Analysis and Multiple Steady States of an Industrial Heterogeneous Azeotropic Distillation

A study of an industrial multicomponent heterogeneous azeotropic distillation is presented. The process concerns an organic acid dehydration using an immiscible entrainer. First, a validation of the MESH and thermodynamic models through a comparison between pilot-plant experimental reconciled data and simulation results is conducted. A four-component mixture is considered for the simulation. Case studies of the boiler heat duty are automatically generated by an operating path tool. An ¥/¥ analysis is performed for the heterogeneous azeotropic pilot column and an industrial column with a decanter. Because of practical constraints, the pilot and the industrial columns do not have the same reflux policies. This leads the ¥/¥ analysis to predict multiple steady states for the industrial unit but not for the pilot column. However, multiple steady states are found by simulation both for the pilot and for the industrial unit. Multiple steady states are confirmed by simulation and experimental data for the industrial unit. Because of the positive ¥/¥ analysis, they are attributed to the phase equilibrium properties of the quaternary system. For the pilot column, multiple steady states are found by the simulation and linked to experimental observations. The multiplicity is not caused by the phase equilibrium properties; rather, it is attributed to interactions between the material and energy balances. An analysis of the simulation results helps explain the behavior of the industrial unit: the temperature of the sensitive tray gives rise to a peak in heat. This peak is located very close to the industrial temperature set point and is correlated with an impurity content minimum in the main product stream. An impurity minimum is also evidenced by the simulation for the pilot column. This complex behavior can explain observed difficulties in controlling the process at the industrial set point

Differentiating IDH-mutant astrocytomas and 1p19q-codeleted oligodendrogliomas using DSC-PWI:high performance through cerebral blood volume and percentage of signal recovery percentiles

Objective: Presurgical differentiation between astrocytomas and oligodendrogliomas remains an unresolved challenge in neuro-oncology. This research aims to provide a comprehensive understanding of each tumor’s DSC-PWI signatures, evaluate the discriminative capacity of cerebral blood volume (CBV) and percentage of signal recovery (PSR) percentile values, and explore the synergy of CBV and PSR combination for pre-surgical differentiation. Methods: Patients diagnosed with grade 2 and 3 IDH-mutant astrocytomas and IDH-mutant 1p19q-codeleted oligodendrogliomas were retrospectively retrieved (2010–2022). 3D segmentations of each tumor were conducted, and voxel-level CBV and PSR were extracted to compute mean, minimum, maximum, and percentile values. Statistical comparisons were performed using the Mann-Whitney U test and the area under the receiver operating characteristic curve (AUC-ROC). Lastly, the five most discriminative variables were combined for classification with internal cross-validation. Results: The study enrolled 52 patients (mean age 45-year-old, 28 men): 28 astrocytomas and 24 oligodendrogliomas. Oligodendrogliomas exhibited higher CBV and lower PSR than astrocytomas across all metrics (e.g., mean CBV = 2.05 and 1.55, PSR = 0.68 and 0.81 respectively). The highest AUC-ROCs and the smallest p values originated from CBV and PSR percentiles (e.g., PSRp70 AUC-ROC = 0.84 and p value = 0.0005, CBVp75 AUC-ROC = 0.8 and p value = 0.0006). The mean, minimum, and maximum values yielded lower results. Combining the best five variables (PSRp65, CBVp70, PSRp60, CBVp75, and PSRp40) achieved a mean AUC-ROC of 0.87 for differentiation. Conclusions: Oligodendrogliomas exhibit higher CBV and lower PSR than astrocytomas, traits that are emphasized when considering percentiles rather than mean or extreme values. The combination of CBV and PSR percentiles results in promising classification outcomes. Clinical relevance statement: The combination of histogram-derived percentile values of cerebral blood volume and percentage of signal recovery from DSC-PWI enhances the presurgical differentiation between astrocytomas and oligodendrogliomas, suggesting that incorporating these metrics into clinical practice could be beneficial. Key Points: • The unsupervised selection of percentile values for cerebral blood volume and percentage of signal recovery enhances presurgical differentiation of astrocytomas and oligodendrogliomas. • Oligodendrogliomas exhibit higher cerebral blood volume and lower percentage of signal recovery than astrocytomas. • Cerebral blood volume and percentage of signal recovery combined provide a broader perspective on tumor vasculature and yield promising results for this preoperative classification.</p

EDUCACIÓN SUPERIOR EN ALTERNANCIA TRANSFRONTERIZA ENTRE FRANCIA Y ESPAÑA

In this study, our aim is to prove that education alternatively stimulatesthe creation of employment and encourages innovation according to thecurrent technological revolution, according to the current necessities inthe cross-border territory. For this reason, four experiences are analyzedin this cross-border area, based on higher education in alternation to bothsides of the Pyrenees as experiences in tune with the triple helix model. The institutions of higher education involved are Universidad de Mondragon, Universidad de Vic-Universidad Central de Catalunya (Spain), la Escuela Universitaria de management de la Université de Pau (France) and École Superieure des Technologies Industrielles Avancées (ESTIA). Our findings suggest the elements that should have an alternating cross-border education model considering the common and diverging issues of the analysis of the four experiences and the relevance of using this educative innovation to improve employability and promote the market entry of the students along with the regional, social and economic development of the areas under study.En este estudio se pretende evidenciar que la educación en alternancia estimula la creación de empleo e incentiva la innovación acorde a la revolución tecnológica actual, en sintonía con las necesidades de nuestro tiempo en el territorio transfronterizo. Por este motivo se analizan 4 experiencias en la zona transfronteriza basadas en educación superior en alternancia a ambos lados de los Pirineos, como experiencias en sintonía con el modelo de la Triple Hélice. Las instituciones de educación superior implicadas en las cuatro experiencias son: Universidad de Mondragón, Universidad de Vic-Universidad Central de Catalunya (en España), la École Superieure des Technologies Industrielles Avancées (ESTIA) y la Escuela Universitaria de Management de la Université de Pau (en Francia).  Nuestros hallazgos sugieren los elementos que debería incorporar un  modelo de educación en alternancia transfronteriza, considerando los aspectos comunes y discrepantes del análisis de las 4 experiencias, y la pertinencia de utilizar esta innovación educativa para mejorar la empleabilidad y promover la incorporación de los alumnos al mercado laboral junto con el oportuno desarrollo regional, económico y social de las zonas analizadas

The systemic activin response to pancreatic cancer: implications for effective cancer cachexia therapy

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a particularly lethal malignancy partly due to frequent, severe cachexia. Serum activin correlates with cachexia and mortality, while exogenous activin causes cachexia in mice. METHODS: Isoform-specific activin expression and activities were queried in human and murine tumours and PDAC models. Activin inhibition was by administration of soluble activin type IIB receptor (ACVR2B/Fc) and by use of skeletal muscle specific dominant negative ACVR2B expressing transgenic mice. Feed-forward activin expression and muscle wasting activity were tested in vivo and in vitro on myotubes. RESULTS: Murine PDAC tumour-derived cell lines expressed activin-βA but not activin-βB. Cachexia severity increased with activin expression. Orthotopic PDAC tumours expressed activins, induced activin expression by distant organs, and produced elevated serum activins. Soluble factors from PDAC elicited activin because conditioned medium from PDAC cells induced activin expression, activation of p38 MAP kinase, and atrophy of myotubes. The activin trap ACVR2B/Fc reduced tumour growth, prevented weight loss and muscle wasting, and prolonged survival in mice with orthotopic tumours made from activin-low cell lines. ACVR2B/Fc also reduced cachexia in mice with activin-high tumours. Activin inhibition did not affect activin expression in organs. Hypermuscular mice expressing dominant negative ACVR2B in muscle were protected for weight loss but not mortality when implanted with orthotopic tumours. Human tumours displayed staining for activin, and expression of the gene encoding activin-βA (INHBA) correlated with mortality in patients with PDAC, while INHBB and other related factors did not. CONCLUSIONS: Pancreatic adenocarcinoma tumours are a source of activin and elicit a systemic activin response in hosts. Human tumours express activins and related factors, while mortality correlates with tumour activin A expression. PDAC tumours also choreograph a systemic activin response that induces organ-specific and gene-specific expression of activin isoforms and muscle wasting. Systemic blockade of activin signalling could preserve muscle and prolong survival, while skeletal muscle-specific activin blockade was only protective for weight loss. Our findings suggest the potential and need for gene-specific and organ-specific interventions. Finally, development of more effective cancer cachexia therapy might require identifying agents that effectively and/or selectively inhibit autocrine vs. paracrine activin signalling

The implications of the COVID-19 pandemic on eating disorder features and comorbid psychopathology among adolescents with anorexia nervosa and matched controls:a comparative cohort design study

PurposeTo examine implications of the COVID-19 pandemic on eating disorder (ED) features and psychopathology in female adolescents with anorexia nervosa (AN).MethodIn total 79 females with first-onset AN (aged 12-22 years) were included and were followed up across a period of 1 year. We assessed AN participants recruited pre-pandemic (n = 49) to those recruited peri-pandemic (n = 30). Pre- (n = 37) and peri-pandemic (n = 38) age-, and education-matched typically developing (TD) girls (n = 75) were used as a reference cohort. ED features and psychopathology were assessed at baseline. After 1 year of follow-up the association between pandemic timing and clinical course was assessed. Analyses of covariance were used to examine differences in ED features and psychopathology.ResultsPeri-pandemic AN participants experienced less ED symptoms at baseline compared to pre-pandemic AN participants. In particular, they were less dissatisfied with their body shape, and experienced less interpersonal insecurity. In addition, the peri-pandemic AN group met fewer DSM-IV criteria for comorbid disorders, especially anxiety disorders. In contrast, peri-pandemic AN participants had a smaller BMI increase over time. In TD girls, there were no differences at baseline in ED features and psychopathology between the pre- and peri-pandemic group.ConclusionOverall, peri-pandemic AN participants were less severely ill, compared to pre-pandemic AN participants, which may be explained by less social pressure and peer contact, and a more protective parenting style during the pandemic. Conversely, peri-pandemic AN participants had a less favorable clinical course, which may be explained by reduced access to health care facilities during the pandemic.Level of evidenceLevel III: Evidence obtained from well-designed cohort or case-control analytic studies

Patient-reported outcomes in axial spondyloarthritis and psoriatic arthritis patients treated with secukinumab for 24 months in daily clinical practice

On behalf of the EuroSpA Scientific Committee, the authors acknowledge Novartis Pharma AG for supporting the EuroSpA collaboration.Peer reviewe

Health information use by patients with systemic lupus erythematosus (SLE) pre and during the COVID-19 pandemic

Objective We conducted an international survey of patients with SLE to assess their access, preference and trust in various health information sources pre-COVID-19 and during the COVID-19 pandemic. Methods Patients with SLE were recruited from 18 observational cohorts, and patients self-reporting SLE were recruited through five advocacy organisations. Respondents completed an online survey from June 2020 to December 2021 regarding the sources of health information they accessed in the 12 months preceding (pre-11 March 2020) and during (post-11 March 2020) the pandemic. Multivariable logistic regressions assessed factors associated with accessing news and social media post-11 March 2020, and self-reporting negative impacts from health information accessed through these sources. Results Surveys were completed by 2111 respondents; 92.8% were female, 76.6% had postsecondary education, mean (SD) age was 48.8 (14.0) years. Lupus specialists and family physicians were the most preferred sources pre-11 March 2020 and post-11 March 2020, yet were accessed less frequently (specialists: 78.5% pre vs 70.2% post, difference -8.3%, 95% CI -10.2% to -6.5%; family physicians: 57.1% pre vs 50.0% post, difference -7.1%, 95% CI -9.2% to -5.0%), while news (53.2% pre vs 62.1% post, difference 8.9%, 95% CI 6.7% to 11.0%) and social media (38.2% pre vs 40.6% post, difference 2.4%, 95% CI 0.7% to 4.2%) were accessed more frequently post-11 March 2020 vs pre-11 March 2020. 17.2% of respondents reported negative impacts from information accessed through news/social media. Those outside Canada, older respondents or with postsecondary education were more likely to access news media. Those in Asia, Latin America or younger respondents were more likely to access social media. Those in Asia, older respondents, males or with postsecondary education in Canada, Asia or the USA were less likely to be negatively impacted. Conclusions Physicians, the most preferred and trusted sources, were accessed less frequently, while news and social media, less trusted sources, were accessed more frequently post-11 March 2020 vs pre-11 March 2020. Increasing accessibility to physicians, in person and virtually, may help reduce the consequences of accessing misinformation/disinformation

Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility

Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the CFH-CFHRs region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic CFH SNP (rs6677604, in intron 11, Pmeta = 6.6×10-8, OR = 1.18) and an intergenic SNP between CFHR1 and CFHR4 (rs16840639, Pmeta = 2.9×10-7, OR = 1.17) rather than to previously identified disease-associated CFH exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a ~146 kb block extending from intron 9 of CFH to downstream of CFHR1. Within this block, the deletion of CFHR3 and CFHR1 (CFHR3-1Δ), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of CFHR3-1Δ (Pmeta = 3.2×10-7, OR = 1.47) conferred a higher risk of SLE than heterozygous deletion (Pmeta = 3.5×10-4, OR = 1.14). These results suggested that the CFHR3-1Δ deletion within the SLE-associated block, but not the previously described exonic SNPs of CFH, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE

Transancestral mapping and genetic load in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10-8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.info:eu-repo/semantics/publishedVersio

Transancestral mapping and genetic load in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (B50% of these regions have multiple independent associations); these include 24 novel SLE regions (Po5 10 8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SL