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.

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.

Conflict, Transformation, and Former Loyalist Paramilitary Prisoners in Northern Ireland

Following the 1998 Belfast Agreement in Northern Ireland, levels of paramilitary violence have declined substantially. Among loyalists, the Ulster Volunteer Force (UVF) and associated Red Hand Commando (RHC) have formally renounced violence, and dissolved their 'military structures', and perhaps the most reticent of all of the major paramilitary groupings, the Ulster Defence Association (UDA), has taken on board the central tenets of conflict transformation, and 'stood down' all of its 'active service units' in the Ulster Freedom Fighters (UFF). Thus, paramilitary violence now is mainly confined to the activities of 'dissident' republican groups, notably the Real and Continuity IRAs, although low-level sectarian violence remains a problem. Such dramatic societal and political change has resulted in a focus on the roles of formal party political leadership as agents of social change. This gaze, however, tends to obscure other important events such as the efforts, structures and approaches taken at the grassroots level to uphold and sustain conflict transformation and to maintain a reduction in violence. This article provides analysis of the role played by former loyalist paramilitary combatants in conflict transformation, and draws on material obtained through significant access to those former paramilitaries engaged in processes of societal shifts. In both personal and structural terms there is evidence of former combatants working to diminish the political tensions that remain as a result of the long-term inter-communal hostility developed across decades of violence and conflict.

Towards an Acceptable Level of Violence: Institutional Lessons from Northern Ireland

Institutional and economic development has recently returned to the forefront of economic analysis. The use of case studies (both historical and contemporary) has been important in this revival. Likewise, it has been argued recently by economic methodologists that historical context provides a kind of ‘‘laboratory’’ for the researcher interested in real world economic phenomena. Counterterrorism economics, in contrast with much of the rest of the literature on terrorism, has all too rarely drawn upon detailed contextual case studies. This article seeks to help remedy this problem. Archival evidence, including previously unpublished material on the DeLorean case, is an important feature of this article. The article examines how an inter-related strategy, which traded-off economic, security, and political considerations, operated during the Troubles. Economic repercussions of this strategy are discussed. An economic analysis of technical and organizational change within paramilitarism is also presented. A number of institutional lessons are discussed including: the optimal balance between carrot versus stick, centralization relative to decentralization, the economics of intelligence operations, and tit-for-tat violence. While existing economic models are arguably correct in identifying benefits from politico-economic decentralization, they downplay the element highlighted by institutional analysis.

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