RHCG and TCAF1 promoter hypermethylation predicts biochemical recurrence in prostate cancer patients treated by radical prostatectomy

PURPOSE: The lack of biomarkers that can distinguish aggressive from indolent prostate cancer has caused substantial overtreatment of clinically insignificant disease. Here, by genome-wide DNA methylome profiling, we sought to identify new biomarkers to improve the accuracy of prostate cancer diagnosis and prognosis. EXPERIMENTAL DESIGN: Eight novel candidate markers, COL4A6, CYBA, TCAF1 (FAM115A), HLF, LINC01341 (LOC149134), LRRC4, PROM1, and RHCG, were selected from Illumina Infinium HumanMethylation450 BeadChip analysis of 21 tumor (T) and 21 non-malignant (NM) prostate specimens. Diagnostic potential was further investigated by methylation-specific qPCR analysis of 80 NM vs. 228 T tissue samples. Prognostic potential was assessed by Kaplan-Meier, uni- and multivariate Cox regression analysis in 203 Danish radical prostatectomy (RP) patients (cohort 1), and validated in an independent cohort of 286 RP patients from Switzerland and the U.S. (cohort 2). RESULTS: Hypermethylation of the 8 candidates was highly cancer-specific (area under the curves: 0.79-1.00). Furthermore, high methylation of the 2-gene panel RHCG-TCAF1 was predictive of biochemical recurrence (BCR) in cohort 1, independent of the established clinicopathological parameters Gleason score, pathological tumor stage, and pre-operative PSA (HR (95% confidence interval (CI)): 2.09 (1.26 - 3.46); P = 0.004), and this was successfully validated in cohort 2 (HR (95% CI): 1.81 (1.05 - 3.12); P = 0.032). CONCLUSION: Methylation of the RHCG-TCAF1 panel adds significant independent prognostic value to established prognostic parameters for prostate cancer and thus may help to guide treatment decisions in the future. Further investigation in large independent cohorts is necessary before translation into clinical utility

Compulsion to work or emancipation through work? Contribution to a debate on active employment policies

Em Portugal, a obrigação de os trabalhadores desempregados se manterem disponíveis para aceitarem um trabalho "conveniente" foi criada em 1985, mas só a partir de 1989 ela dá lugar a uma política mais clara de activação dos trabalhadores que estão a receber subsídio de desemprego. Mais recentemente, a partir de 1996, o Rendimento Mínimo Garantido veio obrigar os beneficiários dessa prestação a assumirem o compromisso expresso de se disponibilizarem para aceitar um trabalho ou uma acção de formação profissional. O texto discute o conceito de activação e avalia as medidas de política que têm procurado desenvolver essa filosofia em Portugal tendo em conta os contextos sociais e políticos da sua aplicação.In Portugal, the mandatory availability of unemployed workers to accept a "convenient" job was created in 1985, but only from 1989 onwards it has given rise to a clearer policy of activating workers on workfare. More recently, from 1996 on, the Rendimento Mínimo Garantido (Minimum Guaranteed Earnings) has forced the beneficiaries to be available to take a job or a professional training activity

What place for East and West? Discourses, reality and foreign and security policies of post-Yugoslav small states

This paper explores different and changing receptions and uses of ‘East’ and ‘West’ in the foreign policy discourses of Serbia and Croatia, as puzzling cases of state identity configuration. The author suggests and gives meaning to the conception of ‘small state reality’ and offers a perspective on the role of historical, contextual and situational elements of state identity in the understanding of foreign policy orientations and agency. The paper discusses the productive possibilities of such a reading in the light of the relational turn in small states’ literature and recent discussions about ‘non-Western’ international relations