Summary Immune responses involve coordination across cell types and tissues. However, studies in cancer immunotherapy have focused heavily on local immune responses in the tumor microenvironment. To investigate immune activity more broadly, we performed an organism-wide study in genetically-engineered cancer models using mass cytometry. We analyzed immune responses in several tissues after immunotherapy by developing intuitive models for visualizing single-cell data with statistical inference. Immune activation was evident in the tumor and systemically shortly after effective therapy was administered. However, during tumor rejection, only peripheral immune cells sustained their proliferation. This systemic response was coordinated across tissues and required for tumor eradication in several immunotherapy models. An emergent population of peripheral CD4 T cells conferred protection against new tumors and was significantly expanded in patients responding to immunotherapy. These studies demonstrate the critical impact of systemic immune responses that drive tumor rejection.

Context:Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers.Objectives:We aimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTCs).Design:This was a retrospective observational study.Setting and Patients:We studied 647 tumors and tumor-like lesions. A total of 469 patients with FCDTC treated and followed in five university hospitals were included. Mean follow-up (±SD) was 7.8 ± 5.8 years.Main Outcome Measures:Predictive value of TERT promoter mutations for distant metastasization, disease persistence at the end of follow-up, and disease-specific mortality.Results:TERT promoter mutations were found in 7.5% of papillary carcinomas (PTCs), 17.1% of follicular carcinomas, 29.0% of poorly differentiated carcinomas, and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumors were older (P < .001) and had larger tumors (P = .002). In DTCs, TERT promoter mutations were significantly associated with distant metastases (P < .001) and higher stage (P < .001). Patients with DTC harboring TERT promoter mutations were submitted to more radioiodine treatments (P = .009) with higher cumulative dose (P = .004) and to more treatment modalities (P = .001). At the end of follow-up, patients with TERT-mutated DTCs were more prone to have persistent disease (P = .001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P < .001)] in DTCs (P < .001), PTCs (P = .001), and follicular carcinomas (P < .001). After adjusting for age at diagnosis and gender, the hazard ratio was 10.35 (95% confidence interval 2.01–53.24; P = .005) in DTC and 23.81 (95% confidence interval 1.36–415.76; P = .03) in PTCs.Conclusions:TERT promoter mutations are an indicator of clinically aggressive tumors, being correlated with worse outcome and disease-specific mortality in DTC. TERT promoter mutations have an independent prognostic value in DTC and, notably, in PTC.

Purpose -The paper seeks to investigate the factors that affect the adoption of e-business by firms belonging to European Union (EU) countries, by comparing the effect across two different industries: telecommunications (telco) and tourism. Design/methodology/approach -Data were collected from 2,459 firms belonging to EU27 countries across two industries. The data were analyzed by employing factorial analysis and relevant hypotheses were derived and tested by logistic regression analysis. Findings -The results suggest that the perceived benefits and obstacles of e-business, technology readiness, competitive pressure, and trading partner collaboration are the drivers that are important for both industries. Through the comparison of the industries, statistically significant differences between the telco and the tourism industries, i.e. the relative importance of all drivers for e-business adoption differs between the industries, were found. The only exception is competitive pressure.Research limitations/implications -The cross-sectional nature of this paper does not allow knowing how this relationship will change overtime. Practical implications -The findings offer valuable insight to managerial and policy makers; they should promote information and communication technology infrastructure, information technology training programmes to employees, and trading partner collaboration with business partners in each industry mainly in the tourism industry. Originality/value -To the best of the authors' knowledge, this paper is one of the first that examines adoption of e-business with a multi-industries comparison of EU27 countries using a research model that combines the Tornatzky and Fleischer model and the Iacovou et al. model.

Family health: limits and possibilities for an integral primary healthcare approach in BrazilSaúde da família: limites e possibilidades para uma abordagem integral de atenção primária à saúde no Brasil

This study suggests that a pharmaceutical care program may provide important contributions to reduce haemoglobin A1C in type 2 diabetes patients. Moreover, the promotion of the rational use of drugs may be better achieved in a context of pharmaceutical care programs in Brazil.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of pre-existing subclones, remains unclear. In EGFR-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires AURKA activity. Non-genetic resistance through the activation of AURKA by its co-activator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in pre-clinical models. Treatment induced activation of AURKA was associated with resistance to EGFR inhibitors in-vitro, in-vivo and in individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA driven residual disease and acquired resistance.

In an aging society it is extremely important to develop devices, which can support and aid the elderly in their daily life. This demands means and tools that extend independent living and promote improved health. Thus, the goal of this article is to review the state of the art in the robotic technology for mobility assistive devices for people with mobility disabilities. The important role that robotics can play in mobility assistive devices is presented, as well as the identification and survey of mobility assistive devices subsystems with a particular focus on the walkers technology. The advances in the walkers' field have been enormous and have shown a great potential on helping people with mobility disabilities. Thus it is presented a review of the available literature of walkers and are discussed major advances that have been made and limitations to be overcome.

Analyses of forest loss and protected areas suggest that 36 to 57% of Amazonian tree flora may qualify as “globally threatened.”