A bootstrap-aggregated hybrid semi-parametric modeling framework for bioprocess development.

Hybrid semi-parametric modeling, combining mechanistic and machine-learning methods, has proven to be a powerful method for process development. This paper proposes bootstrap aggregation to increase the predictive power of hybrid semi-parametric models when the process data are obtained by statistical design of experiments. A fed-batch Escherichia coli optimization problem is addressed, in which three factors (biomass growth setpoint, temperature, and biomass concentration at induction) were designed statistically to identify optimal cell growth and recombinant protein expression conditions. Synthetic data sets were generated applying three distinct design methods, namely, Box-Behnken, central composite, and Doehlert design. Bootstrap-aggregated hybrid models were developed for the three designs and compared against the respective non-aggregated versions. It is shown that bootstrap aggregation significantly decreases the prediction mean squared error of new batch experiments for all three designs. The number of (best) models to aggregate is a key calibration parameter that needs to be fine-tuned in each problem. The Doehlert design was slightly better than the other designs in the identification of the process optimum. Finally, the availability of several predictions allowed computing error bounds for the different parts of the model, which provides an additional insight into the variation of predictions within the model components.

In Vivo Measurement of Root Canal Wall Temperature at Different Stages Prior to Fiber Post Cementation.

OBJECTIVE: This study measured the in vivo temperature of prepared root canal walls during various stages of treatment prior to endodontic postcementation. MATERIALS AND METHODS: One tooth each from five patients requiring endodontic treatment received conventional gutta-percha obturation. The coronal 4 mm of gutta-percha was removed by drilling and the canal wall temperature was measured. A sterile, saline rinse was applied, and another temperature value was recorded. Paper points were placed, and the wall temperature was recorded. A standardized period of 1.5 minute passed, simulating time needed to mix and place the resin cement and post (no resin was placed), after which the final wall temperature was obtained. The tooth was temporized and scheduled for prosthetic reconstruction. A one-way repeated measure analysis of variance (with Tukey's post hoc test) was performed among mean temperature values for each treatment stage (preset α 0.05). RESULTS: Significant temperature differences were found among the treatment stages. Canal space drilling yielded the highest temperature (35.5 ± 0.8°C), while the lowest was obtained after saline rinsing (34.0 ± 0.9°C). The temperature of prepared root canal wall prior to postplacement (34.9 ± 1.2°C) and following paper point drying (34.8 ± 1.1°C) presented intermediate results, with no statistical difference between them. CONCLUSIONS: This study suggested that root canal wall temperature varied during various stages of preparation prior to endodontic post.

Modeling of the burst release from PLGA micro- and nanoparticles as function of physicochemical parameters and formulation characteristics.

A substantial drug release from poly(lactic-co-glycolic) acid (PLGA) micro- and nanoparticles can occur in the first hours of immersion, which is referred to as burst release. A strong burst release (when not intentional) is to be avoided as it decreases the efficacy of the treatment and could be dangerous to the host. In this work we analyze the total amount of drug released during burst and respective kinetics in relation to formulations characteristics, experimental conditions and drug molecular properties in 154 drug release experiments with 41 different drugs by partial least squares (PLS) and decision tree regression. The model created enables to quantify to which degree the physicochemical parameters control the burst release from PLGA particles. Our analysis shows that the amount of drug released during burst is mostly influenced by the formulation characteristics and the synthesis parameters, whereas the drug release kinetics is also influenced by the molecular properties of the drug. The variables that significantly influence the amount and kinetics of the burst release are discussed in detail and compared with findings from other researchers. The final regression models are shown to predict the release profile of a new drug, opening the possibility to be applied to systematically manipulate the burst release by means of designing an optimized drug delivery system.

A principal components method constrained by elementary flux modes: analysis of flux data sets.

BACKGROUND: Non-negative linear combinations of elementary flux modes (EMs) describe all feasible reaction flux distributions for a given metabolic network under the quasi steady state assumption. However, only a small subset of EMs contribute to the physiological state of a given cell. RESULTS: In this paper, a method is proposed that identifies the subset of EMs that best explain the physiological state captured in reaction flux data, referred to as principal EMs (PEMs), given a pre-specified universe of EM candidates. The method avoids the evaluation of all possible combinations of EMs by using a branch and bound approach which is computationally very efficient. The performance of the method is assessed using simulated and experimental data of Pichia pastoris and experimental fluxome data of Saccharomyces cerevisiae. The proposed method is benchmarked against principal component analysis (PCA), commonly used to study the structure of metabolic flux data sets. CONCLUSIONS: The overall results show that the proposed method is computationally very effective in identifying the subset of PEMs within a large set of EM candidates (cases with ~100 and ~1000 EMs were studied). In contrast to the principal components in PCA, the identified PEMs have a biological meaning enabling identification of the key active pathways in a cell as well as the conditions under which the pathways are activated. This method clearly outperforms PCA in the interpretability of flux data providing additional insights into the underlying regulatory mechanisms.

APOLLO I: Anticoagulation control in atrial fibrillation.

INTRODUCTION AND AIMS: Anticoagulation control as assessed by time in therapeutic range (TTR) correlates positively with the safety and efficacy of thromboprophylaxis in atrial fibrillation. We set out to assess TTR in our unit and to investigate determinants of better control. METHODS: This was a case series study of atrial fibrillation patients anticoagulated with warfarin or acenocoumarol at the Family Health Unit of Fânzeres. Sociodemographic and clinical data were collected and TTR was calculated by the Rosendaal method, based on international normalized ratio tests performed in external laboratories in the preceding six months. SPSS 21.0 was used for the statistical analysis, with descriptive statistics, Spearman's correlation, and the Mann-Whitney U and Kruskal-Wallis tests. RESULTS: Of the 106 eligible patients, 70% participated in the study. Median TTR was 65.3% (P25=48.3%, P75=86.8%). We found a positive association between this variable and duration of atrial fibrillation (ρ=0.477, p<0.001, r(2)=0.116) and with duration of anticoagulation (ρ=0.5, p<0.001, r(2)=0.087). No association was found with age, gender, educational level or existence of a caregiver (p>0.05). CONCLUSIONS: Median TTR in our unit is similar to that in southern European countries and close to the good control threshold (70%) proposed by the European Society of Cardiology. The duration of atrial fibrillation and of anticoagulation explains only a small part of the measure's variability. Other determinants of anticoagulation control must be investigated in future studies and comparative studies should be carried out in family health units monitoring anticoagulation on the premises.

1-Year clinical study of indirect resin composite restorations luted with a self-adhesive resin cement: effect of enamel etching.

In vitro studies have recommended enamel-etching before luting indirect restorations with self-adhesive resin cement. However, there is no scientific proof that this procedure has any clinical relevance. Thus, the aim of this study was to evaluate the effect of enamel-etching on the marginal quality of indirect composite resin restorations (inlay/onlay) using the self-adhesive cement RelyX Unicem clicker. Forty-two posterior teeth were selected from 25 patients that presented one or two teeth with large restorations in need of replacement. All teeth were prepared by the same operator and impressed with polyvinylsiloxane material. The composite resin restorations were built over plaster casts using the incremental technique with a LED device for light-curing the increments. The inlays/onlays were cemented according to one of the following protocols: 1. Etched group (ETR) - selective enamel phosphoric-acid etching + RelyX Unicem clicker; 2. Non-etched group (NER) - RelyX Unicem clicker alone. Each surface was light-cured for 60 s. Recalls occurred after 1 week (baseline), 6 and 12 months when the teeth were evaluated according to previously established scores (modified USPHS criteria). The clinical analysis showed little or no visible changes in the marginal quality after 1 year, even though a probe could detect all the restorations margins. Statistical analysis (Fisher's exact test, p<0.05) detected no differences between the groups after 12 months. No restorations failed and no secondary caries were found. Enamel acid etching had no clinical relevance on the marginal quality of indirect composite resin restorations luted with RelyX Unicem clicker after 1 year of follow up.

1-Year clinical study of indirect resin composite restorations luted with a self-adhesive resin cement: effect of enamel etching

In vitro studies have recommended enamel-etching before luting indirect restorations with self-adhesive resin cement. However, there is no scientific proof that this procedure has any clinical relevance. Thus, the aim of this study was to evaluate the effect of enamel-etching on the marginal quality of indirect composite resin restorations (inlay/onlay) using the self-adhesive cement RelyX Unicem clicker. Forty-two posterior teeth were selected from 25 patients that presented one or two teeth with large restorations in need of replacement. All teeth were prepared by the same operator and impressed with polyvinylsiloxane material. The composite resin restorations were built over plaster casts using the incremental technique with a LED device for light-curing the increments. The inlays/onlays were cemented according to one of the following protocols: 1. Etched group (ETR) - selective enamel phosphoric-acid etching + RelyX Unicem clicker; 2. Non-etched group (NER) - RelyX Unicem clicker alone. Each surface was light-cured for 60 s. Recalls occurred after 1 week (baseline), 6 and 12 months when the teeth were evaluated according to previously established scores (modified USPHS criteria). The clinical analysis showed little or no visible changes in the marginal quality after 1 year, even though a probe could detect all the restorations margins. Statistical analysis (Fisher’s exact test, p<0.05) detected no differences between the groups after 12 months. No restorations failed and no secondary caries were found. Enamel acid etching had no clinical relevance on the marginal quality of indirect composite resin restorations luted with RelyX Unicem clicker after 1 year of follow up.

Estudos in vitro têm recomendado condicionamento ácido do esmalte antes da cimentação de restaurações indiretas com cimento resinoso autoadesivo. Entretanto, não há nenhuma prova científica de que este procedimento tenha relevância clínica. Assim, o objetivo deste estudo foi avaliar o efeito do condicionamento ácido do esmalte na qualidade marginal de restaurações indiretas de resina composta (inlay/onlay) usando o cimento autoadesivo RelyX Unicem clicker. Quarenta e dois dentes posteriores foram selecionados de 25 pacientes com 1 ou 2 restaurações amplas com necessidade de substituição. Todos os dentes foram preparados pelo mesmo operador e impressos com material à base de polivilsiloxano. As restaurações de resina composta foram construídas sobre troquel de gesso usando a técnica de colocação em camadas e polimerizadas usando aparelho de luz emitida por diodo (LED). Osinlays/onlays foram cimentados de acordo com um dos protocolos: 1. Grupo condicionado (ETR)- condicionamento seletivo do esmalte com ácido fosfórico + cimentação com RelyX Unicem clicker; 2. Grupo não condicionado (NER)- cimentação com RelyX Unicem clicker somente. Cada superfície foi fotoativada por 60 s. Os retornos para acompanhamento foram feitos após 1 semana (baseline), 6 e 12 meses onde os dentes foram avaliados de acordo com critérios previamente estabelecidos (USPHS Modificado). A análise clínica mostrou pouca ou nenhuma alteração visível na qualidade marginal após 1 ano, porém uma sonda clínica pode detectar todas as margens restauradoras. A análise estatística (Teste exato de Fisher, p<0,05) não detectou diferença entre os grupos após 12 meses. Nenhuma restauração falhou e nenhuma cárie secundária foi encontrada. O condicionamento ácido do esmalte não teve relevância clínica na qualidade marginal de restaurações indiretas de resina composta cimentadas com RelyX Unicem clicker após 1 ano de acompanhamento.

Planejamento como instrumento de sucesso no restabelecimento do sorriso / Planning as a success tool for recovery of the smile

Dentes anteriores manchados e desgastados podem comprometer a beleza de um sorriso. Independentemente da forma escolhida para restabelecer as características desejadas, o conhecimento da anatomia e proporção dental é fundamental para o planejamento do caso. Além disso, é importante que a projeção do resultado possa ser provada e confirmada antecipadamente, estimulando colaboração e confiança do paciente e segurança na execução, para o profissional. Este artigo relata o planejamento e a previsibilidade de um caso clínico de restabelecimento do sorriso, em que se utiliza resina composta nanoparticulada...

Stained, worn anterior teeth may jeopardize the beauty of a smile. Knowledge about anatomy and tooth proportions is essential for treatment planning, regardless of the technique chosen to restore the desired esthetic characteristics. It is also important that the results of the planning can be checked and approved in advance. This procedure not only encourages the patient to authorize the treatment but also allows for a greater confidence on the treatment outcome. This paper reports the planning and predictabilty of smile recovery using a nanofilled composite resin...

Recuperação da cor em dente escurecido: relato de caso clínico / Shade recovery of anterior discolored teeth: a clinical report

Dentes anteriores escurecidos comprometem a estética do sorriso. Etiologicamente, a alteração de cor, de um ou mais dentes isolados nos arcos dentários está relacionada a trauma mecânico e/ou tratamento endodôntico inadequado. A cor é uma das características mais marcantes dos dentes e pode ser interpretada por meio de três parâmetros: matiz, croma e valor. A visão humana possui grande número de células sensíveis à luminosidade. Assim, além da mudança cromática, a alteração mais perceptível nos dentes escurecidos é a perda de valor. Este artigo mostra dois casos clínicos com resoluções diferentes para recuperação da cor de dentes escurecidos no setor ântero-superior: clareamento e faceta direta de resina composta utilizando cores opacas e de alto valor.

Anterior discolored teeth jeopardize smile esthetics. Etiologically, discoloration of one ormore isolated teeth in dental arches is related to mechanical trauma and/or inadequate en¬dodontic treatment. Color is a unique tooth characteristic, and can be interpreted by three parameters: hue, chroma and value. The human eye has great quantity of cells that are sensitive to light intensity. Hence, although chroma changes, lower values tend to be most frequently noticed. This paper describes two clinical cases with different approaches for the esthetic recovery of upper anterior discolored teeth: bleaching and confection of direct composite resin veneers with opaque and high value shades.