Development of a Measurement System Using Infrared Spectroscopy-Attenuated Total Reflectance, Principal Component Analysis and Artificial Intelligence for the Safe Quantification of the Nucleating Agent Sorbitol in Food Packaging.

Sorbitol derivatives and other additives are commonly used in various products, such as packaging or food packaging, to improve their mechanical, physical, and optical properties. To accurately and precisely evaluate the efficacy of adding sorbitol-type nucleating agents to these articles, their quantitative determination is essential. This study systematically investigated the quantification of sorbitol-type nucleating agents in food packaging made from impact copolymers of polypropylene (PP) and polyethylene (PE) using attenuated total reflectance infrared spectroscopy (ATR-FTIR) together with analysis of principal components (PCA) and machine learning algorithms. The absorption spectra revealed characteristic bands corresponding to the C-O-C bond and hydroxyl groups attached to the cyclohexane ring of the molecular structure of sorbitol, providing crucial information for identifying and quantifying sorbitol derivatives. PCA analysis showed that with the selected FTIR spectrum range and only the first two components, 99.5% of the variance could be explained. The resulting score plot showed a clear pattern distinguishing different concentrations of the nucleating agent, affirming the predictability of concentrations based on an impact copolymer. The study then employed machine learning algorithms (NN, SVR) to establish prediction models, evaluating their quality using metrics such as RMSE, R2, and RMSECV. Hyperparameter optimization was performed, and SVR showed superior performance, achieving near-perfect predictions (R2 = 0.9999) with an RMSE of 0.100 for both calibration and prediction. The chosen SVR model features two hidden layers with 15 neurons each and uses the Adam algorithm, balanced precision, and computational efficiency. The innovative ATR-FTIR coupled SVR model presented a novel and rapid approach to accurately quantify sorbitol-type nucleating agents in polymer production processes for polymer research and in the analysis of nucleating agent derivatives. The analytical performance of this method surpassed traditional methods (PCR, NN).

Retrieval of HCV patients lost to follow-up as a strategy for Hepatitis C Microelimination: results of a Brazilian multicentre study.

BACKGROUND: Several HCV patients in Brazil were lost to follow-up (LTFU) in the last two decades before achievement of sustained virological response (SVR). Strategies to recall those diagnosed but untreated patients have been used elsewhere with different success rates. AIM: To identify and retrieve LTFU patients in order to offer them the treatment with the current highly effective direct acting antiviral agents (DAAs). METHODS: Registries ofall HCV patients from three large reference centers in Brazil were retrospectively reviewed to identify those with no registry of SVR. Reasons for non-achievement of SVR were elicited in HCV-RNA + patients. All patients who were not treated or cured were contacted to offer the therapy with DAAs. RESULTS: 10,289 HCV patients (50% males, mean age 52 ± 11 years) were identified. Only 4,293 (41.7%) had been successfully treated previously. From the remaining 5,996 most were LTFU (59%), were not treated for other reasons (14.7%) or were non-responders (26.3%). After revision of the charts 3,559 were considered eligible to be retrieved. The callback success of phone calls was 18%, 13% to cellphone messages (SMS or WhatsApp) and 7% to regular mail. Five-hundred sixty patients had been already treatedor were on treatment and 234 were reported to be dead or transplanted. Finally, 201 had made an appointment and initiated antiviral treatment. CONCLUSION: Even considering the low callback rate, retrieval of LTFU patients was shown to be an important strategy forhepatitis C micro-elimination in Brazil.

Machine learning based forecast for the prediction of inpatient bed demand.

BACKGROUND: Overcrowding is a serious problem that impacts the ability to provide optimal level of care in a timely manner. High patient volume is known to increase the boarding time at the emergency department (ED), as well as at post-anesthesia care unit (PACU). Furthermore, the same high volume increases inpatient bed transfer times, which causes delays in elective surgeries, increases the probability of near misses, patient safety incidents, and adverse events. OBJECTIVE: The purpose of this study is to develop a Machine Learning (ML) based strategy to predict weekly forecasts of the inpatient bed demand in order to assist the resource planning for the ED and PACU, resulting in a more efficient utilization. METHODS: The data utilized included all adult inpatient encounters at Geisinger Medical Center (GMC) for the last 5 years. The variables considered were class of inpatient encounter, observation, or surgical overnight recovery (SORU) at the time of their discharge. The ML based strategy is built using the K-means clustering method and the Support Vector Machine Regression technique (K-SVR). RESULTS: The performance obtained by the K-SVR strategy in the retrospective cohort amounts to a mean absolute percentage error (MAPE) that ranges between 0.49 and 4.10% based on the test period. Additionally, results present a reduced variability, which translates into more stable forecasting results. CONCLUSIONS: The results from this study demonstrate the capacity of ML techniques to forecast inpatient bed demand, particularly using K-SVR. It is expected that the implementation of this model in the workflow of bed capacity management will create efficiencies, which will translate in a more reliable, inexpensive and timely care for patients.

Aging impairs fibrosis-4 index after sustained virologic response by direct-acting antivirals in chronic hepatitis C infection.

INTRODUCTION AND OBJECTIVES: Sustained virologic response (SVR) is achieved in most cases of C-type liver disease after direct-acting antiviral (DAA) therapy. Although liver fibrosis improves, the degree of improvement is different. This study aimed to analyze the factors involved in improving liver fibrosis using the fibrosis 4 (FIB-4) index. MATERIAL AND METHODS: Patients were monitored for >3 years after SVR. At the start of therapy (SOT), liver fibrosis was categorized as either mild (<1.45 n = 28), moderate (1.45-3.25 n = 139), or advanced (>3.25 n = 236) based on the FIB-4 index. The FIB-4 index in the advanced group decreased significantly compared to that of the other two, so we selected the advanced group as the analysis target. SOT and end of therapy (EOT) factors that contributed to the FIB-4 index ≤3.25 at 3 years after therapy were examined using a multivariate analysis. RESULTS: Among the SOT factors, age (<72 years old), absence of liver cirrhosis (LC), alanine transferase (ALT) (≥50 U/L), platelet (PLT) (≥10.2 × 104/mm3), and total bilirubin (T.Bil) (<0.8 mg/dl) were the significant factors contributing to the improvement of the FIB-4 index. Among the EOT factors, age (<72 years), PLT (≥12.0 × 104/mm3), and hemoglobin (Hb) (≥12.1 g/dl) were the significant factors contributing to the improvement of FIB-4 index. CONCLUSIONS: Factors involved in the improvement of liver fibrosis after SVR were young age, absence of LC, low T.Bil., high ALT, high PLT, and high Hb levels. The levels of T.Bil, PLT, and Hb were considered to be related to portal hypertension. Aging strongly impaired the improvement in liver fibrosis.

Molecular typing of Campylobacter jejuni strains: comparison among four different techniques.

This study compared the ability of pulsed-field gel electrophoresis (PFGE), flaA small variable region (SVR) sequencing, analysis of the clustered regularly interspaced short palindromic repeats locus by high resolution melting analysis (CRISPR-HRMA), and multilocus sequence typing (MLST) for typing 111 Campylobacter jejuni strains isolated from diverse sources during 20 years in Brazil. For this, we used previous results obtained by PFGE and flaA-SVR sequencing from our research group and performed CRISPR-HRMA and MLST typing for the first time. Furthermore, the discrimination index (DI) of each method was accessed. The DI for PFGE, flaA-SVR sequencing, CRISPR-HRMA, and MLST was 0.980, 0.932, 0.868, and 0.931, respectively. By PFGE and flaA-SVR sequencing, some strains from clinical and non-clinical sources and from humans and animals presented ≥ 80% similarity. Similarly, some strains from different origins presented the same ST and CRISPR-HRMA types. In conclusion, despite the different DI values, all assays provided the same epidemiological information suggesting that a potential transmission may have occurred between C. jejuni from clinical and non-clinical sources and from animals and humans in Brazil. Furthermore it was demonstrated the suitability of PFGE that should be used preferably together with MLST and/or flaA-SVR sequencing for typing C. jejuni strains.

Early Successes in an Open Access, Provincially Funded Hepatitis C Treatment Program in Prince Edward Island.

INTRODUCTION: The availability of curative hepatitis C therapies has created an opportunity to improve delivery and access. Local providers, government, industry, and community groups in Prince Edward Island developed an innovative province-wide care model. Our goal was to describe the first year of program implementation. MATERIAL AND METHODS: Using a community based prospective observational study design, all chronic hepatitis C referrals received from April 2015 to April 2016 were recorded in a database. Primary analysis assessed the time from referral to assessment/treatment, as well as the number of referrals, assessments, and treatment initiations. Secondary objectives included: 1) Treatment effectiveness using intention-to-treat analysis; and 2) Patient treatment experience assessed using demographics, adverse events, and medication adherence. RESULTS: During the study period 242 referrals were received, 123 patients were seen for intake assessments, and 93 initiated direct-acting antiviral therapy based on medical need. This is compared to 4 treatment initiations in the previous 2 years. The median time from assessment to treatment initiation was 3 weeks. Eighty-two of 84 (97.6%, 95% CI 91.7 - 99.7%) patients for whom outcome data were available achieved sustained virologic response at 12 weeks post-treatment; 1 was lost to follow-up and 1 died from an unrelated event. In the voluntary registry, 39.7% of patients reported missed treatment doses. CONCLUSION: In conclusion, results from the first 12 months of this multi-phase hepatitis C elimination strategy demonstrate improved access to treatment, and high rates of safe engagement and cure for patients living with chronic hepatitis C genotype 1 infections.

Curing Chronic Hepatitis C: A Cost Comparison of the Combination Simeprevir Plus Sofosbuvir vs. Protease-Inhibitor-Based Triple Therapy

ABSTRACT Introduction. Interferon-free, multi-direct acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection is highly effective and well tolerated, but costly. To gain perspective on the evolving economics of HCV therapy, we compared the cost per cure of a multi-DAA regimen with the prior standard of triple therapy. Material and methods. Patients infected with HCV genotype 1 who were treated through the University of Colorado Hepatology Clinic between May 2011 and December 2014 comprised the study population. The multi-DAA regimen of simeprevir plus sofosbuvir (SMV/SOF) was compared to the triple therapy regimen consisting of peginterferon and ribavirin, with either boceprevir or telaprevir (TT). Sustained-virologic response (SVR) rates, total costs per treatment and adverse events were recorded. Total cost per SVR were compared for the two treatments, controlling for patient demographics and clinical characteristics. Results. One hundred eighty-three patients received SMV/SOF (n = 70) or TT (n = 113). Patients receiving SMV/SOF were older, more treatment experienced, and had a higher stage of fibrosis. SVRs were 86% and 59%, average total costs per patient were $152,775 and $95,943, and average total costs per SVR were $178,237 vs. $161,813.49 for SMV/SOF and TT groups, respectively. Medication costs accounted for 98% of SMV/SOF and 85% of TT treatment costs. Conclusion. The high cure rate of multi-DAA treatment of HCV is offset by the high costs of the DAAs, such that the cost per cure from TT to multi-DAA therapy has been relatively constant. In order to cure more patients, either additional financial resources will need to be allocated to the treatment of HCV or drug costs will need to be reduced.

Assessment of IL-28: rs12979860 and rs8099917 Polymorphisms in a Cohort of Cuban Chronic HCV Genotype 1b Patients.

Hepatitis C virus (HCV) is a significant global public health problem with >185 million infections worldwide. A series of genome-wide association studies (GWAS) has identified IL-28B polymorphisms as a predictor of sustained virologic response (SVR), as well as spontaneous clearance in chronic HCV genotype 1 patients. The objective of this work was to evaluate the prevalence of IL-28B rs12979860 and rs8099917 polymorphisms in Cuban chronic HCV patients. The study cohort included 73 chronic HCV patients treated with concomitant administration of CIGB-230 and nonpegylated IFN-α plus ribavirin (non-pegIFN-α/R) antiviral therapy. The genotype distribution of IL-28B rs12979860CC, -CT, and -TT was 29, 41, and 30%, respectively, and the distribution for rs8099917TT, -TG, and -GG was 63, 31, and 5%, respectively. The allele frequencies for rs12979860C and -T alleles were 51 and 49%, respectively, and for rs8099917G and -T alleles, the values were 21 and 79%, respectively. SVR rates were 55, 42, and 35% for rs12979860CC, -CT, and -TT, respectively, and 52, 30, and 25% for rs8099917TT, -GT, and -GG, respectively. The combined assessment of both single nucleotide polymorphisms (SNPs) resulted in 3 major genotypes (rs12979860CC/rs8099917TT, rs12979860CT/rs8099917TT, and rs12979860CT/rs8099917GG) with a frequency of 30.1, 21.9, and 20.5%, respectively. In patients with heterozygous variant rs12979860CT, the additional genotyping of rs8099917 contributed to increase the SVR rate. It is concluded that in Cuban HCV-infected patients, the responder homogeneous variant rs8099917TT is the most frequent genotype. The simultaneous genotyping of 2 IL-28B SNPs could improve the prediction of SVR contributing to better therapeutic decisions and treatment management.

Changes in cardiac function and cerebral blood flow in relation to peri/intraventricular hemorrhage in extremely preterm infants.

OBJECTIVE: To investigate whether changes in cardiac function and cerebral blood flow (CBF) precede the occurrence of peri/intraventricular hemorrhage (P/IVH) in extremely preterm infants. STUDY DESIGN: In this prospective observational study, 22 preterm infants (gestational age 25.9 ± 1.2 weeks; range 23-27 weeks) were monitored between 4 and 76 hours after birth. Cardiac function and changes in CBF and P/IVH were assessed by ultrasound every 12 hours. Changes in CBF were also followed by continuous monitoring of cerebral regional oxygen saturation (rSO2) and by calculating cerebral fractional oxygen extraction. RESULTS: Five patients developed P/IVH (1 patient grade II and 4 patients grade IV). Whereas measures of cardiac function and CBF remained unchanged in neonates without P/IVH, patients with P/IVH tended to have lower left ventricular output and had lower left ventricle stroke volume and cerebral rSO2 and higher cerebral fractional oxygen extraction during the first 12 hours of the study. By 28 hours, these variables were similar in the 2 groups and myocardial performance index was lower and middle cerebral artery mean flow velocity higher in the P/IVH group. P/IVH was detected after these changes occurred. CONCLUSIONS: Cardiac function and CBF remain stable in very preterm neonates who do not develop P/IVH during the first 3 postnatal days. In very preterm neonates developing P/IVH during this period, lower systemic perfusion and CBF followed by an increase in these variables precede the development of P/IVH. Monitoring cardiac function and cerebral rSO2 may identify infants at higher risk for developing P/IVH before the bleeding occurs.

Variation in feeding practices following the Norwood procedure.

OBJECTIVES: To assess variation in feeding practice at hospital discharge after the Norwood procedure, factors associated with tube feeding, and associations among site, feeding mode, and growth before stage II. STUDY DESIGN: From May 2005 to July 2008, 555 subjects from 15 centers were enrolled in the Pediatric Heart Network Single Ventricle Reconstruction Trial; 432 survivors with feeding data at hospital discharge after the Norwood procedure were analyzed. RESULTS: Demographic and clinical variables were compared among 4 feeding modes: oral only (n = 140), oral/tube (n = 195), nasogastric tube (N-tube) only (n = 40), and gastrostomy tube (G-tube) only (n = 57). There was significant variation in feeding mode among sites (oral only 0%-81% and G-tube only 0%-56%, P < .01). After adjusting for site, multivariable modeling showed G-tube feeding at discharge was associated with longer hospitalization, and N-tube feeding was associated with greater number of discharge medications (R(2) = 0.65, P < .01). After adjusting for site, mean pre-stage II weight-for-age z-score was significantly higher in the oral-only group (-1.4) vs the N-tube-only (-2.2) and G-tube-only (-2.1) groups (P = .04 and .02, respectively). CONCLUSIONS: Feeding mode at hospital discharge after the Norwood procedure varied among sites. Prolonged hospitalization and greater number of medications at the time of discharge were associated with tube feeding. Infants exclusively fed orally had a higher weight-for-age z score pre-stage II than those fed exclusively by tube. Exploring strategies to prevent morbidities and promote oral feeding in this highest risk population is warranted.

Dual role of IL-12 in the therapeutic efficacy or failure during combined PEG-Interferon-α2A and ribavirin therapy in patients with chronic hepatitis C.

Several efforts have been made to establish novel biomarkers with relevant predictive values to monitor HCV-infected patients under pegilated Interferon-α2A-(PEG-IFN-α2A)/ribavirin therapy. The aim of this study was to monitor the kinetics of HCV viral load, serum levels of pro-inflammatory/regulatory cytokines and leukocyte activation status before and after PEG-IFN-α2A/ribavirin therapy in 52 volunteers, including 12 chronic HCV patients and 40 controls. The HCV viral load, serum levels of cytokines (IL-8/IL-6/TNF-α/IL-12/IFN-γ/IL-4/IL-10) and the phenotype of peripheral blood leukocytes were evaluated before and after 4, 12 and 24 weeks following the PEG-IFN-α2A/ribavirin therapy. Our results demonstrated that sustained virological response-(SVR) is associated with early decrease in the viral load after 4 weeks of treatment. The presence of a modulated pro-inflammatory profile at baseline favors SVR, whereas a strong inflammatory response at baseline predisposes to therapeutic failure. Furthermore, a time-dependent increase on serum IL-12 levels in patients under treatment is critical to support the SVR, while the early predominance of IL-10 correlates to late virological relapse. On the other hand, a broad but unguided "cytokine storm" is observed in the non-responder HCV patients after 12 weeks of treatment. Corroborating these findings, monocyte/lymphocyte activation at baseline is associated with the non-responders to therapy whereas high CD8(+) T-cell numbers associate with SVR. All in all, these data suggest that the baseline pattern of serum pro-inflammatory/regulatory cytokines and the immunological activation status of chronic HCV patients undergoing PEG-IFN-α2A/ribavirin therapy are closely related with the therapeutic response.

Aplicación de los instrumentos de reincidencia en violenciaHCR-20 y SVR-20 en dos grupos de delincuentes colombianos / Application of the violence recidivism instruments HCR-20 and SVR-20 in two groups of Colombian offenders / Aplicação dos instrumentos de reincidência na violênciaHCR-20 e SVR-20 em dois grupos criminosos colombianos

Esta investigación, de tipo exploratorio, cuenta con un diseño no experimental y transversal o transeccional; tuvo por objeto determinar si los instrumentos de evaluación psicológica forense HCR-20 y SVR-20 discriminan entre un grupo de reincidentes en delitos de acceso carnal violento y un grupo de sujetos judicializados por delitos menores. Hubo presencia de los indicadores, tanto del HCR-20 como del SVR-20, en los grupos. Se encontraron diferencias significativas en los puntajes de los grupos para el SVR-20, pero no para el HCR-20. Finalmente, se observaron nuevos factores de riesgo, que podrían incluirse en instrumentos forenses

This research of exploratory nature, with its non-experimental and transversal or trans-sectional design was aimed at determining if the forensic and psychological assessment instruments known as HCR-20 (Historical Clinical Risk) and SVR-20 (Sexual Violence Risk) are discriminative at the time of evaluating a group of recidivist rapists and another group of individuals charged with minor crimes. Indicators were present for both HCR-20 and SVR-20 in he two groups. Significant indicators were found in the groups’ scores for the SVR-20, but not for the HCR-20. Finally, new risk factors that may be included in forensic instruments were observed

Esta pesquisa, exploratória, tem um projeto não-experimental e transversal ou transacional, com o objetivo de determinar se os instrumentos de avaliação psicológica forense HCR-20 e SVR-20 discriminam entre um grupo de reincidentes em crimes de estupro e um grupo de indivíduos processados por delitos menores. Havia a presença de indicadores de ambos o HCR-20 e o SVR-20 nos grupos. Encontramos diferenças significativas nas pontuações dos grupos para o SVR-20, mas não para o HCR-20. Por último, houve novos fatores de risco que poderiam ser incluídos em ferramentas forenses