Direct tumor recognition by a human CD4(+) T-cell subset potently mediates tumor growth inhibition and orchestrates anti-tumor immune responses.

Tumor antigen-specific CD4(+) T cells generally orchestrate and regulate immune cells to provide immune surveillance against malignancy. However, activation of antigen-specific CD4(+) T cells is restricted at local tumor sites where antigen-presenting cells (APCs) are frequently dysfunctional, which can cause rapid exhaustion of anti-tumor immune responses. Herein, we characterize anti-tumor effects of a unique human CD4(+) helper T-cell subset that directly recognizes the cytoplasmic tumor antigen, NY-ESO-1, presented by MHC class II on cancer cells. Upon direct recognition of cancer cells, tumor-recognizing CD4(+) T cells (TR-CD4) potently induced IFN-γ-dependent growth arrest in cancer cells. In addition, direct recognition of cancer cells triggers TR-CD4 to provide help to NY-ESO-1-specific CD8(+) T cells by enhancing cytotoxic activity, and improving viability and proliferation in the absence of APCs. Notably, the TR-CD4 either alone or in collaboration with CD8(+) T cells significantly inhibited tumor growth in vivo in a xenograft model. Finally, retroviral gene-engineering with T cell receptor (TCR) derived from TR-CD4 produced large numbers of functional TR-CD4. These observations provide mechanistic insights into the role of TR-CD4 in tumor immunity, and suggest that approaches to utilize TR-CD4 will augment anti-tumor immune responses for durable therapeutic efficacy in cancer patients.

Judicialisation and Direct Democracy. Switzerland's Ban on Minaret Construction

Launched by representatives from the Union démocratique du centre (UDC) with the aim of circumventing political and judicial decisions made at both local and national levels, the 2009 federal popular initiative calling for a ban on the construction of minarets rekindled the stigmatisation of Muslims living in Switzerland. Within the prevalent institutional configuration it moreover revived controversies surrounding issues such as direct democracy versus fundamental rights, or "the will of the people" versus "the power of the judges", whether national or international. "Judicialisation" is a polysemous concept. It is not understood here as the transfer to the courts of matters of political significance - in this instance the public regulation of religion - but as a process of juridification (or juridicalisation) in which court rulings were constantly anticipated in the political debate provoked by the popular initiative.

Sources of variability of speech, spatial, and qualities of hearing scale (SSQ) scores in normal-hearing and hearing-impaired populations.

OBJECTIVE: To identify and quantify sources of variability in scores on the speech, spatial, and qualities of hearing scale (SSQ) and its short forms among normal-hearing and hearing-impaired subjects using a French-language version of the SSQ. DESIGN: Multi-regression analyses of SSQ scores were performed using age, gender, years of education, hearing loss, and hearing-loss asymmetry as predictors. Similar analyses were performed for each subscale (Speech, Spatial, and Qualities), for several SSQ short forms, and for differences in subscale scores. STUDY SAMPLE: One hundred normal-hearing subjects (NHS) and 230 hearing-impaired subjects (HIS). RESULTS: Hearing loss in the better ear and hearing-loss asymmetry were the two main predictors of scores on the overall SSQ, the three main subscales, and the SSQ short forms. The greatest difference between the NHS and HIS was observed for the Speech subscale, and the NHS showed scores well below the maximum of 10. An age effect was observed mostly on the Speech subscale items, and the number of years of education had a significant influence on several Spatial and Qualities subscale items. CONCLUSION: Strong similarities between SSQ scores obtained across different populations and languages, and between SSQ and short forms, underline their potential international use.

L'utilisation des anticoagulants oraux directs chez les patients âgés : les limites de la médecine fondée sur les preuves [The use of the new direct oral anticoagulants among older subjects: The limits of the evidence-based medicine?].

The growing use of direct oral anticoagulants, in particular among older subjects, raises questions about the limits of the evidence-based medicine. The phase III studies that have validated the efficacy and the safety profile of these molecules (dabigatran, rivaroxaban, apixaban, edoxaban) in their both indications, the venous thromboembolic disease and the non-valvular atrial fibrillation raise concerns in four major fields: the financial support of pharmaceutical companies, the links of interest for many authors with the industry, the study design (exclusively non-inferiority studies), and the poor representativeness of the older subjects included. All these points are discussed, using data of sub-groups studies, post-marketing studies and recent meta-analysis. The lack of data for the very old subjects, with frailty or comorbidities, remains the main concern from these phase III studies.