Reliability of tissue microarrays in detecting protein expression and gene amplification in breast cancer

Tissue microarrays allow high throughput molecular profiling of diagnostic or predictive markers in cancer specimens and rapid validation of novel potential candidates identified from genomic and proteomic analyses in a large number of tumor samples. To validate the use of tissue microarray technology for all the main biomarkers routinely used to decide breast cancer prognostication and postsurgical adjuvant therapy, we constructed a tissue microarray from 97 breast tumors, with a single 0.6 mm core per specimen. Inummostaining; of tissue microarray sections and conventional full sections of each tumor were performed using well-characterized prognostic markers (estrogen receptor ER, progesterone receptor PR and c-erbB2). The full section versus tissue microarray concordance for these stains was 97% for ER, 98% for PR, and 97% for c-erbB2, respectively, with a strong statistical association (kappa value more than 0.90). Fluorescence in situ hybridization analysis for HER-2/neu gene amplification from the single-core tissue microarray was technically successful in about 90% (87/97) of the cases, with a concordance of 95% compared with parallel analyses with the full sections. The correlation with other pathological parameters was not significantly different between full-section and array-based results. It is concluded that the constructed tissue microarray with a single core per specimen ensures full biological representativeness to identify the associations between biomarkers and clinicopathological parameters, with no significant associated sampling bias.

A Robust Curve-Fitting Procedure for the Analysis of Plasmid DNA Strand Break Data from Gel Electrophoresis

A robust method for fitting to the results of gel electrophoresis assays of damage to plasmid DNA caused by radiation is presented. This method makes use of nonlinear regression to fit analytically derived dose response curves to observations of the supercoiled, open circular and linear plasmid forms simultaneously, allowing for more accurate results than fitting to individual forms. Comparisons with a commonly used analysis method show that while there is a relatively small benefit between the methods for data sets with small errors, the parameters generated by this method remain much more closely distributed around the true value in the face of increasing measurement uncertainties. This allows for parameters to be specified with greater confidence, reflected in a reduction of errors on fitted parameters. On test data sets, fitted uncertainties were reduced by 30%, similar to the improvement that would be offered by moving from triplicate to fivefold repeats (assuming standard errors). This method has been implemented in a popular spreadsheet package and made available online to improve its accessibility. (C) 2011 by Radiation Research Society

Application of STOPP and START criteria: interrater reliability among pharmacists

BACKGROUND: Inappropriate prescribing is a well-documented problem in older people. The new screening tools, STOPP (Screening Tool of Older Peoples' Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment) have been formulated to identify potentially inappropriate medications (PIMs) and potential errors of omissions (PEOs) in older patients. Consistent, reliable application of STOPP and START is essential for the screening tools to be used effectively by pharmacists. OBJECTIVE: To determine the interrater reliability among a group of clinical pharmacists in applying the STOPP and START criteria to elderly patients' records. METHODS: Ten pharmacists (5 hospital pharmacists, 5 community pharmacists) were given 20 patient profiles containing details including the patients' age and sex, current medications, current diagnoses, relevant medical histories, biochemical data, and estimated glomerular filtration rate. Each pharmacist applied the STOPP and START criteria to each patient record. The PIMs and PEOs identified by each pharmacist were compared with those of 2 academic pharmacists who were highly familiar with the application of STOPP and START. An interrater reliability analysis using the k statistic (chance corrected measure of agreement) was performed to determine consistency between pharmacists. RESULTS: The median ? coefficients for hospital pharmacists and community pharmacists compared with the academic pharmacists for STOPP were 0.89 and 0.88, respectively, while those for START were 0.91 and 0.90, respectively. CONCLUSIONS: Interrater reliability of STOPP and START tools between pharmacists working in different sectors is good. Pharmacists working in both hospitals and in the community can use STOPP and START reliably during their everyday practice to identify PIMs and PEOs in older patients.

Kin discriminators in the eusocial sweat bee Lasioglossum malachurum: the reliability of cuticular and Dufour's gland odours

The ability to discriminate degrees of relatedness may be expected to evolve if it allows unreciprocated altruism to be preferentially directed towards kin (Hamilton in J Theor Biol 7:1-16, 1964). We explored the possibility of kin recognition in the primitively eusocial halictid bee Lasioglossum malachurum by investigating the reliability of worker odour cues that can be perceived by workers to act as indicators of either nest membership or kinship. Cuticular and Dufour's gland compounds varied significantly among colonies of L. malachurum, providing the potential for nestmate discrimination. A significant, though weak, negative correlation between chemical distance and genetic relatedness (r = -0.055, p

The Type IIb SN 2008ax: spectral and light curve evolution

We present spectroscopy and photometry of the He-rich supernova (SN) 2008ax. The early-time spectra show prominent P-Cygni H lines, which decrease with time and disappear completely about 2 months after the explosion. In the same period He I lines become the most prominent spectral features. SN 2008ax displays the ordinary spectral evolution of a Type IIb supernova. A stringent pre-discovery limit constrains the time of the shock breakout of SN 2008ax to within only a few hours. Its light curve, which peaks in the B band about 20 d after the explosion, strongly resembles that of other He-rich core-collapse supernovae. The observed evolution of SN 2008ax is consistent with the explosion of a young Wolf-Rayet (of WNL type) star, which had retained a thin, low-mass shell of its original H envelope. The overall characteristics of SN 2008ax are reminiscent of those of SN 1993J, except for a likely smaller H mass. This may account for the findings that the progenitor of SN 2008ax was a WNL star and not a K supergiant as in the case of SN 1993J, that a prominent early-time peak is missing in the light curve of SN 2008ax, and that H alpha is observed at higher velocities in SN 2008ax than in SN 1993J.

Classical novae from the POINT-AGAPE microlensing survey of M31 - I. The nova catalogue

The POINT-AGAPE (Pixel-lensing Observations with the Isaac Newton Telescope-Andromeda Galaxy Amplified Pixels Experiment) survey is an optical search for gravitational microlensing events towards the Andromeda galaxy (M31). As well as microlensing, the survey is sensitive to many different classes of variable stars and transients. Here we describe the automated detection and selection pipeline used to identify M31 classical novae (CNe) and we present the resulting catalogue of 20 CN candidates observed over three seasons. CNe are observed both in the bulge region as well as over a wide area of the M31 disc. Nine of the CNe are caught during the final rise phase and all are well sampled in at least two colours. The excellent light-curve coverage has allowed us to detect and classify CNe over a wide range of speed class, from very fast to very slow. Among the light curves is a moderately fast CN exhibiting entry into a deep transition minimum, followed by its final decline. We have also observed in detail a very slow CN which faded by only 0.01 mag d(-1) over a 150-d period. We detect other interesting variable objects, including one of the longest period and most luminous Mira variables. The CN catalogue constitutes a uniquely well-sampled and objectively-selected data set with which to study the statistical properties of CNe in M31, such as the global nova rate, the reliability of novae as standard-candle distance indicators and the dependence of the nova population on stellar environment. The findings of this statistical study will be reported in a follow-up paper.

Reliability Assessment of 3-D Space Frame Structures Applying Stochastic Finite Element Analysis

Throughout design development of satellite structure, stress engineer is usually challenged with randomness in applied loads and material properties. To overcome such problem, a risk-based design is applied which estimates satellite structure probability of failure under static and thermal loads. Determining probability of failure can help to update initially applied factors of safety that were used during structure preliminary design phase. These factors of safety are related to the satellite mission objective. Sensitivity-based analysis is to be implemented in the context of finite element analysis (probabilistic finite element method or stochastic finite element method (SFEM)) to determine the probability of failure for satellite structure or one of its components.

Cycle Ergometer Tests in Children With Cystic Fibrosis:Reliability and Feasibility

The aim of this study was to assess the reliability and feasibility of cycle ergometer tests in young children with cystic fibrosis (CF). Children with CF aged 6-11 years and with stable lung disease performed two cycle ergometry tests (intermittent sprint and continuous incremental) on two occasions 1 week apart. Reliability was assessed using repeated-measures ANOVA. Bias was considered to be significant at P?