Importância dos Sites das IESp para a Atração de Alunos em São Paulo: o caso dos discentes de Administração na Unip, Uninove e Anhanguera

Este estudo – considerando o contexto competitivo no qual as Instituições de Ensino Superior particulares (IESp) estão inseridas, principalmente no que tange o processo de atração de novos alunos por meio dos sites na internet – está consubstanciado na questão-problema: Será que os alunos ingressantes no curso de Administração, de algumas das maiores IESp atuantes na cidade de São Paulo, foram influenciados pelos sites das mesmas quando no processo de escolha da instituição a se matricular? Com isso, o objetivo do estudo é: Analisar a influência dos sites das IESp de grande porte Unip, Uninove e Anhanguera, sobre a decisão dos alunos ingressantes no curso de Administração no momento da escolha da instituição na cidade de São Paulo. O estudo é de natureza qualitativa, mesmo apresentando os dados dos 400 questionários válidos, em percentuais, pois, a intensão é promover compreensões que possam ir além da simples tabulação dos dados. O questionário contou com 29 indagações fechadas. Como resultado foi possível saber que: os sites das IESp exercem influência sobre a escolha dos prospects; os alunos consideram que informações relativas ao composto de marketing (curso, valor da mensalidade, localização do campus e condições promocionais) devem estar disponíveis nos sites; a opinião dos amigos é muito importante na escolha da instituição; as informações sobre o curso, disponíveis no site da IESp, foram suficientes para sanar as dúvidas de 69% dos alunos ingressantes no curso de Administração em 2015

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource

The evolution of non-small cell lung cancer metastases in TRACERx

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Assessing the Viability of Sub-Surface Drip Irrigation for Resource-Efficient Alfalfa Production in Central and Southern California

In California, alfalfa is grown on a large area ranging between 325,000 and 410,000 hectares and ranks among the thirstiest crops. While the hay production industry is often scrutinized for the large usage of the state’s agricultural water, alfalfa is a crucial feed-supplier for the livestock and dairy sectors, which rank among the most profitable commodity groups in the state. Sub-surface drip irrigation (SDI), although only practiced on approximately 2% of the alfalfa production area in California, is claimed to have the potential to significantly increase hay yield (HY) and water productivity (WP) compared with surface irrigation (SI). In 2014–2016 we interviewed a number of growers pioneering SDI for alfalfa production in Central and Southern California who reported that yield improvements in the order of 10–30% and water saving of about 20–30% are achievable in SDI-irrigated fields compared with SI, according to their records and perceptions collected over few years of experience. Results from our research on SDI at the University of California, Davis, revealed significantly smaller yield gain (~5%) and a slight increase of water use (~2–3%) that are similar to findings from earlier research studies. We found that most of the interviewed alfalfa producers are generally satisfied with their SDI systems, yet face some challenges that call for additional research and educational efforts. Key limitations of SDI include high investment costs, use of energy to pressurize water, the need for more advanced irrigation management skills, and better understanding of soil-water dynamics by farm personnel. SDI-irrigated fields also need accurate water monitoring and control, attentive prevention and repair of rodent damages, and careful salinity management in the root zone. In this paper we attempt to evaluate the viability of the SDI technology for alfalfa production on the basis of preliminary results of our research and extension activities, with focus on its water and energy footprints within the context of resource efficiency

Estratégia de Fomento à Cultura de Inovação: Uma Abordagem Sobre o Programa ALI do Sebrae/SP / Development Strategy for Innovation Culture: An Approach on the Program of ALI of Sebrae/SP

Na busca pela vantagem competitiva, as empresas provocam mudanças em seus produtos e serviços por meio de ações que ofereçam algum incremento esperando que estes sejam percebidos pelos clientes. Entretanto, essas ações – quando realizadas – são ocasionais e de baixo impacto, tendo como resultado a baixa ou nenhuma percepção dos benefícios, tanto por parte do empreendedor quanto dos clientes. Além disso, dado o possível fracasso nestas ações, o esforço, o tempo e os custos envolvidos acabam desmotivando o empreendedor e gerando uma cultura avessa à inovação, assim, nota-se baixa intenção em investir e promover uma cultura de inovação. Diante desse quadro este artigo pretende apresentar os desafios, bem como os meios para promover a cultura da inovação nas micro e pequenas empresas, demonstrando os requisitos para a implementação da cultura de inovação. Busca ainda oferecer aos leitores um novo olhar acerca da prática da inovação, rompendo paradigmas e identificando possibilidades de melhoria, gerando novas oportunidades para os negócios. Para elaboração deste estudo foram realizadas pesquisas bibliográficas e documentais que mostram os fatores críticos que evidenciam a implementação da cultura da inovação, além de um exemplo prático de aplicação contemplado no programa, Agentes Locais de Inovação (ALI) desenvolvidos pelo SEBRAE. Palavras-chave: Cultura De Inovação. Cultura Organizacional. Estratégia. Inovação. Vantagem Competitiva. ABSTRACT In the quest for competitive advantage, companies cause changes in its products and services through actions that provide some increase waiting that they are perceived by customers, however, these actions - when held - are occasional and low-impact, resulting in the low or no perceived benefits, both by the entrepreneur as customers. In addition, given the possible failure in these actions, effort, time and costs involved demotivate the entrepreneur and creating a culture averse to innovation, as well, there is low intention to invest and promote a culture of innovation. Given this situation this article aims to present the challenges and the means to promote the culture of innovation in micro and small enterprises, showing the requirements for implementation of the culture of innovation, and offers readers a new perspective on the practice of innovation, breaking paradigms and identifying improvement opportunities, generating new opportunities for business. To prepare this study were carried out bibliographic and documentary research showing the critical factors that show the implementation of the culture of innovation, and a practical example of application contemplated in the program Agents Innovation Sites (ALI) developed by SEBRAE. Keywords: Innovation Culture. Organizational Culture. Strategy. Innovation. Competitive Advantage

Real-time ed end-point Polymerase Chain Reaction per la quantizzazione del DNA di Citomegalovirus: confronto tra metodi e con il test per l’antigene pp65

Quantitave Polymerase Chain Reaction (PCR) for Cytomegalovirus (CMV) DNA provides highly sensitive and specific data for detecting CMV as well as monitoring the infection and determining the appropriate antiviral strategy.To determine the clinical application of a recently introduced real-time (RT) PCR assay for CMV DNA quantitation in peripheral blood leukocytes (PBLs) and defining its correlation with the commercial quantitative end-point (EP) PCR method COBAS AMPLICOR CMV Monitor and pp65 antigen test. Sequential PBL samples (n=158) from 32 liver transplanted patients with CMV asymptomatic infection and positive for CMV DNA by EP-PCR were retrospectively analysed with RT-PCR and studied according to pp65 antigen levels. A good correlation was found between RT-PCR and pp65 antigen test (r=0.691) and between the two PCR assays (r=0.761). RT-PCR data were significantly higher in pre-emptive treated patients (those with >20 pp65+positive cells, median value: 3.8 log10 copies/500,000 PBLs) than in not-treated ones (2.9 logs).According to pp65 levels of 0, 1-10, 11-20, 21-50, 51-100 and >100 positive cells/200,000 PBLs, median CMV DNA load by RT-PCR was 2.6, 3.0, 3.6, 4.0. 4.2 and 4.8, log10 copies/ 500,000 PBLs, respectively (EP-PCR CMV DNA levels: 2. 8, 2.9, 3.8, 3.7, 3.9 and 4.0 logs). For samples with >20 pp65+cells, that is above the level at which pre-emptive therapy was started, RT-PCR values were significantly higher than in groups with less than 20 pp65+cells, whereas EP-PCR values did not significantly differ and showed a slower progression rate. Dilutions of DNA from CMV AD169 strain were used to probe RT-PCR reproducibility (between and intra-assay variability < 2%) and sensitivity (100% detection rate at 10 copies/reaction, 28.5% with EP-PCR). A significant improvement is coming from the introduction of RT-PCR to the study of CMV DNA dynamics in differently CMV infected patients due to a more reliable quantitation of CMV DNA for moderate and high DNA level compared to EP-PCR with better sensitivity and specificity. RTPCR gives more precise informations on viral load kinetics for evaluating the infection progress and assessing antiviral response, significantly simplifying and accelerating the process of producing a reliable quantification of CMV DNA for clinical purposes

Digital Communication and a Concern with the Community: A Case Study in a Cooperative Credit Araguaina, Brazil

This article seeks to address the attributes of Digital Communication used by a cooperative of Credit to meet the seventh cooperative principle of Concern for Community. The same occurred in a credit union in the city of Araguaina Tocantins, with the aim of identifying the digital communication developed by the cooperative. The article begins with a literature review on the emergence of cooperative, then the conceptualization of the credit union and its history in Brazil, then the cooperative principles and their evolution, conceptualizations of concern for the community, digital communication, social marketing and the presentation and analysis of results. The methodology was based on the case study, which according to Yin (2001) it is important because it is the reality studied. The research showed that the performance of the cooperative is geared entirely to their members and do not have a lot of focus related to social actions, but it promotes actions to attract members and to promote community development through digital media. Another important result of the research was that the principle addressed is one of the goals of the cooperative that aims to meet the interests, promote the welfare of members and the entire community where the cooperative operates