AB2CO risk score for in-hospital mortality of COVID-19 patients admitted to intensive care units.

PURPOSE: To develop a mortality risk score for COVID-19 patients admitted to intensive care units (ICU), and to compare it with other existing scores. MATERIALS AND METHODS: This retrospective observational study included consecutive adult patients with laboratory-confirmed COVID-19 admitted to ICUs of 18 hospitals from nine Brazilian cities, from September 2021 to July 2022. Potential predictors were selected based on the literature review. Generalized Additive Models were used to examine outcomes and predictors. LASSO regression was used to derive the mortality score. RESULTS: From 558 patients, median age was 69 years (IQR 58-78), 56.3 % were men, 19.7 % required mechanical ventilation (MV), and 44.8 % died. The final model comprised six variables: age, pO2/FiO2, respiratory function (respiratory rate or if in MV), chronic obstructive pulmonary disease, and obesity. The AB2CO had an AUROC of 0.781 (95 % CI 0.744 to 0.819), good overall performance (Brier score = 0.191) and an excellent calibration (slope = 1.063, intercept = 0.015, p-value = 0.834). The model was compared with other scores and displayed better discrimination ability than the majority of them. CONCLUSIONS: The AB2CO score is a fast and easy tool to be used upon ICU admission.

Preoperative Locoregional Therapy May Relate with Stemness and Distinct Transitions Between Epithelial and Mesenchymal States in Hepatocellular Carcinoma.

Background/Objectives: Locoregional therapy (LRT) might impel hepatocellular carcinoma (HCC) to exhibit different phenotypes by modulating tumoral cell adaptation. HCCs presurgically treated with LRT were studied, focusing on stemness and mesenchymal features. Methods: Clinicopathological and immunohistochemical data (Ki67, p53, EpCAM, CK19, CK7, ASMA and vimentin expression) were considered in 89 HCC nodules (30 treated with LRT; 59 non-treated), comprising 46 liver transplanted/surgically resected patients. Results: In LRT group, well and poorly differentiated tumors without fibrous encapsulation were predominant (P < 0.05) and peritumoral necroinflammation severity tended to be greater. Peritumoral Ki67 expression was higher (P < 0.05) and p53, EpCAM, CK19 and CK7 peritumoral expression was relevant after LRT, where ablated carcinomas displayed higher peritumoral CK19 expression (P < 0.05). Tumoral ASMA and vimentin expression was higher in non-LRT group (P < 0.05). In LRT group, an exclusive association between progenitor/cholangiocytic cell and mesenchymal markers expressed by tumoral cells was observed (P < 0.05): EpCAM tumoral expression associated with vimentin stromal expression; tumoral CK19 expression associated with stromal ASMA expression; tumoral CK7 expression associated with tumoral vimentin expression. Conclusion: Peritumoral cellular proliferation and expression of progenitor/cholangiocytic cell markers seem to be more frequent after LRT, with a distinctive epithelial-mesenchymal interplay and plasticity in peritumoral and tumoral compartments.

Hepatocellular carcinoma: tumor heterogeneity and recurrence after preoperative locoregional therapy.

How locoregional therapy (LRT) may change tumor compositional and functional heterogeneity, consequently contributing to treatment resistance and tumor recurrence remains largely unknown. A series of hepatocellular carcinomas (HCCs) treated with preoperative locoregional therapy (LRT) that relapsed after surgery was studied. Thirty HCCs comprising 15 patients treated with LRT prior to liver transplantation (n = 14)/surgical resection (n = 1) were studied. Five patients undergoing pre-transplant LRT, comprising 11 HCCs, presented tumor recurrence (median recurrence time = 10 months). Clinicopathological data and immunoexpression of proliferation markers (Ki67, p53), cholangiocytic/hepatic progenitor cell (HPC) markers (EpCAM)/BerEp4, CK19, CK7) and mesenchymal markers (ASMA, vimentin) were evaluated in tumoral epithelial/stromal cells and in peritumoral parenchyma. Higher grading of tumor differentiation, microvascular invasion and tumoral cell p53 expression significantly associated with recurrence (p < 0.05). Piecemeal necrosis features were more frequent in tumors that recurred (p < 0,05). Tumoral and peritumoral Ki67 expression and EpCAM, CK19 and CK7 expression in tumoral cells tended to be higher in treated tumors that recurred. Peritumoral expression of cholangiocytic/HPC markers and tumoral epithelial and stromal cellular expression of mesenchymal markers tended to be higher for tumors without recurrence. Recurrence after transplant with preoperative LRT might be associated with poor HCC differentiation, higher cellular proliferation rate, peritumoral piecemeal necrosis features and cholangiocytic/HPC phenotypes. Understanding HCC progression factors after LRT might be important for optimizing patient selection for treatment, improving surveillance after LRT and to explore synergies between LRT and systemic targeted therapies to prevent recurrence.

Impacts of the antartic ozone hole influence events over southern Brazil in October 2015.

The impact of the Antarctic Ozone Hole Influence over Southern Brazil in October 2015 was analyzed using daily mean data of the Total Column Ozone (TCO), Ultraviolet Index (UVI) and Radiative Cloud Fraction (RCF) from the Ozone Monitoring Instrument satellite instrument. Vertical profiles and fields of ozone content and Potential Vorticity available from the European Centre for Medium-Range Weather Forecast reanalysis, air masses backward trajectories from the HYbrid Single-Particle Lagrangian Integrated Trajectory model and channel 3 water vapor images from the Geostationary Operational Environmental Satellite GOES-13 were also analyzed. The five identified events showed an -7.4±2.3% average TCO reduction, leading to an +16.6±54.6% UVI increase even with a predominance of partly cloudy days. Other impacts were observed in the ozone profiles, where the most significant anomalies occurred from 650 K reaching 1.2 ppmv at the 850 K level. In the ozone fields at 700 K, the presence of a polar origin tongue was observed causing negatives anomalies between -0.2 and 0.4 ppmv in a transient system format forced with eastward-traveling Rossby waves passing through the Southern of Brazil and Uruguay.

A new process analytical technology soft sensor based on electrical tomography for real-time monitoring of multiphase systems.

BACKGROUND: Electrical tomography is widely recognized for its high time resolution and low cost. However, the implementation of electrical tomographic solutions has been hindered by the high computational overhead associated, which causes delays in the analysis, and numerical instability, that results in unclear reconstructed images. Therefore, it has been mostly applied offline, for qualitative tasks and with some delay. Applications requiring fast response times and quantification have been hindered or ruled out. RESULTS: In this article, we propose a new process analytical technology soft sensor that maps directly electrical tomography signals to the relevant parameter to be monitored. The data acquisition and estimation steps occur almost instantaneously, and the final accuracy is very good (R2 = 0,994). SIGNIFICANCE AND NOVELTY: The proposed methodology opens up good prospects for real-time quantitative applications. It was successfully tested on a pilot piping installation where the target property is the interface height between two immiscible fluids.

Type II Odontoid Fractures: Is the Anterior Screw a Good Solution for all Patients? A Case Series of 60 Consecutive Patients.

OBJECTIVE: Type II odontoid fracture is the most common fracture type, and its treatment remains challenging. The objective of this study was to evaluate the results of anterior screw fixation for type II odontoid fractures in patients aged over and below 60 years. METHODS: A retrospective analysis of consecutive patients diagnosed with type II odontoid fractures who were surgically treated using the anterior approach by a single surgeon was conducted. Demographic characteristics, including age, sex, type of fracture, time from trauma to surgery, length of stay (LoS), fusion rate, complications, and reoperation, were evaluated. Surgical outcomes were compared between patients over and below 60 years of age. RESULTS: Sixty consecutive patients underwent odontoid anterior fixation during the analysis period. The mean age of patients was 49.58 ± 23.22 years. Twenty-three (38.3%) patients were aged over 60 years, and the minimum follow-up period was two years. Of the patients, 93.3% developed bone fusion, which was observed in 86.9% of patients over 60 years. Complications related to hardware failure occurred in six (10%) patients. Transient dysphagia was observed in 10% of the cases. Three (5%) patients required reoperation. Patients over 60 years had a significantly increased risk of dysphagia compared with those below 60 years (P = 0.0248). There was no significant difference between the groups regarding nonfusion rate, reoperation rate, or LoS. CONCLUSIONS: Anterior fixation of the odontoid showed high fusion rates with a low rate of complications. It is a technique to be considered for treating type II odontoid fractures in selected cases.

Thirty-day unplanned readmission after spine surgery: analysis of 650 cases / Readmissão não planejada em 30 dias após cirurgias da coluna: análise de 650 casos / Reingreso no planificado a los 30 días después de cirugías de la columna: análisis de 650 casos

ABSTRACT: Objective: Postoperative readmission rates can be used to assess hospital care quality. The rates of unplanned readmission within 30 days after spine surgery are variable in the literature, and no studies have evaluated such rates in a single Latin American center. This study aimed to assess the rate of unplanned hospital readmission within 30 days after a spine surgery at a single Brazilian institution and to identify possible risk factors. Methods: Patients who underwent spine surgery at a single private hospital between January 2018 and December 2020 were retrospectively analyzed, and those with unplanned readmissions within 30 days of discharge were identified. Risk factors were determined, and the reoperation rate was assessed. Results: 650 patients were included in the analysis, and 74 (11.28%) were readmitted within 30 days after surgery. Higher readmission rates were observed after vertebroplasty and surgeries involving spinal or bone tumors. The risk factors found in the series were older age, longer hospital stays, higher ASA scores, instrumented surgeries, diabetes mellitus, and surgeries involving primary or secondary spinal tumors. The most common causes of unplanned readmission were infection and pain. Of the readmissions, 28.37% required a return to the operating room. Conclusions: This study suggests infection and pain management were the most common causes of unplanned readmission after spine surgery. Strategies to improve perioperative and postoperative care are required to reduce unplanned readmissions. Level of Evidence III; Retrospective Comparative Study.

RESUMO: Objetivo: As taxas de readmissão pós-operatórias podem ser usadas para avaliação da qualidade assistencial hospitalar. As taxas de readmissão não planejada em 30 dias após cirurgias de coluna são variáveis na literatura, e não há estudos avaliando tais taxas em centros únicos da América Latina. Este estudo teve como objetivo avaliar as taxas de readmissões não planejadas em 30 dias após cirurgias de coluna em uma única instituição brasileira e identificar possíveis fatores de risco. Métodos: Pacientes submetidos a cirurgias de coluna em um único hospital privado entre janeiro de 2018 e dezembro de 2020 foram avaliados retrospectivamente, e aqueles readmitidos dentro de 30 dias foram identificados. Fatores de risco foram determinados e a taxa de reoperação foi avaliada. Resultados: 650 pacientes foram incluídos na análise, e 74 (11,28%) foram readmitidos dentro de 30 dias após a cirurgia. Maiores taxas de readmissão foram observadas após vertebroplastia e cirurgias envolvendo tumores espinhais ou tumores ósseos. Os fatores de risco encontrados em nossa série foram idade mais elevada, maior tempo de hospitalização, maior escore ASA, cirurgias com instrumentação, diabetes mellitus e cirurgias envolvendo tumores vertebrais primários ou secundários. As causas mais comuns de readmissão não planejada foram infecção e dor. Dentre os pacientes reinternados, 28,37% necessitaram de reoperação. Conclusões: Este estudo sugere que infecção e manejo de dor foram as causas mais comuns de readmissão não planejada após cirurgias de coluna. Estratégias para melhorar os cuidados pre e pós-operatórios são necessárias para reduzir readmissões não planejadas. Nível de Evidência III; Estudo Retrospectivo Comparativo.

RESUMEN: Objetivo: Las tasas de reingreso después de la cirugía de columna son variables y ningún estudio ha evaluado tales tasas en un solo centro latinoamericano. Este estudio tuvo como objetivo evaluar la tasa de reingreso hospitalario no planificado dentro de los 30 días posteriores a la cirugía de columna en una sola institución brasileña e identificar posibles factores de riesgo. Métodos: Se analizaron retrospectivamente los pacientes que se sometieron a cirugía de columna en un solo hospital entre enero de 2018 y diciembre de 2020, y se identificaron aquellos con reingresos no planificados dentro de los 30 días posteriores al alta. Se determinaron los factores de riesgo y se evaluó la tasa de reoperación. Resultados: En el análisis se incluyeron un total de 650 pacientes, y 74 (11,28%) reingresaron dentro de los 30 días posteriores a la cirugía. Se observaron tasas de reingreso más altas después de la vertebroplastia y las cirugías que involucraron tumores espinales u óseos. Los factores de riesgo encontrados en nuestra serie fueron la edad avanzada, la estancia hospitalaria más prolongada, las puntuaciones ASA más altas, las cirugías instrumentadas, la diabetes mellitus y las cirugías de tumores espinales. Las causas más frecuentes de reingreso fueron la infección y el dolor. De los reingresos, el 28,37% requirieron volver al quirófano. Conclusiones: Este estudio sugiere que la infección y el manejo del dolor fueron las causas más comunes de reingreso. Se requieren estrategias para mejorar la atención perioperatoria y posoperatoria y así reducir las readmisiones no planificadas. Nivel de Evidencia III; Estudio comparativo retrospectivo.

Evaluation of the Microbiological Effectiveness of Three Accessible Mask Decontamination Methods and Their Impact on Filtration, Air Permeability and Physicochemical Properties.

The need to secure public health and mitigate the environmental impact associated with the massified use of respiratory protective devices (RPD) has been raising awareness for the safe reuse of decontaminated masks by individuals and organizations. Among the decontamination treatments proposed, in this work, three methods with the potential to be adopted by households and organizations of different sizes were analysed: contact with nebulized hydrogen peroxide (H2O2); immersion in commercial bleach (NaClO) (sodium hypochlorite, 0.1% p/v); and contact with steam in microwave steam-sanitizing bags (steam bag). Their decontamination effectiveness was assessed using reference microorganisms following international standards (issued by ISO and FDA). Furthermore, the impact on filtration efficiency, air permeability and several physicochemical and structural characteristics of the masks, were evaluated for untreated masks and after 1, 5 and 10 cycles of treatment. Three types of RPD were analysed: surgical, KN95, and cloth masks. Results demonstrated that the H2O2 protocol sterilized KN95 and surgical masks (reduction of >6 log10 CFUs) and disinfected cloth masks (reduction of >3 log10 CFUs). The NaClO protocol sterilized surgical masks, and disinfected KN95 and cloth masks. Steam bags sterilized KN95 and disinfected surgical and cloth masks. No relevant impact was observed on filtration efficiency.

0-Dimensional Persistent Homology Analysis Implementation in Resource-Scarce Embedded Systems.

Persistent Homology (PH) analysis is a powerful tool for understanding many relevant topological features from a given dataset. PH allows finding clusters, noise, and relevant connections in the dataset. Therefore, it can provide a better view of the problem and a way of perceiving if a given dataset is equal to another, if a given sample is relevant, and how the samples occupy the feature space. However, PH involves reducing the problem to its simplicial complex space, which is computationally expensive and implementing PH in such Resource-Scarce Embedded Systems (RSES) is an essential add-on for them. However, due to its complexity, implementing PH in such tiny devices is considerably complicated due to the lack of memory and processing power. The following paper shows the implementation of 0-Dimensional Persistent Homology Analysis in a set of well-known RSES, using a technique that reduces the memory footprint and processing power needs of the 0-Dimensional PH algorithm. The results are positive and show that RSES can be equipped with this real-time data analysis tool.

Linear and Non-Linear Soft Sensors for Predicting the Research Octane Number (RON) through Integrated Synchronization, Resolution Selection and Modelling.

The Research Octane Number (RON) is a key quality parameter for gasoline, obtained offline through complex, time-consuming, and expensive standard methods. Measurements are usually only available a few times per week and after long delays, making process control very challenging. Therefore, alternative methods have been proposed to predict RON from readily available data. In this work, we report the development of inferential models for predicting RON from process data collected in a real catalytic reforming process. Data resolution and synchronization were explicitly considered during the modelling stage, where 20 predictive linear and non-linear machine learning models were assessed and compared using a robust Monte Carlo double cross-validation approach. The workflow also handles outliers, missing data, multirate and multiresolution observations, and processes dynamics, among other features. Low RMSE were obtained under testing conditions (close to 0.5), with the best methods belonging to the class of penalized regression methods and partial least squares. The developed models allow for improved management of the operational conditions necessary to achieve the target RON, including a more effective use of the heating utilities, which improves process efficiency while reducing costs and emissions.

Evaluation of Surgically Treated Primary Spinal Cord Tumors in a Single Brazilian Institution: A Case Series Study of 104 Patients.

BACKGROUND: Primary spinal cord tumors are rare and heterogeneous, and their prevalence varies among the studies. Few articles have evaluated the prevalence, characteristics, and histological types of spinal cord tumors in Latin American populations. This study aimed to analyze the histological types and clinical aspects of a series of consecutive patients diagnosed with primary spinal cord tumors who underwent surgical treatment in a single Brazilian institution and to compare them with the literature. METHODS:  This is a case series study, with retrospective analysis of all consecutive adult patients who underwent surgical treatment for primary spinal cord tumors in a single center between January 1997 and April 2021. Data analyzed included age at surgery, sex, anatomical location, histopathological diagnosis, clinical presentation, and neurological status at discharge. RESULTS: A total of 104 patients (53 women [51.0%]; mean age, 49.0 ± 16.7 years [range, 19-87 years]) were included in the analysis. Among the tumors, 83.7% were benign, and 36.5% involved the thoracic spine; intradural extramedullary lesions comprised 52.9% of the tumors, and the most prevalent were schwannomas (26.9%) and meningiomas (18.3%). Among the patients, 55% and 50% presented with pain and motor deficit, respectively, and the deficit improvement rate was greater than the worsening rate at the immediate postoperative period and discharge. CONCLUSIONS: Our series highlights the heterogeneity of primary spinal cord tumors compared to other studies. Further large population studies are necessary to elucidate the epidemiology of this disease.

Machine Learning Techniques Disclose the Combined Effect of Fermentation Conditions on Yeast Mixed-Culture Dynamics and Wine Quality.

The use of yeast starter cultures consisting of a blend of Saccharomyces cerevisiae and non-Saccharomyces yeasts has increased in recent years as a mean to address consumers' demands for diversified wines. However, this strategy is currently limited by the lack of a comprehensive knowledge regarding the factors that determine the balance between the yeast-yeast interactions and their responses triggered in complex environments. Our previous studies demonstrated that the strain Hanseniaspora guilliermondii UTAD222 has potential to be used as an adjunct of S. cerevisiae in the wine industry due to its positive impact on the fruity and floral character of wines. To rationalize the use of this yeast consortium, this study aims to understand the influence of production factors such as sugar and nitrogen levels, fermentation temperature, and the level of co-inoculation of H. guilliermondii UTAD222 in shaping fermentation and wine composition. For that purpose, a Central Composite experimental Design was applied to investigate the combined effects of the four factors on fermentation parameters and metabolites produced. The patterns of variation of the response variables were analyzed using machine learning methods, to describe their clustered behavior and model the evolution of each cluster depending on the experimental conditions. The innovative data analysis methodology adopted goes beyond the traditional univariate approach, being able to incorporate the modularity, heterogeneity, and hierarchy inherent to metabolic systems. In this line, this study provides preliminary data and insights, enabling the development of innovative strategies to increase the aromatic and fermentative potential of H. guilliermondii UTAD222 by modulating temperature and the availability of nitrogen and/or sugars in the medium. Furthermore, the strategy followed gathered knowledge to guide the rational development of mixed blends that can be used to obtain a particular wine style, as a function of fermentation conditions.

Sialic acids expression in newborn rat lungs: implications for pulmonary developmental biology.

Mammalian lung development proceeds during the postnatal period and continues throughout life. Intricate tubular systems of airways and vessels lined by epithelial cells are developed during this process. All cells, and particularly epithelial cells, carry an array of glycans on their surfaces. N-acetylneuraminic (Neu5Ac) and N-glycolylneuraminic (Neu5Gc) acids, two most frequently-occurring sialic acid residues, are essential determinants during development and in the homeostasis of cells and organisms. However, systematic data about the presence of cell surface sialic acids in the postnatal lung and their content is still scarce. In the present study, we addressed the histochemical localization of Neu5Ac > Neu5Gc in 0-day-old rat lungs. Furthermore, both residues were separated, identified and quantified in lung membranes isolated from 0-day-old rat lungs using high-performance liquid chromatography (HPLC) methodologies. Finally, we compared these results with those previously reported by us for adult rat lungs. The Neu5Ac > Neu5Gc residues were located on the surface of ciliated and non-ciliated cells and the median values for both residues in the purified lung membranes of newborn rats were 5.365 and 1.935 µg/mg prot., respectively. Comparing these results with those reported for the adults, it was possible to observe a significant difference between the levels of Neu5Ac and Neu5Gc (p < 0.001). A more substantial change was found for the case of Neu5Ac. The preponderance of Neu5Ac and its expressive increase during the postnatal development points towards a more prominent role of this residue. Bearing in mind that sialic acids are negatively charged molecules, the high content of Neu5Ac could contribute to the formation of an anion "shield" and have a role in pulmonary development and physiology.

Estudo exploratório sobre a utilização da Colostroterapia em Unidade Neonatal de uma maternidade brasileira / Exploratory study on the use of Colostrum therapy in a brazilian maternity hospital's Neonatal Unit

Estudo exploratório para verificar a utilização da colostroterapia em recém-nascidos de muito baixo peso, em unidade neonatal de maternidade de médio porte, por meio da avaliação de prontuários. Dos 108 prontuários avaliados, 56,5% dos neonatos eram do sexo feminino, com média de peso e idade gestacional ao nascimento de 1091,9 g (DP=263,7g) e 29 semanas/2dias (DP=2semanas/6dias), respectivamente. A colostroterapia foi utilizada em 25,9% dos pacientes, sendo que em 96,4% dos casos a administração foi por via oral. O uso de terapia colostral foi associado significativamente a variáveis neonatais como idade gestacional, peso ao nascer e óbito neonatal (p = 0,001, p < 0,001, e p < 0,001). Não havendo protocolo estabelecido para guiar a prescrição da colostroterapia, esta ocorreu principalmente para prematuros de menor peso, mais imaturos ou mais doentes, com maior risco de morbidade e mortalidade.

Exploratory study of colostrum therapy use in very low birth weight newborns in a neonatal unit by the analysis of medical records. The 108 patients under study were predominantly female (56,5%), had a mean weight and gestational age at birth of 1091.9 g (SD=263.7g) and 29 weeks/2 days (SD=2 weeks/6 days), respectively. Colostrum therapy was used for 29.5% of the patients mostly by oral administration (96.4%). The use of colostrum therapy was significantly associated with low gestational age and weight at birth and with neonatal death (p = 0.001, p < 0.001 and p < 0.001). As there was no established protocol to guide colostrum therapy prescription in the neonatal unit, the therapy was apparently chosen to be used for more immature or sicker babies, with a greater morbidity or mortality risk.

Presence of N-acetylneuraminic acid in the lung during postnatal development.

Sialic acids, particularly N-acetylneuraminic acid (Neu5Ac), are present as terminal components of rich and complex oligosaccharide chains, which are termed glycans, and are exhibited on the cell surfaces, especially on epithelial cells. Crucial in the 'social behavior' of the cell, sialic acids play vital roles in many physiological and pathological phenomena. The aim of the present study was to separate, identify, and quantify Neu5Ac in purified lung membranes from 4-, 14-, and 21-day-old animals, followed by the statistical analysis of these results with our previously reported data (0-day-old and adult results). Complementary, ultrastructural methodologies were used. The differences in the Neu5Ac values obtained across the examined postnatal-lung development relevant ages studied were found to be statistically significant. A substantial increase in the mean level of this compound was found during the period of 'bulk' alveolarization, which takes place from postnatal day 4 to 14 (P4-P14). The comparison of the mean levels of Neu5Ac, during microvascular maturation (mainly between P12 and P21), reveals that the difference, although statistically significant, is the least significant difference among all the pair-wise differences between the developmental stages. The presence of sub-terminal N-acetylgalactosamine (GalNAc)/Galactose (Gal) residues with terminal sialic acids on the bronchioloalveolar cell surfaces was confirmed using lung ultra-thin sections of adult and 0-day-old animals. These results showed that, although Neu5Ac levels increase throughout postnatal lung development, this sialic acid was substantially added to epithelial cell surfaces during the "bulk" alveolarization period, while its presence was less important during the microvascular maturation period. Bearing in mind that sialic acids are negatively charged and create charge repulsions between adjacent cells, we hypothesized that they can substantially contribute to postnatal alveolar formation and maturation.

Multi-target optimization of solid phase microextraction to analyse key flavour compounds in wort and beer.

Despite the literature comprises numerous studies dealing with the analysis of wort and beer flavour-related compounds by HS-SPME followed by GC-MS quantification, no generalized consensus exists regarding the optimal conditions for the extraction procedure. The complex chemistry nature of these matrices, the number of analytes, as well as the number and interactions among parameters affecting the extraction performance, requires the adoption of optimal experimental design protocols. This aspect is often overlooked and often not properly addressed in practice. Therefore, in the present work, the optimal conditions under which a range of wort and beer analytes can be extracted and quantified were analysed. The optimal extraction conditions were presented at two levels of aggregation: global (untargeted) and key-flavour analysis. Experimental data was generated by Definitive-Screening-Design, followed by model development and optimization. Both approaches were compared and critically analysed. For vicinal-diketones group, a complete validation study for the optimal conditions is presented.

Quality by design in pharmaceutical manufacturing: A systematic review of current status, challenges and future perspectives.

Quality by Design (QbD) was originated in the broad domain of Quality Management and was recently adapted and formalized in specific terms for assisting pharmaceutical companies efforts towards market and operational excellence. However, despite some impressive success stories, the pharmaceutical industry have not yet fully embraced QbD, particularly in routine commercial manufacturing (Rantanen and Khinast, 2015; Puñal Peces et al., 2016). In this review, we aim to analyse the current state of implementation of QbD methodologies and tools in the pharmaceutical industry, extracting patterns and trends and identifying gaps and opportunities that may be considered to improve QbD adoption. For this purpose, a critical analysis of 60 research papers was performed, whose contents were classified, compared and summarized at different abstraction levels. Our analysis reveals the following tools as the frequently adopted for conducting each activity: Risk Assessment (RA) - Ishikawa Diagram, Failure Mode and Effects Analysis (FMEA) and Risk Estimation Matrix (REM); Screening Design of Experiments (DoE) - 2-level Full and Fractional Factorial Designs; Optimisation DoE - Central Composite Design (CCD). Emerging trends include the growing interest in quantifying and managing the impact of raw materials' attributes variability on process and product, as well as the development of Retrospective QbD approaches (rQbD) in complement to standard QbD.

Reference values for the carbon monoxide diffusion (transfer factor) in a brazilian sample of white race. / Valores de referência para a difusão do monóxido de carbono (fator de transferência) em uma amostra brasileira da raça branca.

OBJECTIVE: To derive reference values from white race adults, for DCO in a sample from different sites in Brazil, through the same equipment model (Sensormedics), and compare the results with the derivatives from Crapo, Miller, Neder equations and from the Global Lung Initiative (GLI) proposal. METHODS: The tests were performed according to the norms suggested by ATS/ERS in 2005 in six Brazilian cities, with 120 adult volunteers of each gender, non-smokers, without referred anemia and without lung or cardio diseases. The expected values were derived from linear regressions and the differences between the values forecasted by some authors and the ones observed in the current study were calculated. RESULTS: Among men, the age varied between 25 and 88 years old, and the height varied between 140 and 176 cm. DCO was correlated significantly and positively with the height and negatively with the age. The values forecasted by Crapo, Neder, and Miller equations were higher in comparison with the ones obtained by the current study (p<0.01) in both genders. Among men, the values did not differ when compared to the ones calculated by GLI (p=0.29); among women, the values derived by GLI were slightly higher: 0.99 ml/min/mmHg (p<0.01). CONCLUSION: new values forecasted for DCO were derived in a sample of white adults in Brazil. The forecasted values are similar to the ones complied by GLI equations and differ from the previously proposed equations.

OBJETIVO: Derivar valores de referência em adultos brancos para a difusão do monóxido de carbono (DCO) em uma amostra de diferentes locais do Brasil por um mesmo modelo de equipamento (Sensormedics) e comparar os resultados com os derivados pelas equações de Crapo, Miller e Neder, e da proposta pelo Global Lung Initiative (GLI). MÉTODOS: Os testes foram realizados de acordo com as normas sugeridas pela ATS/ERS, em 2005, em seis cidades brasileiras, em 120 voluntários adultos de cada sexo, não fumantes, sem anemia referida e sem doenças pulmonares ou cardíacas. Os previstos foram derivados por regressões lineares e as diferenças entre os valores previstos por alguns autores e os observados no estudo atual foram calculadas. RESULTADOS: Nos homens, a idade variou de 25 a 88 anos e a estatura, de 156 a 189 cm. Nas mulheres, a idade variou de 21 a 92 anos e a estatura, de 140 a 176 cm. A DCO se correlacionou de maneira significativa positivamente com a estatura e negativamente com a idade. Os valores previstos pelas equações de Crapo, Neder e Miller foram maiores em comparação aos obtidos pelo estudo atual (p<0,01) em ambos os sexos. Nos homens, os valores não diferiram quando comparados aos calculados pelo GLI (p=0,29); nas mulheres, os valores derivados pelo GLI foram levemente maiores: 0,99 mL/min/mmHg (p<0,01). CONCLUSÕES: Novos valores previstos para a DCO foram derivados em uma amostra de adultos brancos no Brasil. Os valores previstos são semelhantes aos compilados pelas equações GLI e diferem de equações propostas anteriormente.

Valores de referência para a difusão do monóxido de carbono (fator de transferência) em uma amostra brasileira da raça branca / Reference values for the carbon monoxide diffusion (transfer factor) in a brazilian sample of white race

RESUMO Objetivo Derivar valores de referência em adultos brancos para a difusão do monóxido de carbono (DCO) em uma amostra de diferentes locais do Brasil por um mesmo modelo de equipamento (Sensormedics) e comparar os resultados com os derivados pelas equações de Crapo, Miller e Neder, e da proposta pelo Global Lung Initiative (GLI). Métodos Os testes foram realizados de acordo com as normas sugeridas pela ATS/ERS, em 2005, em seis cidades brasileiras, em 120 voluntários adultos de cada sexo, não fumantes, sem anemia referida e sem doenças pulmonares ou cardíacas. Os previstos foram derivados por regressões lineares e as diferenças entre os valores previstos por alguns autores e os observados no estudo atual foram calculadas. Resultados Nos homens, a idade variou de 25 a 88 anos e a estatura, de 156 a 189 cm. Nas mulheres, a idade variou de 21 a 92 anos e a estatura, de 140 a 176 cm. A DCO se correlacionou de maneira significativa positivamente com a estatura e negativamente com a idade. Os valores previstos pelas equações de Crapo, Neder e Miller foram maiores em comparação aos obtidos pelo estudo atual (p<0,01) em ambos os sexos. Nos homens, os valores não diferiram quando comparados aos calculados pelo GLI (p=0,29); nas mulheres, os valores derivados pelo GLI foram levemente maiores: 0,99 mL/min/mmHg (p<0,01). Conclusões Novos valores previstos para a DCO foram derivados em uma amostra de adultos brancos no Brasil. Os valores previstos são semelhantes aos compilados pelas equações GLI e diferem de equações propostas anteriormente.

ABSTRACT Objective To derive reference values from white race adults, for DCO in a sample from different sites in Brazil, through the same equipment model (Sensormedics), and compare the results with the derivatives from Crapo, Miller, Neder equations and from the Global Lung Initiative (GLI) proposal. Methods The tests were performed according to the norms suggested by ATS/ERS in 2005 in six Brazilian cities, with 120 adult volunteers of each gender, non-smokers, without referred anemia and without lung or cardio diseases. The expected values were derived from linear regressions and the differences between the values forecasted by some authors and the ones observed in the current study were calculated. Results Among men, the age varied between 25 and 88 years old, and the height varied between 140 and 176 cm. DCO was correlated significantly and positively with the height and negatively with the age. The values forecasted by Crapo, Neder, and Miller equations were higher in comparison with the ones obtained by the current study (p<0.01) in both genders. Among men, the values did not differ when compared to the ones calculated by GLI (p=0.29); among women, the values derived by GLI were slightly higher: 0.99 ml/min/mmHg (p<0.01). Conclusion new values forecasted for DCO were derived in a sample of white adults in Brazil. The forecasted values are similar to the ones complied by GLI equations and differ from the previously proposed equations.

Biomechanical evaluation of interbody fixation with secondary augmentation: lateral lumbar interbody fusion versus posterior lumbar interbody fusion.

BACKGROUND: Many approaches to the lumbar spine have been developed for interbody fusion. The biomechanical profile of each interbody fusion device is determined by the anatomical approach and the type of supplemental internal fixation. Lateral lumbar interbody fusion (LLIF) was developed as a minimally invasive technique for introducing hardware with higher profiles and wider widths, compared with that for the posterior lumbar interbody fusion (PLIF) approach. However, the biomechanics of the interbody fusion construct used in the LLIF approach have not been rigorously evaluated, especially in the presence of secondary augmentation. METHODS: Spinal stability of 21 cadaveric lumbar specimens was compared using standard nondestructive flexibility studies [mean range of motion (ROM), lax zone (LZ), stiff zone (SZ) in flexion-extension, lateral bending, and axial rotation]. Non-paired comparisons were made among four conditions: (I) intact; (II) with unilateral interbody + bilateral pedicle screws (BPS) using the LLIF approach (referred to as the LLIF construct); (III) with bilateral interbody + BPS using the PLIF approach (referred to as the PLIF construct); and (IV) with no lumbar interbody fusion (LIF) + BPS (referred to as the no-LIF construct). RESULTS: With bilateral pedicle screw-rod fixation, stability was equivalent between PLIF and LLIF constructs in lateral bending and flexion-extension. PLIF and LLIF constructs had similar biomechanical profiles, with a trend toward less ROM in axial rotation for the LLIF construct. CONCLUSIONS: LLIF and PLIF constructs had similar stabilizing effects.