Design of sustainable reactor based on key performance indicators

The design of chemical reactors has been largely considered primarily related to techno-economic evaluations. However, the recent need for sustainable solutions and processes has promoted the inclusion of environmental and safety parameters to identify the most suitable solution. In this sense, an innovative procedure has been developed in this work to identify and design a reactive section in chemical processes. To this aim, different key performance indicators have been defined and quantified for each domain considered within the analysis, namely technological, economic, environmental, and safety domains. In addition, the safety aspects have been quantified by integrating Semenov's theory and Varma, Morbidelli and Wu's theory. The validity and potentiality of the proposed procedure have been tested and shown by applying it to a case study representative for the scale-up of pharmaceutical processes: the industrial synthesis of a Vitamin A intermediate. A preliminary design has been performed for different configurations based on apparent kinetics determined from experimental data and ab initio coefficients available in the current literature. Among the analysed solutions, a single reactor with a volume of 15.90 m3 has been indicated as the most suitable for the process requirements regarding overall sustainability. Hence, the developed procedure can be intended as a powerful tool for screening among available configurations, enabling a more informed decision by simplifying and optimising the scale-up and the detailed design

Hydrogeology and geochemistry of the sulfur karst springs at Santa Cesarea Terme (Apulia, southern Italy)

This work describes the geochemical and hydrogeological characteristics of Santa Cesarea Terme, an active sulfuric acid speleogenetic system located along the Adriatic coastline (Apulia, southern Italy). It represents a very peculiar site, where rising thermal and acidic waters mix with seawater creating undersaturated solutions with respect to CaCO3, able to dissolve and corrode limestone and create caves. The Santa Cesarea Terme system is composed of four caves: Fetida, Sulfurea, Gattulla, and Solfatara. Hypogene morphologies and abundant deposits of native sulfur (especially in Gattulla Cave) and sulfate minerals are present in these caves. Fetida and Gattulla caves were investigated primarily because they are easily accessible throughout the whole year through artificial entrances, the other caves being reachable only from the sea. Geochemical analysis of water, monitoring of cave atmosphere, and measurement of the stable isotopes of S, O, and H helped to identify the main processes occurring in this complex cave system. In particular, changes in Ba2+ and Sr2+ concentration allowed for the identification of two main domains of influence, characterized by marine and rising acidic waters

Born to be exported: COOH-terminal nuclear export signals of different strength ensure cytoplasmic accumulation of nucleophosmin leukemic mutants

Creation of a nuclear export signal (NES) motif and loss of tryptophans (W) 288 and 290 (or 290 only) at the COOH terminus of nucleophosmin (NPM) are both crucial for NPM aberrant cytoplasmic accumulation in acute myelogenous leukemia (AML) carrying NPM1 mutations. Hereby, we clarify how these COOH-terminal alterations functionally cooperate to delocalize NPM to the cytoplasm. Using a Rev(1.4)-based shuttling assay, we measured the nuclear export efficiency of six different COOH-terminal NES motifs identified in NPM mutants and found significant strength variability, the strongest NES motifs being associated with NPM mutants retaining W288. When artificially coupled with a weak NES, W288-retaining NPM mutants are not exported efficiently into cytoplasm because the force (W288) driving the mutants toward the nucleolus overwhelms the force (NES) exporting the mutants into cytoplasm. We then used this functional assay to study the physiologic NH2-terminal NES motifs of wild-type NPM and found that they are weak, which explains the prominent nucleolar localization of wild-type NPM. Thus, the opposing balance of forces (tryptophans and NES) seems to determine the subcellular localization of NPM. The fact that W288-retaining mutants always combine with the strongest NES reveals mutational selective pressure toward efficient export into cytoplasm, pointing to this event as critical for leukemogenesis

Baseline chronic comorbidity and mortality in laboratory-confirmed COVID-19 cases: Results from the PRECOVID study in Spain

We aimed to analyze baseline socio-demographic and clinical factors associated with an increased likelihood of mortality in men and women with coronavirus disease (COVID-19). We conducted a retrospective cohort study (PRECOVID Study) on all 4412 individuals with laboratory-confirmed COVID-19 in Aragon, Spain, and followed them for at least 30 days from cohort entry. We described the socio-demographic and clinical characteristics of all patients of the cohort. Age-adjusted logistic regressions models were performed to analyze the likelihood of mortality based on demographic and clinical variables. All analyses were stratified by sex. Old age, specific diseases such as diabetes, acute myocardial infarction, or congestive heart failure, and dispensation of drugs like vasodilators, antipsychotics, and potassium-sparing agents were associated with an increased likelihood of mortality. Our findings suggest that specific comorbidities, mainly of cardiovascular nature, and medications at the time of infection could explain around one quarter of the mortality in COVID-19 disease, and that women and men probably share similar but not identical risk factors. Nonetheless, the great part of mortality seems to be explained by other patient-and/or health-system-related factors. More research is needed in this field to provide the necessary evidence for the development of early identification strategies for patients at higher risk of adverse outcomes

Prevalence, Outcome, and Prevention of Congenital Cytomegalovirus Infection in Neonates Born to Women with Preconception Immunity (CHILd Study)

Background: Human cytomegalovirus (HCMV) is the leading infectious cause of congenital disabilities. We designed a prospective study to investigate the rate, outcome, and risk factors of congenital CMV (cCMV) infection in neonates born to immune women, and the potential need and effectiveness of hygiene recommendations in this population. Methods: The study was composed of 2 sequential parts: an epidemiology (part 1) and a prevention (part 2) study. Performance of part 2 depended upon a cCMV rate >0.4%. Women enrolled in part 1 did not receive hygiene recommendations. Newborns were screened by HCMV DNA testing in saliva and cCMV was confirmed by urine testing. Results: Saliva swabs were positive for HCMV DNA in 45/9661 newborns and cCMV was confirmed in 18 cases. The rate of cCMV was. 19% (95% confidence interval [CI]:. 11-.29%), and 3 out of 18 infants with cCMV had symptoms of CMV at birth. Age, nationality, occupation, and contact with children were similar between mothers of infected and noninfected newborns. Twin pregnancy (odds ratio [OR]: 7.2; 95% CI: 1.7-32.2; P =. 037) and maternal medical conditions (OR: 3.9; 95% CI: 1.5-10.1; P =. 003) appeared associated with cCMV. Given the rate of cCMV was lower than expected, the prevention part of the study was cancelled. Conclusions: Newborns from women with preconception immunity have a low rate of cCMV, which appears to be mostly due to reactivation of the latent virus. Therefore, serological screening in childbearing age would be pivotal to identify HCMV-seropositive women, whose newborns have a low risk of cCMV. Clinical trials registration: www.clinicaltrials.gov (NCT03973359)

Consensus protocol for EEG and amplitude-integrated EEG assessment and monitoring in neonates

The aim of this work is to establish inclusive guidelines on electroencephalography (EEG) applicable to all neonatal intensive care units (NICUs). Guidelines on ideal EEG monitoring for neonates are available, but there are significant barriers to their implementation in many centres around the world. These include barriers due to limited resources regarding the availability of equipment and technical and interpretive round-the-clock personnel. On the other hand, despite its limitations, amplitude-integrated EEG (aEEG) (previously called Cerebral Function Monitor [CFM]) is a common alternative used in NICUs. The Italian Neonatal Seizure Collaborative Network (INNESCO), working with all national scientific societies interested in the field of neonatal clinical neurophysiology, performed a systematic literature review and promoted interdisciplinary discussions among experts (neonatologists, paediatric neurologists, neurophysiologists, technicians) between 2017 and 2020 with the aim of elaborating shared recommendations. A consensus statement on videoEEG (vEEG) and aEEG for the principal neonatal indications was established. The authors propose a flexible frame of recommendations based on the complementary use of vEEG and aEEG applicable to the various neonatal units with different levels of complexity according to local resources and specific patient features. Suggestions for promoting cooperation between neonatologists, paediatric neurologists, and neurophysiologists, organisational restructuring, and teleneurophysiology implementation are provided

How do cardiologists select patients for dual antiplatelet therapy continuation beyond 1 year after a myocardial infarction? Insights from the EYESHOT Post-MI Study

Background: Current guidelines suggest to consider dual antiplatelet therapy (DAPT) continuation for longer than 12 months in selected patients with myocardial infarction (MI). Hypothesis: We sought to assess the criteria used by cardiologists in daily practice to select patients with a history of MI eligible for DAPT continuation beyond 1 year. Methods: We analyzed data from the EYESHOT Post-MI, a prospective, observational, nationwide study aimed to evaluate the management of patients presenting to cardiologists 1 to 3 years from the last MI event. Results: Out of the 1633 post-MI patients enrolled in the study between March and December 2017, 557 (34.1%) were on DAPT at the time of enrolment, and 450 (27.6%) were prescribed DAPT after cardiologist assessment. At multivariate analyses, a percutaneous coronary intervention (PCI) with multiple stents and the presence of peripheral artery disease (PAD) resulted as independent predictors of DAPT continuation, while atrial fibrillation was the only independent predictor of DAPT interruption for patients both at the second and the third year from MI at enrolment and the time of discharge/end of the visit. Conclusions: Risk scores recommended by current guidelines for guiding decisions on DAPT duration are underused and misused in clinical practice. A PCI with multiple stents and a history of PAD resulted as the clinical variables more frequently associated with DAPT continuation beyond 1 year from the index MI

Extremely Low Temperatures for the Synthesis of Ethylene Oxide

The partial oxidation of ethylene in a methane atmosphere by pure oxygen is the most important industrial process for the synthesis of ethylene oxide. However, due to the high reactivity and exothermicity of the reaction system, the overall production is limited by kinetic and safety issues. The shift toward mild operative conditions can support the management of undesirable side reactions, enhancing the performance of the whole process. In the future, the direct use of liquefied ethylene and oxygen-enriched air, a low-cost waste in membrane-based nitrogen production, can provide convenient sources for heat removal as well as promote the use of innovative and more sustainable solutions. This work is focused on the experimental and numerical characterization of the oxidation of ethylene/methane/nitrogen/ ethylene/methane/nitrogen/ oxygen mixtures at different operative conditions, including extremely low temperatures, and oxidant compositions. To this aim, the laminar burning velocity and flammability limits were first measured utilizing the heat flux burner and compared with detailed kinetic mechanisms and experiments retrieved from the current literature. The reported data were adopted to identify the operational limits for innovative processes, paving the way to unlocking the potential of innovative chemistry at extreme conditions. Eventually, key performance indicators accounting for kinetic and safety aspects were defined to identify the most sustainable and convenient conditions