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

An integrated approach to elaborate 3-D geological and geotechnical models: a case study from the Daunia Sub-Apennine (Apulia, southern Italy).

In the Daunia Sub-Apennine (Apulia, southern Italy) slope instability processes due to rainfalls and earthquakes are widespread and cause significant damage to buildings and other structures, and, in some cases, loss of life. A detailed slope stability assessment requires information on the predisposing and triggering factors, and a good knowledge of the geological and environmental conditions as well. As concerns seismic-induced landslides, conventional methods used for slope stability analysis can be divided in: i) force-based pseudo-static methods, ii) displacement-based methods, and iii) stress-strain methods. Detailed representations of geological and geotechnical units as well as static and dynamic geotechnical characterization of materials have to be considered for the correct choice of the method for slope stability analysis, since these are fundamental for slope behaviour prediction and modelling. The purpose of this paper was to present a methodological approach for elaborating detailed 3-D geological and geotechnical models for areas very heterogeneous in terms of geological and soil properties. In the southern portion of the eastern Daunia Sub-Apennine, the outermost formations of the chain domain crop out. These are represented by the Cretaceous-Miocene and Pliocene wedge-top basin units, followed upwards, in the easternmost portion, by the Plio-Pleistocene foredeep units and by Quaternary filling deposits. A high susceptibility to slope failures for the area is testified by the large number of slope movements consisting in mud flows, roto-translational and composite landslides, and soil slips. Field variability of the slope movements from site to site for mechanisms, velocity, depth of rupture surfaces and volume of materials involved is due to the presence of structurally complex formations, characterised by very poor mechanical properties and high variability of their lithological and structural features. The construction of geological and geotechnical models able to represent realistic information is conditioned by the efficacy of the methods used for assessing the spatial lithofacies distribution and parametrization. The case study of Deliceto is here presented, where the 3-D geological model was built based on the results of stratigraphic correlations between core logs and 2-D geological sections. In-situ surveys were performed by means of classical geological and geomorphological methods, and continuous coring boreholes. Silty-clayey sandstone materials (Conglomerates and Sandstones of Castello Schiavo) crop out along the slopes and rest on clayey silts and marls of turbidite origin (Flysch di Faeto). The Flysch di Faeto Fm. is a structurally complex geological unit which consists of three main lithofacies: 1) silty clays; 2) silty marly clays 3) marls and shales. A series of geotechnical laboratory tests, carried out in accordance with international standards for the static and dynamic characterization of materials, made it possible to obtain a detailed 3-D geotechnical model. In particular, resonant column (RC), cyclic torsional shear (CTS) and standard and cyclic triaxial (TXC) tests were performed on the silty clayey geotechnical unit of the Flysch di Faeto Fm., because it is highly susceptible to geotechnical fatigue resulting from cyclic stresses. The results of the laboratory tests confirmed a variable post-cyclic degradation in the range 40-80% and 12-36%, respectively for the secant shear modulus (G) and the undrained cohesion (cu) associated with an increase between 2.92% and 19.90% for the damping ratio (D), demonstrating the heterogeneity of the material in terms of geological and geotechnical characteristics

Proteasome inhibitors as a possible therapy for SARS-CoV-2

The COVID-19 global pandemic is caused by SARS-CoV-2, and represents an urgent medical and social issue. Unfortunately, there is still not a single proven effective drug available, and therefore, current therapeutic guidelines recommend supportive care including oxygen administration and treatment with antibiotics. Recently, patients have been also treated with off-label therapies which comprise antiretrovirals, anti-inflammatory compounds, antiparasitic agents and plasma from convalescent patients, all with controversial results. The ubiquitin–proteasome system (UPS) is important for the maintenance of cellular homeostasis, and plays a pivotal role in viral replication processes. In this review, we discuss several aspects of the UPS and the effects of its inhibition with particular regard to the life cycle of the coronaviruses (CoVs). In fact, proteasome inhibition by various chemical compounds, such as MG132, epoxomycin and bortezomib, may reduce the virus entry into the eucariotic cell, the synthesis of RNA, and the subsequent protein expression necessary for CoVs. Importantly, since UPS inhibitors reduce the cytokine storm associated with various inflammatory conditions, it is reasonable to assume that they might be repurposed for SARS-CoV-2, thus providing an additional tool to counteract both virus replication as well as its most deleterious consequences triggered by abnormal immunological response

Management of chronic lymphocytic leukemia: practice guidelines from the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation.

The Italian Society of Hematology (SIE) and two affiliate societies (SIES and GITMO) commissioned a project to develop clinical practice guidelines for the treatment of chronic lymphocytic leukemia (CLL). METHODS: Key questions in the management of patients with CLL were formulated by an Advisory Committee and approved by an Expert Panel of eight senior hematologists. After a systematic review of the literature, recommendations for disease-specific and supportive therapies were formulated and graded according to the supporting evidence. Explicit consensus methods were used for providing recommendations for questions with incomplete or potentially biased evidence. RESULTS: It is recommended that therapy is commenced in patients with CLL when at least one of the following are present: B-symptoms, progressive/obstructive lymphadenopathy or organomegaly, rapid lymphocyte doubling time, anemia or thrombocytopenia (of new onset, worsening or steroid-resistant). It is recommended that patients without co-morbidity should receive fludarabine plus cyclophosphamide, whereas elderly patients with co-morbidity should receive oral chlorambucil. Younger patients with unfavorable biological risk factors should be considered for high-dose chemotherapy and autologous or allogeneic stem cell transplantation within approved clinical trials. Patients either relapsing rapidly after, or non-responsive to, first-line chlorambucil should receive fludarabine-containing regimens. Patients either relapsing soon after or not responding to fludarabine-based chemotherapy should be considered for schedules including non-cross-reactive agents, such as alemtuzumab, possibly followed by high-dose chemotherapy and autologous transplantation in the context of a clinical trial or by allogeneic stem cell transplantation. CONCLUSIONS: We describe the results of a systematic literature review and an explicit approach to consensus techniques which resulted in recommendations for the key therapeutic decisions in patients with CLL

Hydro‐stratigraphic conditions and human activity leading to development of a sinkhole cluster in a Mediterranean water ecosystem

Salento Peninsula (Apulia, southern Italy) is characterised by many active sinkholes, which represent the main geological hazard. The stretch of coastline between the village of Casalabate and Le Cesine wildlife reserve is highly affected, with a system of dunes separating the low beach from extensive wetlands, which were subject to uncontrolled urban development after reclamation. The overall morphology is characterized by flat topography, whilst from a hydrogeological standpoint, the mixing of inland freshwater with advancing brackish water favours the higher aggressivity with respect to soluble rocks, and the development of enhanced dissolution (hyperkarst). The relict landscapes within the protected areas still allow for the recognition of actively occurring sinkholes, which cause damage to houses, the road network and infrastructures. In this article the case of Aquatina di Frigole is described, where in the last 15 years numerous sinkholes have formed, with the processes still in rapid evolution. Detailed surveys allow for to identification of the mechanisms of sinkhole formation (suffusion sinkholes), the deriving cluster, and the main hydrogeological links among the different water bodies in the area. Acquatina di Frigole provides an excellent natural laboratory to observe development and evolution of sinkholes, and their relationships with the stratigraphic and hydrogeological elements

Genomic segmental duplications on the basis of the t(9;22) rearrangement in chronic myeloid leukemia

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Consensus conference on the management of tumor lysis syndrome.

Tumor lysis syndrome is a potentially life threatening complication of massive cellular lysis in cancers. Identification of high-risk patients and early recognition of the syndrome is crucial in the institution of appropriate treatments. Drugs that act on the metabolic pathway of uric acid to allantoin, like allopurinol or rasburicase, are effective for prophylaxis and treatment of tumor lysis syndrome. Sound recommendations should regulate diagnosis and drug application in the clinical setting. The current article reports the recommendations on the management of tumor lysis syndrome that were issued during a Consensus Conference project, and which were endorsed by the Italian Society of Hematology (SIE), the Italian Association of Pediatric Oncologists (AIEOP) and the Italian Society of Medical Oncology (AIOM). Current concepts on the pathophysiology, clinical features, and therapy of tumor lysis syndrome were evaluated by a Panel of 8 experts. A consensus was then developed for statements regarding key questions on tumor lysis syndrome management selected according to the criterion of relevance by group discussion. Hydration and rasburicase should be administered to adult cancer patients who are candidates for tumor-specific therapy and who carry a high risk of tumor lysis syndrome. Cancer patients with a low-risk of tumor lysis syndrome should instead receive hydration along with oral allopurinol. Hydration and rasburicase should also be administered to patients with clinical tumor lysis syndrome and to adults and high-risk children who develop laboratory tumor lysis syndrome. In conclusion, the Panel recommended rasburicase for tumor lysis syndrome prophylaxis in selected patients based on the drug efficacy profile. Methodologically rigorous studies are needed to clarify its cost-effectiveness profile

Parp inhibitors and epithelial ovarian cancer: Molecular mechanisms, clinical development and future prospective (Review)

Epithelial ovarian cancer (EOC) has a poor prog- nosis. Since the introduction of paclitaxel as antineoplastic agent >20 years ago, only a few phase III randomized trials have shown challenging data regarding different therapeutic options for facing its aggressive clinical course and granting active therapies to patients. Different studies have shown the utility of poly(ADP-ribose) polymerase (PARP) inhibitors in women with EOC with or without BRCA mutations, both germ- line and somatic. Three PARP inhibitors, olaparib, rucaparib and niraparib, have been recently approved by the Food and Drug Administration for clinical use in EOC patients, though with different clinical indications and profiles of toxicity, while two other molecules, veliparib and talazoparib, are still under clinical investigation. The aim of the present paper is to evaluate the current status of PARP inhibitors in terms of molecular activity, pharmacodynamic properties and clinical applications

Osteoporosis prevention in postmenopausal female workers : Beneficial effects of silicon dietary supplementation on oxidative status. A pilot study

In the last years, the employment of ageing women is increased, and the well-being of these workers, together with the prevention of chronic disabling diseases, is an issue of great importance. Moreover, as postmenopausal ageing is associated with the loss of bone density and consequent increased fracture risk, promoting bone health in these women could be the best strategy for avoiding osteoporotic fractures. We aimed to evaluate the effects of 3-month supplementation with a commercial antioxidant product containing Silica on oxidative status and bone markers in a sample of Italian female workers. Subjects were menopausal and osteopenic women (N=29, age 59.34\ub16.37, mean BMI 26.19\ub14.01 kg/m2). At baseline (T0) and after three-month treatment (T1) bone mineral density (BMD) was evaluated by phalangeal osteosonogrammetry. Haematological, serum biochemical parameters, reactive oxygen species (ROS), total antioxidant capacity (TAC), oxydated low-density lipoproteins (oxLDL) and urinary cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) were assessed. Parametric or non-parametric tests were performed at T0 and T1. To analyse the possible association between two variables a linear correlation test was performed. At T0, slightly high levels of ROS (86% of subjects), oxLDL (59%), Total Cholesterol (T-Chol) (90%) and LDL-Chol (59%) were observed, together with suboptimal or deficient 25-OH vitamin D (98%) concentrations. At T1, oxLDL levels and the ratio oxLDL/LDL-Chol significantly decreased (p<0.01). At T0 significant negative correlations between BMD T-score and cross-links were observed (DPD/Crea: r=-0.57, p=0.001; PYD/ Crea: r=-0.45, p=0.01). At T1, a significant reduction (p=0.03) was observed only for DPD (\u3bcg/L) but not for cross-links normalized by creatinine amounts. In conclusion 3-months Silica supplementation improves significantly oxidative status and bone resorption markers in most postmenopausal female workers, representing a complementary treatment for early phases of BMD reduction