Effect of time and photoactivated face on bond strength of brackets and on degree of monomer conversion.

OBJECTIVE: To evaluate the effect of four different photoactivation protocols (according to "photoactivated faces" - mesial/distal, cervical/incisal or center - and "photoactivation time" - 6-3 s) of a high-power photo activator (Valo Cordless®-Ultradent) on the shear bond strength (SBS) between metal brackets and dental enamel and on the degree of conversion (DC) of an orthodontic resin. MATERIALS AND METHODS: 40 bovine incisor crowns were randomly assigned to 4 groups (n = 10). The brackets were bonded with Transbond XT® resin using 4 protocols according to the "photoactivation protocol" factor (which was subdivided into photoactivated faces and photoactivation time): V3C = 3 s + center; V6C = 6 s + center; V3M3D = 3 s on mesial + 3 s on distal; V3C3I = 3 s on cervical + 3 s on incisal. All the samples were stored for 4 months (water,37ºC) and then subjected to a SBS test (100KgF,1 mm/min). 40 resin discs were made to evaluate the monomer degree of conversion. Data from the SBS and DC were assessed by One-way ANOVA and Tukey's test (5%). Bond failures were analyzed according to the Adhesive Remnant Index (ARI) and evaluated by the Kruskal-Wallis test (5%). RESULTS: There was a statistically significant difference (p = 0.008) in the One-way ANOVA result for SBS values between all groups, but the protocols showed statistically similar results (p ≥ 0.05-Tukey's tests) concerning the photoactivated faces (V6C, V3M3D and V3C3I) and photoactivation time (V3C and V6C) factors individually. There was no statistically significant difference (p ≥ 0.05) in the One-way ANOVA result for DC values. CONCLUSION: The SBS and DC values will vary depending on the protocol applied. CLINICAL RELEVANCE: It is possible to maintain the bracket fixation quality with the use of a high-power LED photo activator associated with a shorter photoactivation time. However, it is assumed that not all types of protocols that might be applied will provide quality bonding, such as V3C, V3M3D and V3C3I, which may - depending on the SBS and DC values - affect the final treatment time, due to brackets debonding, or increase of possibility of damage to dental enamel during bracket removal. Clinical studies are suggested to confirm the hypotheses of this research.

Caffeine induces alveolar bone loss in rats submitted to orthodontic movement via activation of receptor activator of nuclear factor Ò¡B, receptor activator of nuclear factor Ò¡B ligand, and osteoprotegerin pathway.

INTRODUCTION: Caffeine is a widely consumed substance with several effects on bone metabolism. This study aimed to investigate the effect of caffeine on the bone tissue of rats submitted to orthodontic movement. METHODS: Twenty-five male Wistar rats underwent orthodontic movement (21 days) of the first permanent maxillary molars on the left side. The experimental group (caffeine; n = 13) and control group (n = 12) received caffeine and water, respectively, by gavage. Microcomputed tomography was performed to analyze orthodontic movement. Histologic analysis of the inflammatory infiltrate and osteoclast count by tartrate-resistant acid phosphatase were conducted. Maxilla tissue was evaluated for receptor activator of nuclear factor Ò¡B (RANK), RANK ligand (RANKL), and osteoprotegerin by immunohistochemistry. RESULTS: Caffeine exhibited a lower bone volume/tissue volume ratio (78.09% ± 5.83%) than the control (86.84% ± 4.89%; P <0.05). Inflammatory infiltrate was increased in the caffeine group compared with the control group (P <0.05). A higher number of tartrate-resistant acid phosphatase-positive cells was observed in the caffeine (9.67 ± 1.73) than in the control group (2.66 ± 0.76; P <0.01). Immunoexpression of RANK and RANKL in the caffeine group was greater than the control (P <0.05). CONCLUSIONS: The use of caffeine thermogenic induces alveolar bone loss in rats submitted to orthodontic movement via activation of RANK, RANKL, and osteoprotegerin signaling pathways.

Association between muscle quality index and pulmonary function in post-COVID-19 subjects.

BACKGROUND: The SARS-CoV2 pandemic impacted many critically ill patients, causing sequelae, affecting lung function, and involving the musculoskeletal system. We evaluated the association between lung function and muscle quality index in severely ill post-COVID-19 patients. METHODS: A cross-sectional study was conducted on a post-COVID-19 cohort at a third-level center. The study included patients who had experienced severe-to-critical COVID-19. Anthropometric measurements, such as body mass index (BMI) and handgrip strength, were obtained to calculate the muscle quality index (MQI). Additionally, spirometry, measurements of expiratory and inspiratory pressure, and an assessment of DLCO in the lungs were performed. The MQI was categorized into two groups: low-MQI (below the 50th percentile) and high-MQI (above the 50th percentile), based on sex. Group differences were analyzed, and a multivariate linear regression analysis was performed to assess the association between respiratory function and MQI. RESULTS: Among the 748 patients analyzed, 61.96% required mechanical ventilation, and the median hospital stay was 17 days. In patients with a low MQI, it was observed that both mechanical respiratory function and DLCO were lower. The multivariate analysis revealed significantly lower findings in mechanical respiratory function among patients with a low MQI. CONCLUSION: The Low-MQI is an independent predictor associated with pulmonary function parameters in subjects with Post-COVID-19 syndrome.

CG Dinucleotide Removal in Bioluminescent and Fluorescent Reporters Improves HIV-1 Replication and Reporter Gene Expression for Dual Imaging in Humanized Mice.

Visualizing the transmission and dissemination of human immunodeficiency virus type 1 (HIV-1) in real time in humanized mouse models is a robust tool to investigate viral replication during treatments and in tissue reservoirs. However, the stability and expression of HIV-1 reporter genes are obstacles for long-term serial imaging in vivo. Two replication-competent CCR5-tropic HIV-1 reporter constructs were created that encode either nanoluciferase (nLuc) or a near-infrared fluorescent protein (iRFP) upstream of nef. HIV-1 reporter virus replication and reporter gene expression was measured in cell culture and in humanized mice. While reporter gene expression in vivo correlated initially with plasma viremia, expression decreased after 4 to 5 weeks despite high plasma viremia. The reporter genes were codon optimized to remove cytosine/guanine (CG) dinucleotides, and new CO-nLuc and CO-iRFP viruses were reconstructed. Removal of CG dinucleotides in HIV-1 reporter viruses improved replication in vitro and reporter expression in vivo and ex vivo. Both codon-optimized reporter viruses could be visualized during coinfection and in vivo reporter gene expression during treatment failure preceded detection of plasma viremia. While the dynamic range of CO-iRFP HIV-1 was lower than that of CO-nLuc HIV-1, both viruses could have utility in studying and visualizing HIV-1 infection in humanized mice. IMPORTANCE Animal models are important for studying HIV-1 pathogenesis and treatments. We developed two viruses each encoding a reporter gene that can be expressed in cells after infection. This study shows that HIV-1 infection can be visualized by noninvasive, whole-body imaging in mice with human immune cells over time by reporter expression. We improved reporter expression to reflect HIV-1 replication and showed that two viral variants can be tracked over time in the same animal and can predict failure of antiretroviral therapy to suppress virus.

A perspective on Quality-by-Control (QbC) in pharmaceutical continuous manufacturing.

The Quality-by-Design (QbD) guidance issued by the US Food and Drug Administration (FDA) has catalyzed the modernization of pharmaceutical manufacturing practices including the adoption of continuous manufacturing. Active process control was highlighted recently as a means to improve the QbD implementation. This advance has since been evolving into the concept of Quality-by-Control (QbC). In this study, the concept of QbC is discussed, including a definition of QbC, a review of the recent developments towards the QbC, and a perspective on the challenges of QbC implementation in continuous manufacturing. The QbC concept is demonstrated using a rotary tablet press, integrated into a pilot scale continuous direct compaction process. The results conclusively showed that active process control, based on product and process knowledge and advanced model-based techniques, including data reconciliation, model predictive control (MPC), and risk analysis, is indispensable to comprehensive QbC implementation, and ensures robustness and efficiency.

Resilience and risk analysis of fault-tolerant process control design in continuous pharmaceutical manufacturing.

The shift from batch to continuous manufacturing, which is occurring in the pharmaceutical manufacturing industry has implications on process safety and product quality. It is now understood that fault-tolerant process control of critical process parameters (CPPs) and critical quality attributes (CQAs) is of paramount importance to the realization of safe operations and quality products. In this study, a systematic framework for fault-tolerant process control system design, analysis, and evaluation of pharmaceutical continuous oral solid dosage manufacturing is proposed. The framework encompasses system identification, controller design and analysis (controllability, stability, resilience, etc.), hierarchical three-level control structures (model predictive control, state estimation, data reconciliation, etc.), risk mapping, assessment and planning (Risk MAP) strategies, and control performance evaluation. The key idea of the proposed framework is to identify the potential risks associated with the control system design itself, the material property variations, and other process uncertainties, under which the control strategies must be evaluated. The framework is applied to a continuous direct compaction process, specifically the feeding-blending subsystem, wherein the major source of variance in the process operation and product quality arises. It is demonstrated, using simulations and experimentally, that the process operation failures and product quality variations in the feeding-blending system can be mitigated and managed through the proposed systematic fault-tolerant process control system design and risk analysis framework.

TEN-YEAR OUTCOMES OF TIPS FOR BUDD-CHIARI SYNDROME: SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: Budd-Chiari syndrome (BCS) results from the obstruction of the hepatic venous flow, usually at the level of the hepatic vein or inferior vena cava. When left untreated, it can progress with several complications, including liver cirrhosis. Transjugular intrahepatic portosystemic shunt (TIPS) appears to be effective in a subgroup of BCS patients. OBJECTIVE: To perform a systematic review and meta-analysis of TIPS effectiveness in BCS treatment, considering the survival rate, reduction in portosystemic pressure, need for liver transplantation, technical failure, and shunt dysfunction for up to 10 years of follow-up. METHODS: We evaluated 17 studies published in PubMed, Science Direct, Web of Science, and SCOPUS databases, which used TIPS as a treatment for BCS, comprising 618 subjects between 18 and 78 years old. We assessed the bias risk by the NOS, NHI, and JBI scales for cohort stu-dies, before-after studies, and case series, respectively. We conducted the meta-analyses by extracting the number of events and the total patients evaluated to perform the proportion meta-analyses using the R software ("meta" package - version 4.9-6). RESULTS: The pooled results (95%CI) showed a 19% (25.9-12.5%) rate of portosystemic pressure reduction, 6% (1-12%) rate for the need for liver transplants despite the use of TIPS, 2% (1-6%) technical failure rate, 30% (18-46%) shunt dysfunction rate, and 88% (81-93%) for the mean frequency of patients alive between 1 and 10 years after the procedure. We stratified survival rate and found an 86% (74-93%) prevalence of living subjects during less than five years, 92% (83-97%) at five years, and a 77% frequency (68-83%) of patients alive ten years after the TIPS placement. CONCLUSION: TIPS is an effective treatment for BCS, providing a high 10-year frequency of living patients and a significant decrease in portosystemic pressure. The need for liver transplants after TIPS and the technical failure rate is low.

Exploring the association between Trypanosoma cruzi infection in rural communities and environmental changes in the southern Gran Chaco.

The association between land use and land cover changes between 1979-2004 in a 2.26-million-hectare area south of the Gran Chaco region and Trypanosoma cruzi infection in rural communities was analysed. The extent of cultural land, open and closed forests and shrubland up to 3,000 m around rural communities in the north, northwest and west of the province of Córdoba was estimated using Landsat satellite imagery. The T. cruzi prevalence was estimated with a cross-sectional serological survey conducted in the rural communities. The land cover showed the same patterns in the 1979, 1999 and 2004 satellite imagery in both the northwest and west regions, with shrinking regions of cultured land and expanding closed forests away from the community. The closed forests and agricultural land coverage in the north region showed the same trend as in the northwest and west regions in 1979 but not in 1999 or 2004. In the latter two years, the coverage remote from the communities was either constant or changed in opposite ways from that of the northwest and west regions. The changes in closed forests and cultured vegetation alone did not have a significant, direct relationship with the occurrence of rural communities with at least one person infected by T. cruzi. This study suggests that the overall decrease in the prevalence of T. cruzi is a consequence of a combined effect of vector control activities and changes in land use and land cover.

ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing the death of more than 5 million people worldwide. The genetic background represents a factor that predisposes the way the host responds to SARS-CoV-2 infection. In this sense, genetic variants of ACE and ACE2 could explain the observed interindividual variability to COVID-19 outcomes. In order to improve the understanding of how genetic variants of ACE and ACE2 are involved in the severity of COVID-19, we included a total of 481 individuals who showed clinical manifestations of COVID-19 and were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood and saliva samples. ACE insertion/deletion polymorphism was evaluated by the high-resolution melting method; ACE single-nucleotide polymorphism (SNP) (rs4344) and ACE2 SNPs (rs2285666 and rs2074192) were genotyped using TaqMan probes. We assessed the association of ACE and ACE2 polymorphisms with disease severity using logistic regression analysis adjusted by age, sex, hypertension, type 2 diabetes, and obesity. The severity of the illness in our study population was divided as 31% mild, 26% severe, and 43% critical illness; additionally, 18% of individuals died, of whom 54% were male. Our results showed in the codominant model a contribution of ACE2 gene rs2285666 T/T genotype to critical outcome [odds ratio (OR) = 1.83; 95%CI = 1.01-3.29; p = 0.04] and to require oxygen supplementation (OR = 1.76; 95%CI = 1.01-3.04; p = 0.04), in addition to a strong association of the T allele of this variant to develop critical illness in male individuals (OR = 1.81; 95%CI = 1.10-2.98; p = 0.02). We suggest that the T allele of rs2285666 represents a risk factor for severe and critical outcomes of COVID-19, especially for men, regardless of age, hypertension, obesity, and type 2 diabetes.

Metabolic Reprogramming in SARS-CoV-2 Infection Impacts the Outcome of COVID-19 Patients.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection triggers inflammatory clinical stages that affect the outcome of patients with coronavirus disease 2019 (COVID-19). Disease severity may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. The aim of this study was to characterize the profile of amino acids and acylcarnitines in COVID-19 patients. A multicenter, cross-sectional study was carried out. A total of 453 individuals were classified by disease severity. Levels of 11 amino acids, 31 acylcarnitines, and succinylacetone in serum samples were analyzed by electrospray ionization-triple quadrupole tandem mass spectrometry. Different clusters were observed in partial least squares discriminant analysis, with phenylalanine, alanine, citrulline, proline, and succinylacetone providing the major contribution to the variability in each cluster (variable importance in the projection >1.5). In logistic models adjusted by age, sex, type 2 diabetes mellitus, hypertension, and nutritional status, phenylalanine was associated with critical outcomes (odds ratio=5.3 (95% CI 3.16-9.2) in the severe vs. critical model, with an area under the curve of 0.84 (95% CI 0.77-0.90). In conclusion the metabolic imbalance in COVID-19 patients might affect disease progression. This work shows an association of phenylalanine with critical outcomes in COVID-19 patients, highlighting phenylalanine as a potential metabolic biomarker of disease severity.

INTRA- AND INTER-RATER RELIABILITY OF A BIOPHOTOGRAMMETRIC ASSESSMENT PROTOCOL FOR PRETERM INFANTS.

OBJECTIVE: To measure the intra- and inter-rater reliability of a biophotogrammetric assessment protocol for thoracoabdominal motion in preterm infants. METHODS: This is an analytical cross-sectional study. Footage of 40 preterm infants was made in two views (lateral and anterior). The babies were placed in the supine position, with retroverted pelvis and semiflexed knees. Acrylic markers were positioned on surgical tape in eight predetermined anatomical points. We analyzed 4 variables in lateral view and 11 in anterior view (angular and linear) (ImageJ®), divided into two stages: 1. same frames - three blinded evaluators analyzed frames previously selected by the main researcher (inter-rater analysis 1), reviewing these same frames after 15 days (intra-rater analysis 1); 2. different frames - each evaluator selected the frames from the original video and repeated the protocol (inter-rater analysis 2), with a review after 15 days (intra-rater analysis 2). In stage 2, we tested the reliability of the entire process, from image selection to the analysis of variables. Data agreement and reproducibility were obtained by the intraclass correlation coefficient (ICC). RESULTS: Agreement was high, particularly in angular variables (ICC 0.82 to 0.99). Linear variables ranged between very good and excellent in analysis 1 (same frames: ICC 0.64 to 0.99) and analysis 2 (different frames: ICC 0.44 to 0.89). CONCLUSIONS: The present study suggests that the proposed protocol for the thoracoabdominal motion analysis of preterm neonates has high reliability.

Sensor Network Robustness Using Model-Based Data Reconciliation for Continuous Tablet Manufacturing.

Advances in continuous manufacturing in the pharmaceutical industry necessitate reliable process monitoring systems that are capable of handling measurement errors inherent in all sensor technologies and detecting measurement outliers to ensure operational reliability. The purpose of this work was to demonstrate data reconciliation (DR) and gross error detection methods as real-time process management tools to accomplish robust process monitoring. DR mitigates the effects of random measurement errors, while gross error detection identifies nonrandom sensor malfunctions. DR is an established methodology in other industries (i.e., oil and gas) and was recently investigated for use in drug product continuous manufacturing. This work demonstrates the development and implementation of model-based steady-state data reconciliation on 2 different end-to-end continuous tableting lines: direct compression and dry granulation. These tableting lines involve different equipment and sensor configurations, with sensor network redundancy achieved using equipment-embedded sensors and in-line process analytical technology tools for the critical process parameters and critical quality attributes. The nonlinearity of the process poses additional challenges to solve the steady-state data reconciliation optimization problem in real time. At-line and off-line measurements were used to validate the framework results.

Eficácia do TIPS em 10 anos na síndrome de Budd-Chiari: revisão sistemática e metanálise / Ten-year outcomes of tips for budd-chiari syndrome: systematic review and meta-analysis

ABSTRACT Background: Budd-Chiari syndrome (BCS) results from the obstruction of the hepatic venous flow, usually at the level of the hepatic vein or inferior vena cava. When left untreated, it can progress with several complications, including liver cirrhosis. Transjugular intrahepatic portosystemic shunt (TIPS) appears to be effective in a subgroup of BCS patients. Objective: To perform a systematic review and meta-analysis of TIPS effectiveness in BCS treatment, considering the survival rate, reduction in portosystemic pressure, need for liver transplantation, technical failure, and shunt dysfunction for up to 10 years of follow-up. Methods: We evaluated 17 studies published in PubMed, Science Direct, Web of Science, and SCOPUS databases, which used TIPS as a treatment for BCS, comprising 618 subjects between 18 and 78 years old. We assessed the bias risk by the NOS, NHI, and JBI scales for cohort stu­dies, before-after studies, and case series, respectively. We conducted the meta-analyses by extracting the number of events and the total patients evaluated to perform the proportion meta-analyses using the R software ("meta" package - version 4.9-6). Results: The pooled results (95%CI) showed a 19% (25.9-12.5%) rate of portosystemic pressure reduction, 6% (1-12%) rate for the need for liver transplants despite the use of TIPS, 2% (1-6%) technical failure rate, 30% (18-46%) shunt dysfunction rate, and 88% (81-93%) for the mean frequency of patients alive between 1 and 10 years after the procedure. We stratified survival rate and found an 86% (74-93%) prevalence of living subjects during less than five years, 92% (83-97%) at five years, and a 77% frequency (68-83%) of patients alive ten years after the TIPS placement. Conclusion: TIPS is an effective treatment for BCS, providing a high 10-year frequency of living patients and a significant decrease in portosystemic pressure. The need for liver transplants after TIPS and the technical failure rate is low.

RESUMO Contexto: A síndrome de Budd-Chiari (SBC) é resultante da obstrução do fluxo venoso hepático, usualmente no nível da veia hepática ou da veia cava inferior. Quando não tratada, pode evoluir com complicações, incluindo a cirrose hepática. O tratamento com TIPS parece ser eficaz em um subgrupo de pacientes. Objetivo: Realizar uma revisão sistemática e meta-análise da eficácia do TIPS no tratamento da síndrome de Budd-Chiari, considerando sobrevida, redução de pressão portossistêmica, necessidade de transplante hepático, falha técnica e disfunção no shunt em 10 anos de seguimento. Métodos: Foram avaliados 17 estudos publicados nas bases de dados PubMed, Science direct, Web of Science e SCOPUS, que utilizaram TIPS como tratamento da SBC, correspondendo a um total de 618 pacientes, entre 18 e 78 anos. O risco de viés foi avaliado pelas escalas de NOS, NHI e JBI, para estudos de coorte, antes e depois e séries de casos, respectivamente. As meta-análises foram conduzidas, extraindo o número de eventos e o total de pacientes avaliados para realizar as meta-análises de proporções usando o software R, com o pacote "meta" (versão 4.9-6). Resultados: Os resultados agrupados (IC de 95%) foram de 19% (25,9-12,5%) para a taxa de redução da pressão portossistêmica, 6% (1-12%) para a taxa de necessidade de transplantes hepáticos a despeito do uso do TIPS, 2% (1-6%) para a taxa de falha técnica, 30% (18-46%) para a taxa de disfunção do shunt e 88% (81-93%) para a sobrevida entre 1 e 10 anos depois do procedimento. Estratificando essa sobrevida, foi detectada 86% (74-93%) no período menor do que 5 anos, 92% (83-97%) com 5 anos, e 77% (68-83%) de frequência de pacientes vivos 10 anos após a realização do TIPS. Conclusão: O TIPS é um tratamento eficaz para a SBC, proporcionando elevada sobrevida em 10 anos e uma diminuição significativa da pressão portossistêmica. A necessidade de transplantes de fígado após TIPS e a taxa de falha técnica são baixas.

Steady-State Data Reconciliation Framework for a Direct Continuous Tableting Line.

Purpose: Reliable process monitoring in real-time remains a challenge for the pharmaceutical industry. Dealing with random and gross errors in the process measurements in a systematic way is a potential solution. In this paper, we present a process model-based framework, which for given sensor network and measurement uncertainties will predict the most likely state of the process. Thus, real-time process decisions, whether for process control or exceptional events management, can be based on the most reliable estimate of the process state. Methods: Reliable process monitoring is achieved by using data reconciliation (DR) and gross error detection (GED) to mitigate the effects of random measurement errors and non-random sensor malfunctions. Steady-state data reconciliation (SSDR) is the simplest forms of DR but offers the benefits of short computational times. We also compare and contrast the model-based DR approach (SSDR-M) to the purely data-driven approach (SSDR-D) based on the use of principal component constructions. Results: We report the results of studies on a pilot plant-scale continuous direct compression-based tableting line at steady-state in two subsystems. If the process is linear or mildly nonlinear, SSDR-M and SSDR-D give comparable results for the variables estimation and GED. SSDR-M also complies with mass balances and estimate unmeasured variables. Conclusions: SSDR successfully estimates the true state of the process in presence of gross errors, as long as steady state is maintained and the redundancy requirement is met. Gross errors are also detected while using SSDR-M or SSDR-D. Process monitoring is more reliable while using the SSDR framework.

Data reconciliation in the Quality-by-Design (QbD) implementation of pharmaceutical continuous tablet manufacturing.

Data provided by in situ sensors is always affected by some level of impreciseness as well as uncertainty in the measurements due to process operation disturbance or material property variance. In-process data precision and reliability should be considered when implementing active product quality control and real-time process decision making in pharmaceutical continuous manufacturing. Data reconciliation is an important strategy to address such imperfections effectively, and to exploit the data redundancy and data correlation based on process understanding. In this study, a correlation between tablet weight and main compression force in a rotary tablet press was characterized by the classical Kawakita equation. A load cell, situated at the exit of the tablet press chute, was also designed to measure the tablet production rate as well as the tablet weight. A novel data reconciliation strategy was proposed to reconcile the tablet weight measurement subject to the correlation between tablet weight and main compression force, in such, the imperfect tablet weight measurement can be reconciled with the much more precise main compression force measurement. Special features of the Welsch robust estimator to reject the measurement gross errors and the Kawakita model parameter estimation to monitor the material property variance were also discussed. The proposed data reconciliation strategy was first evaluated with process control open-loop and closed-loop experimental data and then integrated into the process control system in a continuous tablet manufacturing line. Specifically, the real-time reconciled tablet weight measurements were independently verified with an at-line Sotax Auto Test 4 tablet weight measurements every five minutes. Promising and reliable performance of the reconciled tablet weight measurement was demonstrated in achieving process automation and quality control of tablet weight in pilot production runs.

Obesity measured as percent body fat, relationship with body mass index, and percentile curves for Mexican pediatric population.

In Mexico, the increase in childhood obesity is alarming. Thus, improving the precision of its diagnosis is expected to impact on disease prevention. We estimated obesity prevalence by bioimpedance-based percent body fat (%BF) and body mass index (BMI) in 1061 girls and 1121 boys, from 3 to 17 years old. Multiple regressions and area under receiver operating curves (AUC) were used to determine the predictive value of BMI on %BF and percentile curves were constructed. Overall obesity prevalence estimated by %BF was 43.7%, and by BMI it was 20.1%; it means that the diagnosis by BMI underestimated around 50% of children diagnosed with obesity by %BF (≥30% for girls, ≥25% for boys). The fat mass excess is further underestimated in boys than in girls when using the standard BMI classification. The relationship between %BF and BMI was strong in school children and adolescents (all cases R2>0.70), but not in preschool children (girls R2 = 0.57, boys R2 = 0.23). AUCs showed greater discriminative power of BMI to detect %BF obesity in school children and adolescents (all cases AUC≥0.90) than in preschool children (girls AUC = 0.86; boys AUC = 0.70). Growth percentile charts showed that girls aged 9-17 years and boys aged 8-17 years presented fat excess from the 50th percentile and above. We suggested to change the BMI cut-off for them, considering values at the 75th percentile as overweight, and values at the 85th percentile as obesity, as previously recommended for Mexican children. Improving obesity diagnosis will allow greater efficiency when searching for comorbidities in clinical practice.

Phenotypic variability associated to genomic changes in the main vector of Chagas disease in the southern cone of South America.

This study shows for the first time, the relationship between chromosomic and meristic quantitative characters of Triatoma infestans, the main vector of Chagas disease in the southern cone of South America. The antennal phenotype of 225 adults from five countries and three cytotypes, were analyzed using univariate and multivariate techniques. The study found a clear association between cytotypes and antennal phenotypes. The complexity of the antennal sensilla pattern was higher in the non-Andean cytotype, showing more chemoreceptors usually linked to sexual behaviour, host finding and flight. The phenetic differences were more notorious on females than on males. Changes in the sexual dimorphism were detected, being the differences most notorious in the non-Andean cytotype. Similitude of the geographic populations using the antennal phenotype coincides with environmental gradient of the area, showing a close association between the physical features of the living zones and quantitative traits of the vectors. The epidemiological implications of the phenetic differences observed in the study are discussed.

Robust state estimation of feeding-blending systems in continuous pharmaceutical manufacturing.

State estimation is a fundamental part of monitoring, control, and real-time optimization in continuous pharmaceutical manufacturing. For nonlinear dynamic systems with hard constraints, moving horizon estimation (MHE) can estimate the current state by solving a well-defined optimization problem where process complexities are explicitly considered as constraints. Traditional MHE techniques assume random measurement noise governed by some normal distributions. However, state estimates can be unreliable if noise is not normally distributed or measurements are contaminated with gross or systematic errors. To improve the accuracy and robustness of state estimation, we incorporate robust estimators within the standard MHE skeleton, leading to an extended MHE framework. The proposed MHE approach is implemented on two pharmaceutical continuous feeding-blending system (FBS) configurations which include loss-in-weight (LIW) feeders and continuous blenders. Numerical results show that our MHE approach is robust to gross errors and can provide reliable state estimates when measurements are contaminated with outliers and drifts. Moreover, the efficient solution of the MHE realized in this work, suggests feasible application of on-line state estimation on more complex continuous pharmaceutical processes.

Sensor Network for Continuous Tablet Manufacturing.

The progress in the mechanistic understanding of the unit operations and the availability of multiple sensor technologies enable the inline implementation of data reconciliation and gross error detection methods in continuous pharmaceutical manufacturing. In this work, we demonstrate the benefits of accurate real-time monitoring of the process state in a continuous tableting process, with case studies representative of common situations in pilot-plant or manufacturing line implementation.

Association between antennal phenotype, wing polymorphism and sex in the genus Mepraia (Reduviidae: Triatominae).

Mepraia spinolai and Mepraia gajardoi (Hemiptera, Reduviidae) are only found in the arid regions of northern Chile. Mepraia is the only genus of Triatominae with marked wing polymorphism. Females of both species are micropterous, males of M. spinolai may be micropterous, brachypterous or macropterous, while males of M. gajardoi are always brachypterous. Because of this wing polymorphism, Mepraia can be used as a model to analyze morphological adaptations related to the flying activity and evolutionary relationships in the Triatominae. The study presented here analyses the antennal phenotype of the Mepraia species and carries out a comparison with the two species of Triatoma included in the spinolai complex (Triatoma eratyrusiformis and Triatoma breyeri). The analysis of the antennal phenotype of Mepraia showed a marked intraspecific phenotypic variability related with sex and wing condition. The number and length of multiporous trichoid sensilla (TH) on the pedicel are significantly higher and longer in winged males and are strongly reduced in females. The great length of the TH sensillum is an infrequent characteristic within Triatominae. The results show that phenetic distances between sexes are greater than between the two species. Similarity between the Mepraia species and T. eratyrusiformis was found as they all show long bristles (BR) and TH and two sized basiconic receptors (BA), a pattern that have not been observed in other species of Triatominae. These characters are not present in T. breyeri.