in which postmenopausal women aged at least 50 years with WHO performance status 0–1 and hormone receptor-positive, operable breast cancer were randomly assigned (2:1) to POAI (letrozole 2·5 mg per day orally or anastrozole 1 mg per day orally) for 14 days before and following surgery or no POAI (control). Adjuvant treatment was given as per UK standard local practice. Randomisation was done centrally by computer-generated permuted block method (variable block size of six or nine) and was stratified by hospital. Treatment allocation was not masked. The primary endpoint was time to recurrence. A key second objective explored association between Ki67 (dichotomised at 10%) and disease outcomes. The primary analysis for clinical endpoints was by modified intention to treat (excluding patients who withdrew consent). For Ki67 biomarker association and endpoint analysis, the evaluable population included all randomly assigned patients who had paired Ki67 values available. This study is registered with ClinicalTrials.gov, NCT02338310; the European Clinical Trials database, EudraCT2007-003877-21; and the ISRCTN registry, ISRCTN63882543. Recruitment is complete and long-term follow-up is ongoing. FINDINGS: Between Oct 13, 2008, and April 16, 2014, 4480 women were recruited and randomly assigned to POAI (n=2976) or control (n=1504). On Feb 6, 2018, median follow-up was 62·9 months (IQR 58·1–74·1). 434 (10%) of 4480 women had a breast cancer recurrence (280 [9%] POAI; 154 [10%] control), hazard ratio 0·92 (95% CI 0·75–1·12); p=0·40 with the proportion free from breast cancer recurrence at 5 years of 91·0% (95% CI 89·9–92·0) for patients in the POAI group and 90·4% (88·7–91·9) in the control group. Within the POAI-treated HER2-negative subpopulation, 5-year recurrence risk in women with low Ki67B and Ki672W (low–low) was 4·3% (95% CI 2·9–6·3), 8·4% (6·8–10·5) with high Ki67B and low Ki672W (high–low) and 21·5% (17·1–27·0) with high Ki67B and Ki672W (high–high). Within the POAI-treated HER2-positive subpopulation, 5-year recurrence risk in the low–low group was 10·1% (95% CI 3·2–31·3), 7·7% (3·4–17·5) in the high–low group, and 15·7% (10·1–24·4) in the high–high group. The most commonly reported grade 3 adverse events were hot flushes (20 [1%] of 2801 patients in the POAI group vs six [<1%] of 1400 in the control group) and musculoskeletal pain (29 [1%] vs 13 [1%]). No treatment-related deaths were reported. INTERPRETATION: POAI has not been shown to improve treatment outcome, but can be used without detriment to help select appropriate adjuvant therapy based on tumour Ki67. Most patients with low Ki67_{B} or low POAI-induced Ki67_{2W} do well with adjuvant standard endocrine therapy (giving consideration to clinical–pathological factors), whereas those whose POAI-induced Ki67_{2W} remains high might benefit from further adjuvant treatment or trials of new therapies