Safety, Efficacy, and Immunogenicity of Therapeutic Vaccines for Patients with High-Grade Cervical Intraepithelial Neoplasia (CIN 2/3) Associated with Human Papillomavirus: A Systematic Review.

Despite the knowledge that HPV is responsible for high-grade CIN and cervical cancer, little is known about the use of therapeutic vaccines as a treatment. We aimed to synthesize and critically evaluate the evidence from clinical trials on the safety, efficacy, and immunogenicity of therapeutic vaccines in the treatment of patients with high-grade CIN associated with HPV. A systematic review of clinical trials adhering to the PRISMA 2020 statement in MEDLINE/PubMed, Embase, CENTRAL Cochrane, Web of Science, Scopus, and LILACS was undertaken, with no data or language restrictions. Primary endpoints related to the safety, efficacy, and immunogenicity of these vaccines were assessed by reviewing the adverse/toxic effects associated with the therapeutic vaccine administration via histopathological regression of the lesion and/or regression of the lesion size and via viral clearance and through the immunological response of individuals who received treatment compared to those who did not or before and after receiving the vaccine, respectively. A total of 1184 studies were identified, and 16 met all the criteria. Overall, the therapeutic vaccines were heterogeneous regarding their formulation, dose, intervention protocol, and routes of administration, making a meta-analysis unfeasible. In most studies (n = 15), the vaccines were safe and well tolerated, with clinical efficacy regarding the lesions and histopathological regression or viral clearance. In addition, eleven studies showed favorable immunological responses against HPV, and seven studies showed a positive correlation between immunogenicity and the clinical response, indicating promising results that should be further investigated. In summary, therapeutic vaccines, although urgently needed to avoid progression of CIN 2/3 patients, still present sparse data, requiring greater investments in a well-designed phase III RCT.

Educational intervention about airway obstructions for early childhood teachers: a quasi-experimental study.

OBJECTIVE: To verify the effect of an educational intervention about airway obstructions and an airway clearing technique in teachers from Municipal Child Education Centers in a municipality in western Paraná. METHOD: A quasi-experimental pre- and post-test study. Data was collectedusing a questionnaire with thirty questions to assess knowledge about the subject. For the analyses, the chi-square and McNemar tests were used, withanα = 5% of significance. RESULTS: After the training sessions, there was a 16.22% increase in the number of correct answers to the questions dealing with the recognition of the obstruction (<0.0001) and the airway clearance technique (<0.0001). CONCLUSION: The intervention improved the knowledge of early childhood teachers in the municipality regarding the identification of airway obstruction and techniquesairway clearing in school-age children.

Educational intervention about airway obstructions for early childhood teachers: a quasi-experimental study / Intervención educativa sobre la obstrucción de las vías respiratorias para profesores de educación de la primera infancia: estudio casi experimental / Intervenção educativa sobre obstrução das vias respiratórias para professores de educação infantil: estudo quase-experimental

ABSTRACT Objective: To verify the effect of an educational intervention about airway obstructions and an airway clearing technique in teachers from Municipal Child Education Centers in a municipality in western Paraná. Method: A quasi-experimental pre- and post-test study. Data was collectedusing a questionnaire with thirty questions to assess knowledge about the subject. For the analyses, the chi-square and McNemar tests were used, withanα = 5% of significance. Results: After the training sessions, there was a 16.22% increase in the number of correct answers to the questions dealing with the recognition of the obstruction (<0.0001) and the airway clearance technique (<0.0001). Conclusion: The intervention improved the knowledge of early childhood teachers in the municipality regarding the identification of airway obstruction and techniquesairway clearing in school-age children.

RESUMEN Objetivo: Verificar el efecto de una intervención educativa sobre la obstrucción de las vías aéreas y una técnica de desobstrucción en docentes de Centros Municipales de Educación Infantil de un municipio del oeste de Paraná. Método: Estudio cuasiexperimental del tipo pre y postest. Se recolectó a los datos a través de un cuestionario con treinta preguntas para evaluar el conocimiento sobre el tema. Para los análisis se utilizaron las pruebas chi-cuadrado y McNemar, con α = 5% de significación. Resultados: Después del entrenamiento, hubo un aumento del 16,22% en el número de respuestas correctas a las preguntas relacionadas con el reconocimiento de la obstrucción (<0,0001) y la técnica de desobstrucción de la vía aérea (<0,0001). Conclusión: La intervención mejoró el conocimiento de los docentes de los centros municipales de educación infantil en cuanto a la identificación y técnica de desobstrucción de las vías respiratorias en niños en edad escolar.

RESUMO Objetivo: Verificar o efeito de uma intervenção educativa sobre a obstrução de vias aéreas e a técnica de desobstrução, em professores de Centros Municipais de Educação Infantil de um município do Oeste do Paraná. Método: Estudo quase-experimental do tipo pré e pós-teste. Os dados foram coletados por meio de um questionário com trinta questões para avaliar o conhecimento sobre a temática. Para as análises utilizou-se os testes de Qui-quadrado e McNemar, com α = 5% de significância. Resultados: Após o treinamento, houve o aumento de 16,22% no número de acertos das questões que tratavam do reconhecimento da obstrução (<0,0001) e da técnica de desobstrução das vias aéreas (<0,0001). Conclusão: A intervenção melhorou o conhecimento dos professores dos Centros Municipais de Educação Infantil, quanto a identificação e a técnica de desobstrução das vias aéreas em crianças de idade escolar.

Safety, efficacy and immunogenicity of therapeutic vaccines in the treatment of patients with high-grade cervical intraepithelial neoplasia associated with human papillomavirus: a systematic review protocol.

INTRODUCTION: Eighty per cent of the sexually active population will get human papillomavirus (HPV) infection, which is the most prevalent sexually transmitted disease worldwide. Persistence of high-grade HPV infection may evolve to a cervical intraepithelial neoplasia (CIN), and these lesions may be precursors of cervical cancer. However, this progression can be prevented by the administration of therapeutic vaccines which use the main oncoproteins responsible for cancer development in an attempt to trigger a more specific and effective immunological response against this disorder. We aim to evaluate the safety, efficacy and immunogenicity of therapeutic vaccines in the treatment of patients with high-grade CIN 2/3 associated with HPV. METHODS AND ANALYSIS: A systematic review of clinical trials will be undertaken. Medline, Excerpta Medica Database, Cochrane Central Register of Controlled Trials, Web of Science, Latin American and Caribbean Health Sciences Literature, Scientific Electronic Library Online and Scopus will be searched, with no restriction regarding publication date. Primary outcomes will include measures related to safety, efficacy and the immunogenicity of the therapeutic vaccines used in these patients. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methodological appraisal of the studies will be assessed by the Cochrane Risk-of-Bias Tool for randomised controlled trials, and the quality evidence of the risk of bias in single studies will be evaluated by Grading of Recommendations Assessment, Development and Evaluation. A narrative synthesis will be done for all included studies. Outcomes will be analysed according to the subgroups of HPV type, CIN grade, route of vaccine administration and vaccine type. Also, if sufficient data are available, a meta-analysis will be conducted. The effect sizes will be generated using Hedges' g score for both fixed and random effect models. I 2 statistics will be used to assess heterogeneity and identify their potential sources. ETHICS AND DISSEMINATION: Ethical approval is not required as primary data will not be collected. Findings will be disseminated widely via peer-reviewed publication and in different media, for example, conferences, congresses or symposia. PROSPERO REGISTRATION NUMBER: CRD42017077428.

Punishment and the potential for negative reinforcement with histamine injection.

The present study examined punishment of responding with histamine injection, and its potential to generate avoidance of punishment. Sprague-Dawley rats were trained under concurrent schedules in which responses on one lever (the punishment lever) produced food under a variable-interval schedule, and under some conditions intermittent injections of histamine, which suppressed behavior. Responses on a second (avoidance) lever prevented histamine injections scheduled on the punishment lever. After stabilization of punished responding, a variable-interval 15-s schedule of cancellation of histamine (avoidance) was added for responding on the second/avoidance lever, without subsequent acquisition of responding on that lever. Progressive decreases in the length of the punishment variable-interval schedule increased suppression on the punishment lever without increases in response rates on the avoidance lever. Exchanging contingencies on the levers ensured that response rates on the avoidance lever were sufficiently high to decrease the histamine injection frequency; nonetheless response rates on the avoidance lever decreased over subsequent sessions. Under no condition was responding maintained on the avoidance lever despite continued punishing effectiveness of histamine throughout. The present results suggest that avoidance conditioning is not a necessary condition for effective punishment, and confirm the importance of empirical rather than presumed categorization of behavioral effects of stimulus events.

Assessment of Primary Health Care in the Treatment of Tuberculosis in a Brazilian Locality of the International Triple Frontier.

OBJECTIVE: To evaluate the performance of Primary Health Care (PHC) in treatment of TB patients in a triple international border municipality. METHODS: The present study was an evaluative survey of cross-sectional and quantitative approach conducted with 225 PHC healthcare professionals. Data was collected through a structured and validated instrument, which provided five indicators of "structure" and four indicators of "process" classified as unsatisfactory, regular or satisfactory. RESULTS: The "structure" component was unsatisfactory for the indicator of professionals involved in TB care and training, and regular for the indicator of connection between the units and other levels of care. The "process" component was regular for the indicators of TB information, directly observed treatment and reference and counter reference on TB, and unsatisfactory for external actions on TB control. CONCLUSION: The "structure" and "process" components points out some weaknesses in terms of management and organization of human resources. Low frequency of training and the turnover influenced the involvement of professionals. Elements of "structure" and "process" show the need for investing in the PHC team and improving the clinical management of cases.

Walden Two: Uma sociedade utópica não aversiva? / Walden Two: A non-aversive utopian society?

A ficção Walden Two (Skinner, 1948/1975) retrata uma sociedade cujas práticas sociais são baseadas em princípios científicos da Análise do Comportamento. A proposta envolve basicamente o uso de reforço positivo em contraste, com as sociedades reais, nas quais o controle aversivo seria um traço quase onipresente. Seria Walden Two de fato uma sociedade culturalmente planejada apenas em contingências de reforçamento positivo? O controle aversivo estaria ausente das relações sociais? O presente trabalho teve como objetivo geral investigar sistematicamente a presença ou não de controle aversivo no livro Walden Two. A obra foi examinada identificando-se os trechos que continham palavras-chave relacionadas ao controle aversivo. Observou-se que em três momentos específicos o controle aversivo é prescrito. Discute-se o uso inapropriado de Walden Two como um representante de uma sociedade não coercitiva assim como a necessidade de se reavaliar o papel (científico e ético) do próprio controle aversivo nas relações sociais, planejadas ou não.(AU)

The fiction novel Walden Two (Skinner, 1948/1975) depicts a society in which the social practices are based in the scientific principles of Behavior Analysis. It involves, basically, the use of positive reinforcement, in contrast to the real societies where aversive control is ubiquitous. Would ‘Walden Two’ really be a culturally planned society based strictly on positive reinforcement contingencies? The present essay is a systematic investigation of the presence or absence of aversive control in Walden Two. The novel was examined, identifying excerpts with key words related to aversive control. Three specific situations were identified, described and analyzed. We argue the inappropriate use of Walden Two as a model of non-coercive society and the need of reevaluating the role of aversive control itself in social relationships, planned or not.(AU)

Walden Two: uma sociedade utópica não aversiva? / Walden Two: a non-aversive utopian society?

A ficção Walden Two (Skinner, 1948/1975) retrata uma sociedade cujas práticas sociais são baseadas em princípios científicos da Análise do Comportamento. A proposta envolve basicamente o uso de reforço positivo em contraste, com as sociedades reais, nas quais o controle aversivo seria um traço quase onipresente. Seria Walden Two de fato uma sociedade culturalmente planejada apenas em contingências de reforçamento positivo? O controle aversivo estaria ausente das relações sociais? O presente trabalho teve como objetivo geral investigar sistematicamente a presença ou não de controle aversivo no livro Walden Two. A obra foi examinada identificando-se os trechos que continham palavras-chave relacionadas ao controle aversivo. Observou-se que em três momentos específicos o controle aversivo é prescrito. Discute-se o uso inapropriado de Walden Two como um representante de uma sociedade não coercitiva assim como a necessidade de se reavaliar o papel (científico e ético) do próprio controle aversivo nas relações sociais, planejadas ou não.

The fiction novel Walden Two (Skinner, 1948/1975) depicts a society in which the social practices are based in the scientific principles of Behavior Analysis. It involves, basically, the use of positive reinforcement, in contrast to the real societies where aversive control is ubiquitous. Would ‘Walden Two’ really be a culturally planned society based strictly on positive reinforcement contingencies? The present essay is a systematic investigation of the presence or absence of aversive control in Walden Two. The novel was examined, identifying excerpts with key words related to aversive control. Three specific situations were identified, described and analyzed. We argue the inappropriate use of Walden Two as a model of non-coercive society and the need of reevaluating the role of aversive control itself in social relationships, planned or not.

B. F. Skinner e o uso do controle aversivo: um estudo conceitual / B. F. Skinner and the use of aversive control: a conceptual study

B. F. Skinner (1904-1990) é frequentemente citado como representante de um posicionamento contrário ao uso de controle aversivo. Entretanto, observa-se certa divergência, na literatura comportamental, quanto à postura de Skinner a esse respeito. O presente trabalho teve como objetivo identificar e analisar em quais momentos Skinner prescreve ou adverte sobre o uso do controle aversivo. Um estudo conceitual foi realizado, no qual oito obras (Skinner 1938/1991; 1948/1975; 1953/1989; 1968/1972; 1969/1980; 1971; 1974/2006; 1989) foram analisadas conforme as categorias: 1) a definição de controle aversivo e conceitos envolvidos; 2) os aspectos negativos do controle aversivo e proibições; e 3) os aspectos positivos do controle aversivo e prescrições. Por fim, não foi possível encontrar uma definição específica de controle aversivo, e constatou-se que em determinados momentos Skinner justifica o uso deste tipo de controle, mas não o prescreve genericamente.(AU)

B. F. Skinner (1904-1990) is frequently cited as having a contrary position on the use of aversive control. However, in certain passages Skinner presents a more flexible opinion about the use of this type of behavioral control. The purpose of the present study was to identify and analyze the passages where Skinner prescribes or warns about such use. A conceptual study was conducted involving eight Skinner works (Skinner 1938/1991, 1948/1975, 1953/1989, 1968/1972, 1969/1980, 1971, 1974/2006, 1989), analyzed according to the following categories: 1) the definition of aversive control and concepts involved; 2) the negative aspects of aversive control and prohibitions; and 3) the positive aspects of aversive control and its recommendations. It wasn't possible to find a specific definition of aversive control and it was observed that at certain moments Skinner justifies the use of aversive control, but does not prescribe it in general.(AU)

B. F. Skinner e o uso do controle aversivo: um estudo conceitual / B. F. Skinner and the use of aversive control: a conceptual study

B. F. Skinner (1904-1990) é frequentemente citado como representante de um posicionamento contrário ao uso de controle aversivo. Entretanto, observa-se certa divergência, na literatura comportamental, quanto à postura de Skinner a esse respeito. O presente trabalho teve como objetivo identificar e analisar em quais momentos Skinner prescreve ou adverte sobre o uso do controle aversivo. Um estudo conceitual foi realizado, no qual oito obras (Skinner 1938/1991; 1948/1975; 1953/1989; 1968/1972; 1969/1980; 1971; 1974/2006; 1989) foram analisadas conforme as categorias: 1) a definição de controle aversivo e conceitos envolvidos; 2) os aspectos negativos do controle aversivo e proibições; e 3) os aspectos positivos do controle aversivo e prescrições. Por fim, não foi possível encontrar uma definição específica de controle aversivo, e constatou-se que em determinados momentos Skinner justifica o uso deste tipo de controle, mas não o prescreve genericamente.

B. F. Skinner (1904-1990) is frequently cited as having a contrary position on the use of aversive control. However, in certain passages Skinner presents a more flexible opinion about the use of this type of behavioral control. The purpose of the present study was to identify and analyze the passages where Skinner prescribes or warns about such use. A conceptual study was conducted involving eight Skinner works (Skinner 1938/1991, 1948/1975, 1953/1989, 1968/1972, 1969/1980, 1971, 1974/2006, 1989), analyzed according to the following categories: 1) the definition of aversive control and concepts involved; 2) the negative aspects of aversive control and prohibitions; and 3) the positive aspects of aversive control and its recommendations. It wasn't possible to find a specific definition of aversive control and it was observed that at certain moments Skinner justifies the use of aversive control, but does not prescribe it in general.

Construção terminológica e conceitual do controle aversivo: período Thorndike-Skinner e algumas divergências remanescentes / Terminological and conceptual construction of the aversive control: Thorndike-Skinner period and some remaining divergences

Neste ensaio, procura-se apresentar alguns aspetos históricos relevantes da construção terminológica e conceitual do controle aversivo. Foram descritos alguns tópicos do período que vai de Thorndike (1911) a Skinner (1953). Desse período, foram demonstradas as primeiras tentativas de formular as leis comportamentais atualmente conhecidas: os princípios de reforço (positivo e negativo) e de punição (positiva e negativa). Foram também relatadas e discutidas, brevemente, algumas divergências terminológicas e conceituais atuais, na área do controle aversivo. As divergências referem-se a cinco temas: uso da expressão "reforçador negativo"; distinção entre contingências de reforço positivo e negativo; diferentes posições teóricas a respeito da punição; conceito popular e científico de punição e, exclusão do hedonismo. Os resultados permitem ilustrar importantes debates atuais na área do controle aversivo e demonstrar um pouco do esforço e do empenho que a construção de uma ciência demanda, seja na construção de uma linguagem técnica, seja na construção teórico-conceitual.(AU)

This essay is an attempt to present some important historical aspects on the terminological and conceptual construction of the aversive control. Some topics of the period from Thorndike (1911) to Skinner (1953) were described showing the first attempts to formulate the behavioral laws currently known: the reinforcement and punishment principles (both positive and negative). Some current conceptual and terminological divergences about the aversive control field were also briefly reported and discussed. These divergences refer to five themes: use of the expression "negative reinforcer"; distinction between the positive and the negative reinforcement contingencies; different theoretical approaches of punishment; popular and scientific concepts of punishment and, exclusion of hedonism. The results present important current debates in the aversive control field and show partially the efforts and dedication demanded for the development of a science, be it related to its technical language, or to its theoretical-conceptual construction.(AU)