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.

Building legitimacy by criticising the pharmaceutical industry: a qualitative study among prescribers and local opinion leaders.

PRINCIPLES: The literature has described opinion leaders not only as marketing tools of the pharmaceutical industry, but also as educators promoting good clinical practice. This qualitative study addresses the distinction between the opinion-leader-as-marketing-tool and the opinion-leader-as-educator, as it is revealed in the discourses of physicians and experts, focusing on the prescription of antidepressants. We explore the relational dynamic between physicians, opinion leaders and the pharmaceutical industry in an area of French-speaking Switzerland. METHODS: Qualitative content analysis of 24 semistructured interviews with physicians and local experts in psychopharmacology, complemented by direct observation of educational events led by the experts, which were all sponsored by various pharmaceutical companies. RESULTS: Both physicians and experts were critical of the pharmaceutical industry and its use of opinion leaders. Local experts, in contrast, were perceived by the physicians as critical of the industry and, therefore, as a legitimate source of information. Local experts did not consider themselves opinion leaders and argued that they remained intellectually independent from the industry. Field observations confirmed that local experts criticised the industry at continuing medical education events. CONCLUSIONS: Local experts were vocal critics of the industry, which nevertheless sponsor their continuing education. This critical attitude enhanced their credibility in the eyes of the prescribing physicians. We discuss how the experts, despite their critical attitude, might still be beneficial to the industry's interests.

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.

The transatlantic business community faced with US direct investment in Western Europe, 1958-1968

This article examines the position of US and European business in the debate about American direct investment in Western Europe in a historical perspective, from the establishment of the Common Market to the introduction of US regulation of foreign direct investment (FDI) a decade later. Based on abundant and diverse archival documents, it sheds new light on the process of Americanisation and contributes to existing research on transnational networks, by revealing the active role industrial leaders on both sides of the Atlantic played in shaping the political responses to problems raised by the American firms' massive presence in the Common Market.

Transcranial Direct Current Stimulation for the Treatment of Chronic Tinnitus: A Randomized Controlled Study.

BACKGROUND: Tinnitus is an often disabling condition for which there is no effective therapy. Current research suggests that tinnitus may develop due to maladaptive plastic changes and altered activity in the auditory and prefrontal cortex. Transcranial direct current stimulation (tDCS) modulates brain activity and has been shown to transiently suppress tinnitus in trials. OBJECTIVE: To investigate the efficacy and safety of tDCS in the treatment of chronic subjective tinnitus. METHODS: In a randomized, parallel, double-blind, sham-controlled study, the efficacy and safety of cathodal tDCS to the auditory cortex with anode over the prefrontal cortex was investigated in five sessions over five consecutive days. Tinnitus was assessed after the last session on day 5, and at follow-up visits 1 and 3 months post stimulation using the Tinnitus Handicap Inventory (THI, primary outcome measure), Subjective Tinnitus Severity Scale, Hospital Anxiety and Depression scale, Visual Analogue Scale, and Clinical Global Impression scale. RESULTS: 42 patients were investigated, 21 received tDCS and 21 sham stimulation. There were no beneficial effects of tDCS on tinnitus as assessed by primary and secondary outcome measures. Effect size assessed with Cohen's d amounted to 0.08 (95% CI: -0.52 to 0.69) at 1 month and 0.18 (95% CI: -0.43 to 0.78) at 3 months for the THI. CONCLUSION: tDCS of the auditory and prefrontal cortices is safe, but does not improve tinnitus. Different tDCS protocols might be beneficial.

Marketing territorial et branding territorial : une revue de littérature systématique

Le présent article offre un aperçu systématique et complet de la littérature scientifique dédiée au domaine d'étude du marketing territorial et du branding territorial. 1172 contributions publiées entre 1976 et 2016 dans 98 revues différentes y sont analysées à l'aide d'un classement méticuleux dans des catégories et sous-catégories en fonction de l'approche disciplinaire, de la méthode utilisée et de la perspective adoptée. Cette revue de la littérature permet ainsi une vue d'ensemble détaillée de l'état de l'art et fait part des diverses tendances et évolutions concernant ce domaine d'étude en émergence. Elle atteste, entre autres, l'existence d'un flou conceptuel, de définitions divergentes et de faibles assises théoriques : ce qui contribue à un spectre très large d'objets d'étude. Un manque de preuves empiriques et de contributions à caractère explicatif est également observé : les nombreux postulats sur les effets des activités de marketing territorial par rapport à l'attractivité restent à démontrer. Elle souligne aussi un certain désintérêt de la littérature pour le contexte politico-institutionnel dans lequel les territoires s'inscrivent, pourtant crucial en termes de management public. Par ailleurs, ce travail souligne la place importante attribuée à la rhétorique des consultants, avec la publication d'une grande quantité de contributions normatives dans une optique de partage de bonnes pratiques. Pour finir, cette étude constate la présence d'un nombre significatif d'articles critiques.

Détermination du coût direct lors d'une procédure de cathétérisation d'une angioplastie avec ou sans pose de stent au CHUV

Cette étude consiste à comparer les coûts de deux procédures de dilatation artérielle coronaire (angioplastie par ballonet et angioplastie avec pose de stent) uniquement lors de la phase de cathérisation (et non pas de l'ensemble des coûts du séjour hospitalier). La première partie traite de l'importance de la maladie coronarienne, de ses traitements et des objectifs de l'étude. La deuxième partie explique les éléments et la méthode qui composent le calcul des coûts, illustre les résultats et compare les résultats des deux procédures. La troisième partie analyse les résultats en identifiant quels types de coûts sont à l'origine de la différence du coût total et en explicitant les limites et les compléments nécessaires à l'étude.