Stock Market Reaction to the Global Financial Crisis: the Role of Corporate Governance and Product Quality Ratings in the Lehman Brothers' Event

We analyse with an event study approach the stock market reaction to one of the most important episodes in the global nancial crisis (Lehman Brothers ling for chapter 11). Our inquiry on abnormal returns of about 2,700 stocks around the event date documents that the shock induces investors to incorporate insights from (or re-adjust the pre-event expected impact of) corporate social responsibility (CSR) ratings in stock evaluation in a sort of "flight to CSR quality". The main CSR domains with signi cant effects on abnormal returns (corporate governance and product quality) are exactly those in which the defaulted company presented weaknesses according to its ex-ante CSR ratings. We also document that the reaction to the Lehman event extends beyond the event date and that investors rationally attribute more value to the direct information on strengths and weaknesses in each CSR rating domain than to aliation/non aliation to the CSR stock market index (FTSE KLD 400 Social Index). A more general result of our paper is that investors seem to discover, after the event, that CSR ratings provide original information which is not captured by traditional - nancial rating indicators.Global Financial Crisis; Event Study; Corporate Governance; Product Quality; Ratings.

Sistematização da atenção nutricional para pacientes críticos : uma proposição

Tese (doutorado)—Universidade de Brasília, Faculdade de Ciências da Saúde, Programa de Pós Graduação em Nutrição Humana, 2018.Introdução: A terapia nutricional é uma estratégia eficiente no combate à desnutrição, um mau presente em 30% a 60% dos pacientes na admissão hospitalar e que se intensificaria com a permanência nesse ambiente. A terapia nutricional precisa ser direcionada aos pacientes em risco, pois é onde ela se demonstra mais eficiente. Uma forma de identificar e monitorar esse grupo de pacientes é com a participação donutricionista na Equipe multiprofissional de terapia nutricional. Na EMTN o nutricionista pode implementar estratégias de triagem e avaliação nutricional validadas para sua população alvo, o que é sugerido por diretrizes, mas ainda não foi demonstrado como uma rotina efetiva na prática clínica. Objetivo: Esse estudo visou avaliar a eficácia da sistematização da atenção nutricional (triagem e avaliação nutricional) no reconhecimento de pacientes críticos em relação à mortalidade hospitalar. Materiais e Métodos: Na primeira fase da pesquisa, a amostra foi constituída por todos os hospitais públicos do Distrito Federal (n=7), com mais de 250 leitos. A performance da Equipe Multiprofissional em Terapia Nutricional foi avaliada por meio de um questionário estruturado com 54 questões, construído contemplando o conceito de qualidade em serviços de saúde proposto por Avendis Donabedian. A porcentagem de itens em conformidade foi utilizada para avaliar as diferenças sobre estrutura e processo entre hospitais com profissionais com dedicação exclusiva à EMTN e hospitais sem essa característica. Para analisar a associação entre triagem, avaliação nutricional e mortalidade hospitalar, foi conduzida uma coorte prospectiva com 327 pacientes admitidos em uma Unidade de Terapia Intensiva mista (72 leitos), no período de 2014 a 2016. Foram utilizados dados gerais registrados nos prontuários eletrônicos e também referentes à triagem nutricional (NRS 2002) e avaliação nutricional (método ANDASPEN). A predição de mortalidade hospitalar foi avaliada por meio de um modelo de regressão logística. Resultados: Neste processo, protocolos validados para triagem e avaliação nutricional foram considerados indicadores estruturais e a execução dessas atividades foi considerada indicador de processo. Verificou-se que indicadores de estrutura foram responsáveis por 68% da variabilidade de indicadores de processo relacionados a terapia nutricional (p-valor 0,013). No estudo de coorte, identificou-se que a triagem nutricional se associou com a desnutrição e a desnutrição aumentou em 2.37 vezes (IC 95 % de 1.29 – 4.27, p = 0.001) a chance de mortalidade hospitalar. Conclusão: Os dados obtidos evidenciaram que as etapas de triagem e avaliação nutricional, validadas para pacientes admitidos em UTI, podem atuar positivamente no reconhecimento de pacientes desnutridos e complementar uma cadeia de atenção para recuperar tais pacientes. Igualmente, os dados mostraram que, quando estas atividades foram executadas com ferramentas validadas, a triagem nutricional se associou com a avaliação nutricional e essa última com a mortalidade hospitalar.Introduction: Nutritional therapy is an effective strategy to fight against malnutrition, which prevalence ranges from 30% to 60% at hospital admission and it increases during hospital stay. Nutritional therapy needs to be targeted at risk patients because it is more efficient to them. One way to identify and monitor this group is to include the nutritionist in the Nutritional support team. There, the dietitian can implement a system of nutritional screening and patient assessment using validated routines, which are mentioned in many guidelines, but it is not strongly supported by studies and not demonstrated as an effective routine. Objective: This study aimed to evaluate the effectiveness of the systematization of the nutritional care (screening and nutritional assessment) in the recognition of mortality risk. Material and Methods: In the first phase of the research, the study sample consisted of all public hospitals in the Brazilian Federal District with more than 250 beds (n=7). The performance of the Nutrition Support Team was evaluated with an structured questionnaire with 54 questions, constructed in the light of the quality concept of Avendis Donabedian for health services. The percentage of items in accordance was used to evaluate the differences in structure and processes between hospitals with professionals exclusively to Nutrition Support Team and hospitals without this feature. To analyze the association between screening, nutritional assessment and hospital mortality, a prospective cohort was conducted with 327 patients admitted to a mixed intensive care unit (72 beds), from 2014 to 2016. General and nutritional data was recorded in the electronic health records such as screening (NRS 2002) and nutritional assessment (AND-ASPEN method). Hospital mortality prediction was assessed using a logistic regression model. Results: In this process, validated protocols for nutritional screening and evaluation were considered structural indicators and execution of these activities was considered a process indicator. We verified that structural indicators were responsible for 68% in the variability change in process indicators (p-value 0,013). In the cohort study, it was identified that nutritional screening was associated with malnutrition (OR 3.17; IC 95% 2.27 – 4.41; pvalue = 0,0001) and malnutrition increased the mortality by 2.37-fold (IC 95% 1.29 – 4.27, p-value = 0.001). Conclusions: The data obtained shows that validated nutritional screening and nutritional assessment for patients admitted to the ICU can act positively in the recognition of malnourished patients and complement a care chain to recover such patients. Likewise, the data shows that when these activities are performed with validated tools, nutritional screening is associated with nutritional assessment and the latter with hospital mortality

Validação de conteúdo de instrumento para Avaliar os procedimentos da nutrição enteral em ambiente hospitalar

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, Departamento de Nutrição, 2013.A Terapia Nutricional Enteral (TNE) é a primeira estratégia para enfrentar adesnutrição hospitalar. O Brasil foi um dos primeiros países latino-americanos adesenvolver legislação específica para a TNE. O controle da qualidade está nocentro dessa legislação assumindo papel essencial para assegurar a garantia daqualidade nutricional e sanitária. Todavia, observa-se uma lacuna quanto àexistência de instrumentos específicos para monitorar o controle da qualidade daTNE. O objetivo deste estudo foi construir e validar o conteúdo de um instrumentopara avaliar a qualidade da TNE, conforme a legislação brasileira, abordando amultidisciplinaridade, boas práticas, procedimentos operacionais padrão, aimplementação de protocolos e os registros destes procedimentos. A construção detal instrumento requereu a validação de seu conteúdo por meio de quatro etapas:pesquisa bibliográfica, opinião de especialistas (subjetiva), avaliação semântica eopinião de especialistas (objetiva). Na última etapa, dez especialistas opinaram,avaliando as ferramentas por quatro atributos: utilidade, simplicidade, objetividade ebaixo custo em uma escala Likert de 5 pontos (1-5). Como resultado, obteve-se uminstrumento constituído por três ferramentas independentes que, juntas,representam o processo de avaliação da TNE: Atividades da Equipe Multiprofissionalde Terapia Nutricional, Preparação de NE e Administração de NE. Todos os itensincluídos nesse instrumento obtiveram mais de 80% de consenso entre especialistasda área, o que caracteriza uma avaliação positiva do painel de especialistas. Assim,esse instrumento é de grande valia para avaliar a TN de hospitais, direcionarauditorias periódicas, ou ainda servir como check-list para instituir serviços de TNEem hospitais. ______________________________________________________________________________ ABSTRACTEnteral nutrition therapy (ENT) is the primary strategy available to fight againsthospital malnutrition. Brazil is one of the first Latin American countries to developlaws for enteral nutrition. Quality control is in the core of this legal instrument, playingan essential role to assure safety enteral nutrition therapy. Nowadays, tools toaccess quality control represent a gap in the area. The aim of this study was todevelop and proceed a content validation in a quality control tool, according toBrazilian law for enteral nutrition therapy, regarding multidisciplinary approach, goodpractices, standard operating procedures, protocol implementation, properregistration and electronic health record. A content validation method was utilized inthis four stages development process: bibliographic research, expert opinion(subjective), semantic evaluation and expert opinion (objective). In the latter stageten specialists, expressed their opinion evaluating the tools by four differentattributes: utility, simplicity, objective and low cost on a 5-point Likert scale (1-5). Weobtain as results three independent tools that together, represent the wholeevaluation process, named: Nutrition Support Team Activities, Enteral NutritionPreparation and Enteral Nutrition Administration. All of the items included in thisinstrument had at least 80% of approval in the specialist panel, what is considered apositive evaluation from the experts. This way, this instrument is considered to be ofgreat value to guide periodical audits in hospitals, or even to be utilized as checklistto implement a plan on enteral nutrition therapy

Voltage-gated Na+ Channel Activity Increases Colon Cancer Transcriptional Activity and Invasion Via Persistent MAPK Signaling

Functional expression of voltage-gated Na+ channels (VGSCs) has been demonstrated in multiple cancer cell types where channel activity induces invasive activity. The signaling mechanisms by which VGSCs promote oncogenesis remain poorly understood. We explored the signal transduction process critical to VGSC-mediated invasion on the basis of reports linking channel activity to gene expression changes in excitable cells. Coincidentally, many genes transcriptionally regulated by the SCN5A isoform in colon cancer have an over-representation of cis-acting sites for transcription factors phosphorylated by ERK1/2 MAPK. We hypothesized that VGSC activity promotes MAPK activation to induce transcriptional changes in invasion-related genes. Using pharmacological inhibitors/activators and siRNA-mediated gene knockdowns, we correlated channel activity with Rap1-dependent persistent MAPK activation in the SW620 human colon cancer cell line. We further demonstrated that VGSC activity induces downstream changes in invasion-related gene expression via a PKA/ERK/c-JUN/ELK-1/ETS-1 transcriptional pathway. This is the first study illustrating a molecular mechanism linking functional activity of VGSCs to transcriptional activation of invasion-related genes

Androgen Receptor-Target Genes in African American Prostate Cancer Disparities

The incidence and mortality rates of prostate cancer (PCa) are higher in African American (AA) compared to Caucasian American (CA) men. To elucidate the molecular mechanisms underlying PCa disparities, we employed an integrative approach combining gene expression profiling and pathway and promoter analyses to investigate differential transcriptomes and deregulated signaling pathways in AA versus CA cancers. A comparison of AA and CA PCa specimens identified 1,188 differentially expressed genes. Interestingly, these transcriptional differences were overrepresented in signaling pathways that converged on the androgen receptor (AR), suggesting that the AR may be a unifying oncogenic theme in AA PCa. Gene promoter analysis revealed that 382 out of 1,188 genes contained cis-acting AR-binding sequences. Chromatin immunoprecipitation confirmed STAT1, RHOA, ITGB5, MAPKAPK2, CSNK2A,1 and PIK3CB genes as novel AR targets in PCa disparities. Moreover, functional screens revealed that androgen-stimulated AR binding and upregulation of RHOA, ITGB5, and PIK3CB genes were associated with increased invasive activity of AA PCa cells, as siRNA-mediated knockdown of each gene caused a loss of androgen-stimulated invasion. In summation, our findings demonstrate that transcriptional changes have preferentially occurred in multiple signaling pathways converging (“transcriptional convergence”) on AR signaling, thereby contributing to AR-target gene activation and PCa aggressiveness in AAs

Alternative Splicing Promotes Tumour Aggressiveness and Drug Resistance in African American Prostate Cancer.

linical challenges exist in reducing prostate cancer (PCa) disparities. The RNA splicing landscape of PCa across racial populations has not been fully explored as a potential molecular mechanism contributing to race-related tumour aggressiveness. Here, we identify novel genome-wide, race-specific RNA splicing events as critical drivers of PCa aggressiveness and therapeutic resistance in African American (AA) men. AA-enriched splice variants of PIK3CD, FGFR3, TSC2 and RASGRP2 contribute to greater oncogenic potential compared with corresponding European American (EA)-expressing variants. Ectopic overexpression of the newly cloned AA-enriched variant, PIK3CD-S, in EA PCa cell lines enhances AKT/mTOR signalling and increases proliferative and invasive capacity in vitro and confers resistance to selective PI3Kδ inhibitor, CAL-101 (idelalisib), in mouse xenograft models. High PIK3CD-S expression in PCa specimens associates with poor survival. These results highlight the potential of RNA splice variants to serve as novel biomarkers and molecular targets for developmental therapeutics in aggressive PCa

Alternative Splicing Promotes Tumour Aggressiveness and Drug Resistance in African American Prostate Cancer.

linical challenges exist in reducing prostate cancer (PCa) disparities. The RNA splicing landscape of PCa across racial populations has not been fully explored as a potential molecular mechanism contributing to race-related tumour aggressiveness. Here, we identify novel genome-wide, race-specific RNA splicing events as critical drivers of PCa aggressiveness and therapeutic resistance in African American (AA) men. AA-enriched splice variants of PIK3CD, FGFR3, TSC2 and RASGRP2 contribute to greater oncogenic potential compared with corresponding European American (EA)-expressing variants. Ectopic overexpression of the newly cloned AA-enriched variant, PIK3CD-S, in EA PCa cell lines enhances AKT/mTOR signalling and increases proliferative and invasive capacity in vitro and confers resistance to selective PI3Kδ inhibitor, CAL-101 (idelalisib), in mouse xenograft models. High PIK3CD-S expression in PCa specimens associates with poor survival. These results highlight the potential of RNA splice variants to serve as novel biomarkers and molecular targets for developmental therapeutics in aggressive PCa

MicroRNAs Are Involved in the Development of Morphine-Induced Analgesic Tolerance and Regulate Functionally Relevant Changes in Serpini1.

Long-term opioid treatment results in reduced therapeutic efficacy and in turn leads to an increase in the dose required to produce equivalent pain relief and alleviate break-through or insurmountable pain. Altered gene expression is a likely means for inducing long-term neuroadaptations responsible for tolerance. Studies conducted by our laboratory (Tapocik et al., 2009) revealed a network of gene expression changes occurring in canonical pathways involved in neuroplasticity, and uncovered miRNA processing as a potential mechanism. In particular, the mRNA coding the protein responsible for processing miRNAs, Dicer1, was positively correlated with the development of analgesic tolerance. The purpose of the present study was to test the hypothesis that miRNAs play a significant role in the development of analgesic tolerance as measured by thermal nociception. Dicer1 knockdown, miRNA profiling, bioinformatics, and confirmation of high value targets were used to test the proposition. Regionally targeted Dicer1 knockdown (via shRNA) had the anticipated consequence of eliminating the development of tolerance in C57BL/6J (B6) mice, thus supporting the involvement of miRNAs in the development of tolerance. MiRNA expression profiling identified a core set of chronic morphine-regulated miRNAs (miR\u27s 27a, 9, 483, 505, 146b, 202). Bioinformatics approaches were implemented to identify and prioritize their predicted target mRNAs. We focused our attention on miR27a and its predicted target serpin peptidase inhibitor clade I (Serpini1) mRNA, a transcript known to be intricately involved in dendritic spine density regulation in a manner consistent with chronic morphine\u27s consequences and previously found to be correlated with the development of analgesic tolerance. In vitro reporter assay confirmed the targeting of the Serpini1 3′-untranslated region by miR27a. Interestingly miR27a was found to positively regulateSerpini1 mRNA and protein levels in multiple neuronal cell lines. Lastly, Serpini1 knockout mice developed analgesic tolerance at a slower rate than wild-type mice thus confirming a role for the protein in analgesic tolerance. Overall, these results provide evidence to support a specific role for miR27a and Serpini1 in the behavioral response to chronic opioid administration (COA) and suggest that miRNA expression and mRNA targeting may underlie the neuroadaptations that mediate tolerance to the analgesic effects of morphine

Alternative Splicing Promotes Tumour Aggressiveness and Drug Resistance in African American Prostate Cancer.

linical challenges exist in reducing prostate cancer (PCa) disparities. The RNA splicing landscape of PCa across racial populations has not been fully explored as a potential molecular mechanism contributing to race-related tumour aggressiveness. Here, we identify novel genome-wide, race-specific RNA splicing events as critical drivers of PCa aggressiveness and therapeutic resistance in African American (AA) men. AA-enriched splice variants of PIK3CD, FGFR3, TSC2 and RASGRP2 contribute to greater oncogenic potential compared with corresponding European American (EA)-expressing variants. Ectopic overexpression of the newly cloned AA-enriched variant, PIK3CD-S, in EA PCa cell lines enhances AKT/mTOR signalling and increases proliferative and invasive capacity in vitro and confers resistance to selective PI3Kδ inhibitor, CAL-101 (idelalisib), in mouse xenograft models. High PIK3CD-S expression in PCa specimens associates with poor survival. These results highlight the potential of RNA splice variants to serve as novel biomarkers and molecular targets for developmental therapeutics in aggressive PCa