State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)

PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy

Intention de chercher un emploi, théorie du comportement planifié, personnalité et expérience de la recherche d’emploi

International audienceThe present study aimed not only to confirm the paths between theory of planned behavior variables and job search intention with a French sample, but also to test the moderating effects of job search experience and two personality dimensions (extraversion and conscientiousness) on these paths. One hundred and fifty-four participants rated these concepts on a series of scales. Results showed that the theory of planned behavior variables were significantly related to job search intention, and that extraversion and conscientiousness moderated the paths between attitude and job search intention. Results are discussed with reference to the literature and their practical implications

A randomized, open-label, phase 2 study of everolimus in combination with pasireotide LAR or everolimus alone in advanced, well-differentiated, progressive pancreatic neuroendocrine tumors:COOPERATE-2 trial

Background : Several studies have demonstrated the antitumor activity of first-generation somatostatin analogs (SSAs), primarily targeting somatostatin receptor (sstr) subtypes 2 and 5, in neuroendocrine tumors (NET). Pasireotide, a second-generation SSA, targets multiple sstr subtypes. We compared the efficacy and safety of pasireotide plus everolimus to everolimus alone in patients with advanced, well-differentiated, progressive pancreatic NET. Patients and methods : Patients were randomized 1 : 1 to receive a combination of everolimus (10 mg/day, orally) and pasireotide long-acting release (60 mg/28 days, intramuscularly) or everolimus alone (10 mg/day, orally); stratified by prior SSA use, and baseline serum chromogranin A and neuron-specific enolase. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, objective response rate, disease control rate, and safety. Biomarker response was evaluated in an exploratory analysis. Results : Of 160 patients enrolled, 79 were randomized to the combination arm and 81 to the everolimus arm. Baseline demographics and disease characteristics were similar between the treatment arms. No significant difference was observed in PFS: 16.8 months in combination arm versus 16.6 months in everolimus arm (hazard ratio, 0.99; 95% confidence interval, 0.64–1.54). Partial responses were observed in 20.3% versus 6.2% of patients in combination arm versus everolimus arm; however, overall disease control rate was similar (77.2% versus 82.7%, respectively). No significant improvement was observed in median overall survival. Adverse events were consistent with the known safety profile of both the drugs; grade 3 or 4 fasting hyperglycemia was seen in 37% versus 11% of patients, respectively. Conclusions The addition of pasireotide to everolimus was not associated with the improvement in PFS compared with everolimus alone in this study. Further studies to delineate mechanisms by which SSAs slow tumor growth in NET are warranted

As mudanças nas regras da aposentadoria: os postos de trabalho estão adaptados à população que envelhece?

As mudanças nas regras de aposentadoria apontam para uma maior permanência dos idosos no mercado de trabalho. Esta permanência só se tornará viável caso haja mudanças nos postos de trabalho, tornando-os mais flexíveis e compatíveis com as características de uma população que envelhece. A partir de análises ergonômicas são apontadas algumas direções de pesquisas para a melhoria das condições de trabalho: concepção de dispositivos técnicos e organizacionais baseada na análise do trabalho real e uma política de formação contínua que permita aos trabalhadores permanecerem em atividade dentro do contexto atual de inovações tecnológicas.<br>The changes observed on the rules of retirement point out the increasing of the elderly's stay on the market. This stay will only be viable if there are also changes at the work stations, making them more flexible and compatible with the characteristics of a population that ages. Ergonomic analysis point out some directions of researches that can contribute to the improvement of work conditions: confections of technical and organizational provisions based on the analysis of the work how it's truly done and a politics of continuous formation that allows workers to stay actives on the actual context of technological innovations

Cultures matérielles

Cet ouvrage est destiné aux étudiants et chercheurs en anthropologie, sociologie, histoire, archéologie et à tous ceux qui œuvrent dans les domaines des techniques, du travail, de la communication ou de la psychologie. Ce large spectre est le produit de 35 années d’histoire de la revue, creuset d’idées et de méthodes testées au fil des ans sur les terrains ethnographiques et historiques les plus divers. Ce manuel comble une lacune sous une forme originale en regroupant des textes parfois inédits et introduits par les auteurs qui en expliquent l’actualité et le chemin parcouru depuis lors

ACCELERATE and European Medicine Agency Paediatric Strategy Forum for medicinal product development for mature B-cell malignancies in children.

Paediatric Strategy Forums have been created by the multistakeholder organisation, ACCELERATE, and the European Medicines Agency to facilitate dialogue between all relevant stakeholders and suggest strategies in critical areas of paediatric oncology drug development. As there are many medicines being developed for B-cell malignancies in adults but comparatively few in children with these malignancies, a Paediatric Strategy Forum was held to discuss the best approach to develop these products for children. It was concluded that as current frontline therapy is highly successful, despite associated acute toxicity, de-escalation of this or substitution of presently used drugs with new medicines can only be undertaken when there is an effective salvage regimen, which is currently not available. Therefore priority should be given to developing treatment for patients with relapsed and refractory mature B-cell lymphomas. The consensus of the clinicians attending the meeting was that CAR T-cells, T-cell engagers and antibody drug conjugates (excluding those with a vinca alkaloid–like drug) presently have the greatest probability of providing benefit in relapse in view of their mechanism of action. However, as producing autologous CAR T-cells currently takes at least 4 weeks, they are not products which could be quickly employed initially at relapse in rapidly progressing mature B-cell malignancies but only for the consolidation phase of the treatment. Global, industry-supported, academic-sponsored studies testing compounds from different pharmaceutical companies simultaneously should be considered in rare populations, and it was proposed that an international working group be formed to develop an overarching clinical trials strategy for these disease groups. Future Forums are planned for other relevant paediatric oncologic diseases with a high unmet medical need and relevant molecular targets.</p