An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper (R)

Background: Accurate determination of the predictive markers human epidermal growth factor receptor 2 (HER2/ERBB2), estrogen receptor (ER/ESR1), progesterone receptor (PgR/PGR), and marker of proliferation Ki67 (MKI67) is indispensable for therapeutic decision making in early breast cancer. In this multicenter prospective study, we addressed the issue of inter- and intrasite reproducibility using the recently developed reverse transcription-quantitative real-time polymerase chain reaction-based MammaTyper (R) test. Methods: Ten international pathology institutions participated in this study and determined messenger RNA expression levels of ERBB2, ESR1, PGR, and MKI67 in both centrally and locally extracted RNA from formalin-fixed, paraffin-embedded breast cancer specimens with the MammaTyper (R) test. Samples were measured repeatedly on different days within the local laboratories, and reproducibility was assessed by means of variance component analysis, Fleiss' kappa statistics, and interclass correlation coefficients (ICCs). Results: Total variations in measurements of centrally and locally prepared RNA extracts were comparable; therefore, statistical analyses were performed on the complete dataset. Intersite reproducibility showed total SDs between 0.21 and 0.44 for the quantitative single-marker assessments, resulting in ICC values of 0.980-0.998, demonstrating excellent agreement of quantitative measurements. Also, the reproducibility of binary single-marker results (positive/negative), as well as the molecular subtype agreement, was almost perfect with kappa values ranging from 0.90 to 1.00. Conclusions: On the basis of these data, the MammaTyper (R) has the potential to substantially improve the current standards of breast cancer diagnostics by providing a highly precise and reproducible quantitative assessment of the established breast cancer biomarkers and molecular subtypes in a decentralized workup.Peer reviewe

Alternative phenotypes of male mating behaviour in the two-spotted spider mite

Severe intraspecific competition for mates selects for aggressive individuals but may also lead to the evolution of alternative phenotypes that do not act aggressively, yet manage to acquire matings. The two-spotted spider mite, Tetranychus urticae, shows male mate-guarding behaviour and male–male combat for available females. This may provide opportunity for weaker males to avoid fighting by adopting alternative mating behaviour such as sneaker or satellite tactics as observed in other animals. We investigated male precopulatory behaviour in the two-spotted spider mite by means of video-techniques and found three types of male mating behaviour: territorial, sneaker and opportunistic. Territorial and sneaker males associate with female teleiochrysales and spend much time guarding them. Territorial males are easily disturbed by rival males and engage themselves in fights with them. However, sneaker males are not at all disturbed by rival males, never engage in fights and, strikingly, never face attack by territorial males. Opportunistic males wander around in search of females that are in the teleiochrysalis stage but very close to or at emergence. To quickly classify any given mate-guarding male as territorial or sneaker we developed a method based on the instantaneous response of males to disturbance by a live male mounted on top of a brush. We tested this method against the response of the same males to natural disturbance by two or three other males. Because this method proved to be successful, we used it to collect territorial and sneaker males, and subjected them to morphological analysis to assess whether the various behavioural phenotypes are associated with different morphological characters. However, we found no statistical differences between territorial and sneaker males, concerning the length of the first legs, the stylets, the pedipalps or the body. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10493-013-9673-y) contains supplementary material, which is available to authorized users

Emplacement and deformation of mesozoic Gabbros of the High Atlas (Morocco): paleomagnetism and magnetic fabrics

A paleomagnetic and magnetic fabric study is performed in Upper Jurassic gabbros of the central High Atlas (Morocco). These gabbros were emplaced in the core of preexisting structures developed during the extensional stage and linked to basement faults. These structures were reactivated as anticlines during the Cenozoic compressional inversion. Gabbros from 19 out of the 33 sampled sites show a stable characteristic magnetization, carried by magnetite, which has been interpreted as a primary component. This component shows an important dispersion due to postemplacement tectonic movements. The absence of paleoposition markers in these igneous rocks precludes direct restorations. A novel approach analyzing the orientation of the primary magnetization is used here to restore the magmatic bodies and to understand the deformational history recorded by these rocks. Paleomagnetic vectors are distributed along small circles with horizontal axes, indicating horizontal axis rotations of the gabbro bodies. These rotations are higher when the ratio between shales and gabbros in the core of the anticlines increases. Due to the uncertainties inherent to this work (the igneous bodies recording strong rotations), interpretations must be qualitative. The magnetic fabric is carried by ferromagnetic (s.s.) minerals mimicking the magmatic fabric. Anisotropy of magnetic susceptibility (AMS) axes, using the rotation routine inferred from paleomagnetic results, result in more tightly clustered magnetic lineations, which also become horizontal and are considered in terms of magma flow trend during its emplacement: NW-SE (parallel to the general extensional direction) in the western sector and NE-SW (parallel to the main faults) in the easternmost structures

Correlations between instructor’s caring behavior and nursing students’ caring behavior: an international study

Introduction: Theoretically, caring relationship between faculty – student generates a caring moment. However, there is a scarcity of empirical evidence about how caring interactions with faculty can enhance students’ caring outcomes. Aim: The aim of this study was to identify the levels of students’ and instructors’ caring behavior and to explore the correlations between instructors’ and students’ caring behavior. Methods: A descriptive, non – experimental design has been used in this study. Data collection was based on interviews using two standardized questionnaires; the Nursing Students’ Perception of Instructor Caring (NSPIC) and the Caring Behavior Inventory (CBI). Respondents were consisting of nursing students from identified schools and colleges of nursing in different countries. Data were analyzed with SPSS version 21.0. Results: The sample was consisted of 368 nursing students (91% female, 9% male) from seven countries (26% Philippines, 31.5% Greece, 1% Kenya, 0.5 Oman, 35.5% India, 5% Nigeria, 0.5% Saudi Arabia). Forty two percent of students are in the second year of studies, 13% in the third year and 45% in the fourth year. The mean score of NSPIC was 4.02±0.30 and the mean of CBI was4.56±0.13. The mean for each factor of NSPIC was 4.39±0.13 for the factor “instills confidence through caring”, 3.92±0.212 for “supportive learning climate”, 4.06±0.06 for “appreciation of life’s meaning”, 3.66±0.11 for “control versus flexibility” and 4.01±0.48 for “respectful sharing”. The mean for each factor of CBI was 4.63±0.11 for the factor “assurance”, 4.58±0.06 for “knowledge and skills”, 4.55±0.18 for “respectful” and 4.47±0.14 for “connectedness”. Correlation analysis showed statistically significance between relevant variables. Conclusions: Instructors’ caring behavior affects nursing students’ caring behavior. Through positive faculty modeling and role modeling, nursing students can be professionally trained to develop the competence of caring