Maximizing mRNA vaccine production with Bayesian optimization

Messenger RNA (mRNA) vaccines are a new alternative to conventional vaccines with a prominent role in infectious disease control. These vaccines are produced in in vitro transcription (IVT) reactions, catalyzed by RNA polymerase in cascade reactions. To ensure an efficient and cost-effective manufacturing process, essential for a large-scale production and effective vaccine supply chain, the IVT reaction needs to be optimized. IVT is a complex reaction that contains a large number of variables that can affect its outcome. Traditional optimization methods rely on classic Design of Experiments methods, which are time-consuming and can present human bias or based on simplified assumptions. In this contribution, we propose the use of Machine Learning approaches to perform a data-driven optimization of an mRNA IVT reaction. A Bayesian optimization method and model interpretability techniques were used to automate experiment design, providing a feedback loop. IVT reaction conditions were found under 60 optimization runs that produced 12 g · L−1 in solely 2 h. The results obtained outperform published industry standards and data reported in literature in terms of both achievable reaction yield and reduction of production time. Furthermore, this shows the potential of Bayesian optimization as a cost-effective optimization tool within (bio)chemical applications

Inequalities in public water supply fluoridation in Brazil: An ecological study

Background. The literature is scarce on the social and geographic inequalities in the access to and implementation of the fluoridation of public water supplies. This study adds knowledge to the Brazilian experience of the chronic privation of water and wastewater policies, access to potable water and fluoridation in the country. Thus, the aim of this study was to verify possible inequalities in the population's access to fluoridated drinking water in 246 Brazilian municipalities. Methods. The information on the process of water fluoridation in the municipalities and in the macro region in which each municipality is located was obtained from the national epidemiological survey which was concluded in 2003. The data relating to the human development index at municipal level (HDI-M) and access to mains water came from the Brazilian Human Development Atlas, whilst the size of the population was obtained from a governmental source. The Fisher exact test (P < 0.05) was employed to identify significant associations between the explanatory variables and their ability to predict the principal outcomes of interest to this study, namely the presence or absence of the water fluoridation process in the municipalities as well as the length of time during which this measure has been implemented. Linear regression was used to observe the associations between the relevant variables in a multivariate environment. Results. The results clearly showed that there is a relationship between municipalities with larger populations, located in more socio-economically advantaged regions and with better HDI-M, and where fluoridation is both present and has been implemented for a longer period of time (started before 1990). Conclusion. The findings suggest that the aim of treating water with fluoride may not be being adequately achieved, requiring more effective strategies so that access to this measure can be expanded equitably.81Hart, J.T., The inverse care law (1971) Lancet, 1 (7696), pp. 405-12. , 4100731Victora, C.G., Vaughan, J.P., Barros, F.C., Silva, A.C., Tomasi, E., Explaining trends in inequities: Evidence from Brazilian child health studies (2000) Lancet, 356 (9235), pp. 1093-98. , 10.1016/S0140-6736(00)02741-0 11009159Basting, R.T., Pereira, A.C., Meneghim, M.C., Evaluation of dental caries prevalence in students from Piracicaba, SP, Brazil, after 25 years of fluoridation of the public water supply (1997) Rev Odontol Univ São Paulo, 11 (4), pp. 287-92. , 10.1590/S0103-06631997000400010Lawrence, H.P., Sheiham, A., Caries progression in 12 to 16-year-old schoolchildren in fluoridated and fluoride-deficient areas in Brazil (1997) Community Dent Oral Epidemiol, 25 (6), pp. 402-11. , 10.1111/j.1600-0528.1997.tb01730.x 9429812Pereira, A.C., Mialhe, F.L., Bianchini, F.L.C., Prevalence of caries and dental floozies in scholars from cities with different fluoride concentrations in drinking water (2001) Rev Bras Odontol Sade Coletiva, 2 (1), pp. 34-9For Disease Control, C., Prevention, Achievementsin Public Health, 1900-1999: Fluoridation of drinking water to prevent dental caries (1999) Morbidity and Mortality Weekly Report, 48 (41), pp. 933-40For Disease Control, C., Prevention, Ten great public health achievements -United Sates, 1900-1999 (1999) Morbidity and Mortality Weekly Report, 48 (12), pp. 241-3. , 10220250American Health Organization, P., XV Directing Council of the Pan American Health Organization - Resolutions, 1964, , http://www.paho.org/English/GOV/CD/ftcd_15.htm(2003) The World Oral Health Report 2003, , http://www.who.int/oral_health, Geneva: WHOMcDonagh, M.S., Whiting, P.F., Wilson, P.M., Sutton, A.J., Chestnutt, I., Cooper, J., Misso, K., Kleijnen, J., Systematic review of water fluoridation (2000) BMJ, 321 (7265), pp. 855-9. , 11021861 10.1136/bmj.321.7265.855Bratthall, D., Hänsel-Petersson, G., Sundberg, H., Reasons for the caries decline: What do the experts believe? (1996) Eur J Oral Sci, 104 (4 PART 2), pp. 416-22. , 10.1111/j.1600-0722.1996.tb00104.x 8930592Narvai, P.C., Dental caries and fluorine: A twentieth century relation (2000) Cinc Sade Coletiva, 5 (2), pp. 381-92. , 10.1590/S1413-81232000000200011Peres, M.A., Fernandes, L.S., Peres, K.G., Inequality of water fluoridation in Southern Brazil - The inverse equity hypothesis revisited (2004) Soc Sci Med, 58 (6), pp. 1181-9. , 10.1016/S0277-9536(03)00289-2 14723912Peres, M.A., Antunes, J.L.F., Peres, K.G., Is water fluoridation effective in reducing inequalities in dental caries distribution in developing countries? (2006) Sozial und Präventiv Medizin, 51 (5), pp. 1-9Peres, K.G., Bastos, J.R., Mrdo, L., Relationship between severity of dental caries and social and behavioral factors in children (2000) Rev Saude Publica, 34 (4), pp. 402-8. , 10973161Maltz, M., Barbachan Silva, E.B., Relationship between caries, gingivitis and fluorosis and the socioeconomic status among school children (2001) Rev Saude Publica, 35 (2), pp. 170-6. , 11359204Moysés, S.J., Desigualdades em Sade Bucal e Desenvolvimento Humano: Um ensaio em preto, branco e alguns tons de cinza (2001) Rev Bras Odontol Sade Coletiva, 1 (1), pp. 7-17Patussi, M.P., Marcenes, W., Croucher, R., Sheiham, A., Social deprivation, income inequality, social cohesion and dental caries in Brazilian school children (2001) Soc Sci Med, 53 (7), pp. 915-25. , 10.1016/S0277-9536(00)00391-9 11522137Antunes, J.L.F., Frazão, P., Narvai, P.C., Bispo, C.M., Pegoretti, T., Spatial analysis to identify differentials in dental needs by area-based measures (2002) Community Dent Oral Epidemiol, 30 (2), pp. 133-42. , 10.1034/j.1600-0528.2002.300207.x 12000354Peres, M.A., Peres, K.G., Antunes, J.L.F., Junqueira, S.R., Frazão, P., Narvai, P.C., The association between socioeconomic development at the town level and the distribution of dental caries in Brazilian children (2003) Rev Panam Salud Publica, 14 (3), pp. 149-57. , 10.1590/S1020-49892003000800001 14653902Antunes, J.L.F., Narvai, P.C., Nugent, Z.J., Measuring inequalities in the distribution of dental caries (2004) Community Dent Oral Epidemiol, 32 (1), pp. 41-8. , 10.1111/j.1600-0528.2004.00125.x 14961839Antunes, J.L.F., Peres, M.A., De Campos Mello, T.R., Waldman, E.A., Multilevel assessment of determinants of dental caries experience in Brazil (2006) Community Dent Oral Epidemiol, 34 (2), pp. 146-152. , 10.1111/j.1600-0528.2006.00274.x 16515679Narvai, P.C., Frazão, P., Roncalli, A.G., Antunes, J.L.F., Dental caries in Brazil: Decline, polarization, inequality and social exclusion (2006) Rev Panam Salud Publica, 19 (6), pp. 385-93. , 10.1590/S1020-49892006000600004 16968593Projeto, S.B., Brasil, Condiçes de sade bucal da população brasileira 2002-2003. Resultados principais (2004) Brasília-DF: Ministério da Sade, Secretaria de Atenção Sade, Departamento de Atenção Básica, Coordenação Nacional de Sade BucalCarmichael, C.L., Rugg-Gunn, A.J., French, A.D., Cranage, J.D., The effect of fluoridation upon the relationship between caries experience and social class in 5-year-old children in Newcastle and Northumberland in 1987 (1980) Br Dent J, 149 (6), pp. 163-7. , 10.1038/sj.bdj.4804479 6931610Bradnock, G., Marchment, M.D., Anderson, R.J., Social background, fluoridation and caries experience in 5-year-old population in the West Midlands (1984) Br Denl J, 156 (4), pp. 127-31. , 10.1038/sj.bdj.4805287 6584119Jones, C.M., Taylor, G.O., Whittle, J.G., Evans, D., Trotter, D.P., Water fluoridation, tooth decay in 5 years olds, and social deprivation measured by the Jarman score: Analysis of data from British dental surveys (1997) BMJ, 315 (7107), pp. 514-17. , 9329305Riley, J.C., Lennon, M.A., Ellwood, R.P., The effect of water fluoridation and social inequalities on dental caries in 5-year-old children (1999) Int Dent J, 28 (2), pp. 300-5. , 10342695Congresso Nacional, Brasil., Lei Federal no. de 19/09/1990 (1990) Diário Oficial da União 20 Set, p. 18055Morgenstern, H., Ecological studies (1998) Modern Epidemiology, pp. 459-80. , Baltimore: Lippincot Williamns & Wilkins Rothman K, Greenland S(2000) Informaçes de Sade: População Residente, , http://w3.datasus.gov.br/datasus/datasus.php?area= 359A1B379C6D0E0F359G23HIJd6L26M0N&VInclude=./site/infsaude.php, Departamento de Informática do Sistema nico de Sade (DATASUS)(2003) Atlas Do Desenvolvimento Humano No Brasil, Versão 1.0.0, , Programa das Naçes Unidas para o Desenvolvimento Brasília: PNUDLallo, R., Myburgh, N.G., Hobdell, M.H., Dental caries, socio-economic development and national oral health profiles (1999) Int Dent J, 49, pp. 196-202. , 10858754Baldani, M.H., Narvai, P.C., Antunes, J.L.F., Cárie dentária e condiçes scio-econômicas no Estado do Paraná, Brasil, 1996 (2002) Cad Sade Pblica, 18 (3), pp. 755-63. , 10.1590/S0102-311X2002000300024Qizilbash, M., On the Measurement of Human Development (2002) UNDP, , http://hdr.undp.org/docs/training/oxford/presentations/ Qizilbash_HDIcritique.pdfBurt, B.A., Fluoridation and social equity (2002) J Public Health Dent, 62 (4), pp. 195-200. , 10.1111/j.1752-7325.2002.tb03445.x 12474623For Disease Control, C., Prevention, Recommendation focusing fluoride to prevent and control dental caries in the United States (2001) Morbidity and Mortality Weekly Report, 50 (14), pp. 1-42Griffin, S.O., Jones, K., Tomar, S.L., An economic evaluation of community water fluoridation (2001) J Public Health Dent, 61 (2), pp. 78-86. , 10.1111/j.1752-7325.2001.tb03370.x 11474918Bleicher, L., Frota, F.H.S., Fluoretação da água: Uma questão de política pblica - O caso do Estado do Ceará (2006) Cin Sade Coletiva, 11 (1), pp. 71-8Frias, A.C., Narvai, P.C., Arajo, M.E., Zilbovicius, C., Antunes, J.L.F., Custo da fluoretação das águas de abastecimento pblico, estudo de caso -Município de São Paulo, Brasil, período de 1985-2003 (2006) Cad Sade Pblica, 22 (6), pp. 1237-46. , 10.1590/S0102-311X2006000600013Congresso Nacional, Brasil., (1974) Lei Federal No. 6.050, 3, p. 107. , Brasília: Departamento de Imprensa Nacional Atos do Poder Legislativo. Leis de Abril a JunhoDuarte, C.M.R., Eqüidade na legislação: Um princípio do sistema de sade brasileiro? (2000) Cin Sade Coletiva, 5 (2), pp. 443-63Whitehead, M., The concepts and principles of equity and health (1992) Int J Health Serv, 22 (3), pp. 429-45. , 10.2190/986L-LHQ6-2VTE-YRRN 164450

Perfis epidemiologicos de saude bucal no Brasil e os modelos de vigilancia

Abstract published in English and Portuguese English title: Oral health epidemiology and surveillance models in BrazilNational surveys are important tools for public health surveillance and thus key elements in monitoring health conditions and system performance. In the field of oral health, such surveys began with the oral health survey in 1986 and later in 1996 and with the SBBrasil Project in 2003. The 2010 edition of SBBrasil is the principal oral health surveillance strategy for the production of primary data. In order to contribute to this discussion, this article proposes: (a) to present and discuss the Brazilian experience with nationwide oral health surveys and (b) to discuss the use of data in health surveillance models. One can conclude that oral health surveys in Brazil have great possibilities as a tool for health services and academia. Such surveys have shown evident potential for verifying trends in the oral health profile, as well as for producing valid indicators for use in health services. = Inquéritos nacionais são importantes ferramentas no campo da vigilância em saúde e elementos fundamentais no monitoramento das condições de saúde e do desempenho do sistema. Na saúde bucal, tais inquéritos surgem a partir do primeiro levantamento em saúde bucal de 1986 e, posteriormente, o de 1996 e o Projeto SBBrasil 2003. A edição 2010 do SBBrasil se coloca como a principal estratégia de vigilância em saúde bucal no que diz respeito à produção de dados primários. No sentido de contribuir com essa discussão, este artigo se propôs a: (a) apresentar e discutir a experiência brasileira em inquéritos nacionais de saúde bucal; (b) discutir a utilização dos dados em modelos de vigilância em saúde. Pode-se concluir que os inquéritos de saúde bucal no Brasil têm grandes possibilidades de se estabelecer como ferramenta para os serviços e para a academia. Ficou evidente sua potencialidade em verificar tendências no perfil de saúde bucal, bem como em produzir indicadores válidos para uso em serviços.Angelo Giuseppe Roncalli, Maria Ilma de Souza Côrtes, Karen Glazer Pere

Poverty, social exclusion and dental caries of 12-year-old children: a cross-sectional study in Lima, Peru

Background: Socioeconomic differences in oral health have been reported in many countries. Poverty and social exclusion are two commonly used indicators of socioeconomic position in Latin America. The aim of this study was to explore the associations of poverty and social exclusion with dental caries experience in 12-year-old children. Methods: Ninety families, with a child aged 12 years, were selected from 11 underserved communities in Lima (Peru), using a two-stage cluster sampling. Head of households were interviewed with regard to indicators of poverty and social exclusion and their children were clinically examined for dental caries. The associations of poverty and social exclusion with dental caries prevalence were tested in binary logistic regression models. Results: Among children in the sample, 84.5% lived in poor households and 30.0% in socially excluded families. Out of all the children, 83.3% had dental caries. Poverty and social exclusion were significantly associated with dental caries in the unadjusted models (p = 0.013 and 0.047 respectively). In the adjusted model, poverty remained significantly related to dental caries (p = 0.008), but the association between social exclusion and dental caries was no longer significant (p = 0.077). Children living in poor households were 2.25 times more likely to have dental caries (95% confidence interval: 1.24; 4.09), compared to those living in non-poor households. Conclusion: There was support for an association between poverty and dental caries, but not for an association between social exclusion and dental caries in these children. Some potential explanations for these findings are discussed