Domingos Alves

ERROR THRESHOLD IN FINITE POPULATIONS

A simple analytical framework to study the molecular quasispecies evolution of finite populations is proposed, in which the population is assumed to be a random combination of the constiyuent molecules in each generation,i.e., linkage disequilibrium at the population level is neglected. In particular, for the single-sharp-peak replication landscape we investigate the dependence of the error threshold on the population size and find that the replication accuracy at threshold increases linearly with the reciprocal of the population size for sufficiently large populations. Furthermore, in the deterministic limit our formulation yields the exact steady-state of the quasispecies model, indicating then the population composition is a random combination of the molecules.

Incidência do pênfigo vulgar ultrapassa a do pênfigo foliáceo em região endêmica para pênfigo foliáceo: análise de série histórica de 21 anos

FUNDAMENTO: Ha dois tipos principais de penfigo: penfigo vulgar e penfigo foliaceo. Nos ultimos anos, mudancas clinicas e epidemiologicas relacionadas aos penfigos tem sido observadas. OBJETIVOS: Teve-se por objetivo analisar uma serie historica de 21 anos de casos de penfigo vulgar e penfigo foliaceo no nordeste do estado de Sao Paulo, area endemica para o penfigo foliaceo. METODOS: Neste estudo descritivo, foram analisados os dados relacionados a incidencia anual e a idade de inicio do quadro clinico compativel com penfigo vulgar ou penfigo foliaceo, no periodo de 1988 a 2008, comparando-se ambas as formas de penfigo. RESULTADOS: O conjunto dos resultados abrange um periodo de 21 anos, com 103 casos de penfigo vulgar e 163 casos de penfigo foliaceo. A comparacao das linhas de tendencia em relacao a incidencia mostrou ser esta decrescente para o penfigo foliaceo em comparacao aquela de crescimento para o penfigo vulgar. Houve variacao ampla nas faixas de idade, com persistencia da faixa minima de 10 a 20 anos para o penfigo foliaceo (media de idade de 32,1 anos), e clara tendencia de diminuicao da idade minima para o penfigo vulgar (media de idade de 41,5 anos), principalmente a partir da metade da primeira decada do periodo total analisado. CONCLUSOES: A incidencia do penfigo vulgar ultrapassa aquela do penfigo foliaceo a partir de 1998, permanecendo assim ate os dias de hoje. Esta serie historica de 21 anos vem consubstanciar a modificacao da epidemiologia dos penfigos no Brasil, suscitando novas hipoteses para a sua etiopatogenese.

Population genetics approach to the quasispecies model.

A population genetics formulation of Eigen’s molecular quasispecies model [Naturwissenchaften 58, 465 (1971)] is proposed and several simple replication landscapes are investigated analytically. Our results show a remarkable similarity to those obtained with the original kinetics formulation of the quasispecies model. However, due to the simplicity of our approach, the space of the parameters that define the model can be thoroughly explored. In particular, for the single-sharppeak landscape our analysis yields some interesting predictions such as the existence of a maximum peak height and a minimum molecule length for the onset of the error threshold transition.

The development of a Simplified, Effective, Labour Monitoring-to-Action (SELMA) tool for Better Outcomes in Labour Difficulty (BOLD): study protocol

BackgroundThe partograph is currently the main tool available to support decision-making of health professionals during labour. However, the rate of appropriate use of the partograph is disappointingly low. Apart from limitations that are associated with partograph use, evidence of positive impact on labour-related health outcomes is lacking. The main goal of this study is to develop a Simplified, Effective, Labour Monitoring-to-Action (SELMA) tool. The primary objectives are: to identify the essential elements of intrapartum monitoring that trigger the decision to use interventions aimed at preventing poor labour outcomes; to develop a simplified, monitoring-to-action algorithm for labour management; and to compare the diagnostic performance of SELMA and partograph algorithms as tools to identify women who are likely to develop poor labour-related outcomes.Methods/DesignA prospective cohort study will be conducted in eight health facilities in Nigeria and Uganda (four facilities from each country). All women admitted for vaginal birth will comprise the study population (estimated sample size: 7,812 women). Data will be collected on maternal characteristics on admission, labour events and pregnancy outcomes by trained research assistants at the participating health facilities. Prediction models will be developed to identify women at risk of intrapartum-related perinatal death or morbidity (primary outcomes) throughout the course of labour. These predictions models will be used to assemble a decision-support tool that will be able to suggest the best course of action to avert adverse outcomes during the course of labour. To develop this set of prediction models, we will use up-to-date techniques of prognostic research, including identification of important predictors, assigning of relative weights to each predictor, estimation of the predictive performance of the model through calibration and discrimination, and determination of its potential for application using internal validation techniques.DiscussionThis research offers an opportunity to revisit the theoretical basis of the partograph. It is envisioned that the final product would help providers overcome the challenging tasks of promptly interpreting complex labour information and deriving appropriate clinical actions, and thus increase efficiency of the care process, enhance providers’ competence and ultimately improve labour outcomes.Please see related articles ‘http://dx.doi.org/10.1186/s12978-015-0027-6’ and ‘http://dx.doi.org/10.1186/s12978-015-0028-5’.

Error threshold in the evolution of diploid organisms

The effects of error propagation in the reproduction of diploid organisms are studied within the population genetics framework of the quasispecies model. The dependence of the error threshold on the dominance parameter is fully investigated. In particular, it is shown that dominance can protect the wild-type alleles from the error catastrophe. The analysis is restricted to a diploid analogue of the single-peaked fitness landscape.

A web-based information system for a regional public mental healthcare service network in Brazil

BackgroundRegional networking between services that provide mental health care in Brazil’s decentralized public health system is challenging, partly due to the simultaneous existence of services managed by municipal and state authorities and a lack of efficient and transparent mechanisms for continuous and updated communication between them. Since 2011, the Ribeirao Preto Medical School and the XIII Regional Health Department of the Sao Paulo state, Brazil, have been developing and implementing a web-based information system to facilitate an integrated care throughout a public regional mental health care network.Case presentationAfter a profound on-site analysis, the structure of the network was identified and a web-based information system for psychiatric admissions and discharges was developed and implemented using a socio-technical approach. An information technology team liaised with mental health professionals, health-service managers, municipal and state health secretariats and judicial authorities. Primary care, specialized community services, general emergency and psychiatric wards services, that comprise the regional mental healthcare network, were identified and the system flow was delineated. The web-based system overcame the fragmentation of the healthcare system and addressed service specific needs, enabling: detailed patient information sharing; active coordination of the processes of psychiatric admissions and discharges; real-time monitoring; the patients’ status reports; the evaluation of the performance of each service and the whole network. During a 2-year period of operation, it registered 137 services, 480 health care professionals and 4271 patients, with a mean number of 2835 accesses per month. To date the system is successfully operating and further expanding.ConclusionWe have successfully developed and implemented an acceptable, useful and transparent web-based information system for a regional mental healthcare service network in a medium-income country with a decentralized public health system. Systematic collaboration between an information technology team and a wide range of stakeholders is essential for the system development and implementation.

Progression of the first stage of spontaneous labour : a prospective cohort study in two sub-Saharan African countries

Background Escalation in the global rates of labour interventions, particularly cesarean section and oxytocin augmentation, has renewed interest in a better understanding of natural labour progression. Methodological advancements in statistical and computational techniques addressing the limitations of pioneer studies have led to novel findings and triggered a re-evaluation of current labour practices. As part of the World Health Organizations Better Outcomes in Labour Difficulty (BOLD) project, which aimed to develop a new labour monitoring-to-action tool, we examined the patterns of labour progression as depicted by cervical dilatation over time in a cohort of women in Nigeria and Uganda who gave birth vaginally following a spontaneous labour onset. Methods and findings This was a prospective, multicentre, cohort study of 5,606 women with singleton, vertex, term gestation who presented at ≤ 6 cm of cervical dilatation following a spontaneous labour onset that resulted in a vaginal birth with no adverse birth outcomes in 13 hospitals across Nigeria and Uganda. We independently applied survival analysis and multistate Markov models to estimate the duration of labour centimetre by centimetre until 10 cm and the cumulative duration of labour from the cervical dilatation at admission through 10 cm. Multistate Markov and nonlinear mixed models were separately used to construct average labour curves. All analyses were conducted according to three parity groups: parity = 0 (n = 2,166), parity = 1 (n = 1,488), and parity = 2+ (n = 1,952). We performed sensitivity analyses to assess the impact of oxytocin augmentation on labour progression by re-examining the progression patterns after excluding women with augmented labours. Labour was augmented with oxytocin in 40% of nulliparous and 28% of multiparous women. The median time to advance by 1 cm exceeded 1 hour until 5 cm was reached in both nulliparous and multiparous women. Based on a 95th percentile threshold, nulliparous women may take up to 7 hours to progress from 4 to 5 cm and over 3 hours to progress from 5 to 6 cm. Median cumulative duration of labour indicates that nulliparous women admitted at 4 cm, 5 cm, and 6 cm reached 10 cm within an expected time frame if the dilatation rate was ≥ 1 cm/hour, but their corresponding 95th percentiles show that labour could last up to 14, 11, and 9 hours, respectively. Substantial differences exist between actual plots of labour progression of individual women and the ‘average labour curves’ derived from study population-level data. Exclusion of women with augmented labours from the study population resulted in slightly faster labour progression patterns. Conclusions Cervical dilatation during labour in the slowest-yet-normal women can progress more slowly than the widely accepted benchmark of 1 cm/hour, irrespective of parity. Interventions to expedite labour to conform to a cervical dilatation threshold of 1 cm/hour may be inappropriate, especially when applied before 5 cm in nulliparous and multiparous women. Averaged labour curves may not truly reflect the variability associated with labour progression, and their use for decision-making in labour management should be de-emphasized.

Application of the Intelligent Techniques in Transplantation Databases: A Review of Articles Published in 2009 and 2010

The replacement of defective organs with healthy ones is an old problem, but only a few years ago was this issue put into practice. Improvements in the whole transplantation process have been increasingly important in clinical practice. In this context are clinical decision support systems (CDSSs), which have reflected a significant amount of work to use mathematical and intelligent techniques. The aim of this article was to present consideration of intelligent techniques used in recent years (2009 and 2010) to analyze organ transplant databases. To this end, we performed a search of the PubMed and Institute for Scientific Information (ISI) Web of Knowledge databases to find articles published in 2009 and 2010 about intelligent techniques applied to transplantation databases. Among 69 retrieved articles, we chose according to inclusion and exclusion criteria. The main techniques were: Artificial Neural Networks (ANN), Logistic Regression (LR), Decision Trees (DT), Markov Models (MM), and Bayesian Networks (BN). Most articles used ANN. Some publications described comparisons between techniques or the use of various techniques together. The use of intelligent techniques to extract knowledge from databases of healthcare is increasingly common. Although authors preferred to use ANN, statistical techniques were equally effective for this enterprise.

The effectiveness of a rotavirus vaccine in preventing hospitalizations and deaths presumably due to acute infectious diarrhea in Brazilian children: a quasi-experimental study

INTRODUCTION Rotavirus is the main etiologic agent of acute infectious diarrhea in children worldwide. Considering that a rotavirus vaccine (G1P8, strain RIX4414) was added to the Brazilian vaccination schedule in 2006, we aimed to study its effectiveness and safety regarding intestinal intussusception. METHODS A quasi-experimental trial was performed in which the primary outcome was the number of hospitalizations that were presumably due to acute infectious diarrhea per 100,000 children at risk (0-4 years old). The secondary outcomes included mortality due to acute infectious diarrhea and the intestinal intussusception rates in children in the same age range. We analyzed three scenarios: Health Division XIII of the State of São Paulo (DRS XIII) from 2002 to 2008, the State of São Paulo, and Brazil from 2002 to 2012. RESULTS The averages of the hospitalization rates for 100,000 children in the pre- and post-vaccination periods were 1,413 and 959, respectively, for DRS XIII (RR=0.67), 312 and 249, respectively, for the State of São Paulo (RR=0.79), and 718 and 576, respectively, for Brazil (RR=0.8). The mortality rate per 100,000 children in the pre- and post-vaccination periods was 2.0 and 1.3, respectively, for DRS XIII (RR=0.66), 5.5 and 2.5, respectively, for the State of São Paulo (RR=0.47), and 15.0 and 8.0, respectively, for Brazil (RR=0.53). The average annual rates of intussusception for 100,000 children in DRS XIII were 28.0 and 22.0 (RR=0.77) in the pre- and post-vaccination periods, respectively. CONCLUSIONS A monovalent rotavirus vaccine was demonstrated to be effective in preventing the hospitalizations and deaths of children that were presumably due to acute infectious diarrhea, without increasing the risk of intestinal intussusception.

Small-World Effect in Epidemics Using Cellular Automata

The spread of an infectious disease in a population involves interactions leading to an epidemic outbreak through a network of contacts. Extending on Watts and Strogatz (1998) who showed that short-distance connections create a small-world effect, a model combining short- and long-distance probabilistic and regularly updated contacts helps considering spatial heterogeneity. The method is based on cellular automata. The presence of long-distance connections accelerates the small-world effect, as if the world shrank in proportion of their total number.