Stochastic gradient approach for energy and supply optimisation in water systems management

Under conditions of water scarcity, energy saving in operation of water pumping plants and the minimisation of water deficit for users and activities are frequently contrasting requirements, which should be considered when optimising large-scale multi-reservoirs and multi-users water supply systems. Undoubtedly, a high uncertainty level in predicted water resources due to hydrologic input variability and water demand behaviour characterizes this problem. The aim of this paper is to provide an efficient decision support system considering emergency water pumping plants activation schedules. The obtained results should allow the water system’s authority to adopt a robust decision policy, minimising the risk of harmful future decisions concerning the water resource management. The model has been here developed to manage this problem, in order to reduce the damages due to shortage of water and the energy-cost requirements of pumping plants. Particularly, in optimisation, we look for optimal rules considering both historical and generated synthetic scenarios of hydrologic inputs to reservoirs. Hence, using synthetic series, we can analyse climate change impacts and optimise the activation rules considering future hydrologic occurrences. A simulation model has been coupled with an optimization module using the stochastic gradient method to get robust pumping activation thresholds. This method allows to solve complex problems, solving efficiently large size real cases due to high number of data and variables. Thresholds values are identified in terms of critical storage levels in supply-reservoirs. Application of the modelling approach has been developed on a real case study in a water-shortage prone area in south-Sardinia (Italy), characterized by Mediterranean climate and high annual variability in hydrological input to reservoirs. By applying the combined simulation procedure, a robust decision strategy in pumping activation was obtained. Developing the stochastic gradient model, a main programming supports has been built by MATLAB efficiently interfaced with CPLEX for optimisation and Excel for inputs and results representation

The close relationship between the Golgi trafficking machinery and protein glycosylation

La glicosilazione è la più comune modifica post-traduzionale delle proteine; media la loro corretta piegatura e stabilità, nonché il loro trasporto attraverso il trasporto secretorio. I cambiamenti nei glicani legati all'N e all'O sono stati associati a molteplici condizioni patologiche tra cui disturbi congeniti della glicosilazione, malattie infiammatorie e cancro. La glicosilazione della glicoproteina al Golgi coinvolge l'azione coordinata di centinaia di glicosiltransferasi e glicosidasi, che vengono mantenute nella posizione corretta attraverso il traffico di vescicole retrograde tra le cisterne di Golgi. In questa recensione, descriviamo il macchinario molecolare coinvolto nel traffico di vescicole e nel tethering presso l'apparato di Golgi e gli effetti delle mutazioni nel contesto della biosintesi dei glicani e delle malattie umane.Glycosylation is the most common post-translational modification of proteins; it mediates their correct folding and stability, as well as their transport through the secretory transport. Changes in N- and O-linked glycans have been associated with multiple pathological conditions including congenital disorders of glycosylation, inflammatory diseases and cancer. Glycoprotein glycosylation at the Golgi involves the coordinated action of hundreds of glycosyltransferases and glycosidases, which are maintained at the correct location through retrograde vesicle trafficking between Golgi cisternae. In this review, we describe the molecular machinery involved in vesicle trafficking and tethering at the Golgi apparatus and the effects of mutations in the context of glycan biosynthesis and human diseases

Oncogenic roles of GOLPH3 in the physiopathology of cancer

Golgi phosphoprotein 3 (GOLPH3), un effettore del fosfatidilinositolo 4-fosfato [PI (4) P] al Golgi, è necessaria per il mantenimento della struttura del nastro del Golgi, il traffico di vescicole e la glicosilazione del Golgi. GOLPH3 è stato convalidato come oncoproteina combinando la genomica integrativa con l'analisi clinopatologiche e funzionali. È spesso amplificato in diversi tipi di tumori solidi tra cui melanoma, cancro ai polmoni, cancro al seno, glioma e cancro del colon-retto. La sovraespressione di GOLPH3 è correlata a una prognosi infausta in più tipi di tumore, compreso il 52% dei tumori al seno e dal 41% al 53% del glioblastoma. I ruoli di GOLPH3 nella tumorigenesi possono essere correlati a diverse attività cellulari, tra cui: (i) regolazione del traffico dal Golgi alla membrana plasmatica e contributo a fenotipi secretori maligni; (ii) controllare l'internalizzazione e il riciclaggio di molecole di segnalazione chiave o aumentare la glicosilazione delle glicoproteine ​​rilevanti per il cancro; e (iii) influenzare la risposta al danno al DNA e il mantenimento della stabilità genomica. Qui riassumiamo le attuali conoscenze sui percorsi oncogeni che coinvolgono GOLPH3 nel cancro umano, l'influenza di GOLPH3 sul metabolismo del tumore e sullo stroma circostante e il suo possibile ruolo nella formazione di metastasi tumorali.Golgi phosphoprotein 3 (GOLPH3), a Phosphatidylinositol 4-Phosphate [PI(4)P] effector at the Golgi, is required for Golgi ribbon structure maintenance, vesicle trafficking and Golgi glycosylation. GOLPH3 has been validated as an oncoprotein through combining integrative genomics with clinopathological and functional analyses. It is frequently amplified in several solid tumor types including melanoma, lung cancer, breast cancer, glioma, and colorectal cancer. Overexpression of GOLPH3 correlates with poor prognosis in multiple tumor types including 52% of breast cancers and 41% to 53% of glioblastoma. Roles of GOLPH3 in tumorigenesis may correlate with several cellular activities including: (i) regulating Golgi-to-plasma membrane trafficking and contributing to malignant secretory phenotypes; (ii) controlling the internalization and recycling of key signaling molecules or increasing the glycosylation of cancer relevant glycoproteins; and (iii) influencing the DNA damage response and maintenance of genomic stability. Here we summarize current knowledge on the oncogenic pathways involving GOLPH3 in human cancer, GOLPH3 influence on tumor metabolism and surrounding stroma, and its possible role in tumor metastasis formation

A bottom-up appraisal of the technically installable capacity of biogas-based solid oxide fuel cells for self power generation in wastewater treatment plants

This paper proposes a bottom-up method to estimate the technical capacity of solid oxide fuel cells to be installed in wastewater treatment plants and valorise the biogas obtained from the sludge through an efficient conversion into electricity and heat. The methodology uses stochastic optimisation on 200 biogas profile scenarios generated from industrial data and envisages a Pareto approach for an a posteriori assessment of the optimal number of generation unit for the most representative plant configuration sizes. The method ensures that the dominant role of biogas fluctuation is included in the market potential and guarantees that the utilization factor of the modules remains higher than 70% to justify the investment costs. Results show that the market potential for solid oxide fuel cells across Europe would lead up to 1,300 MW of installed electric capacity in the niche market of wastewater treatment and could initiate a capital and fixed costs reduction which could make the technology comparable with alternative combined heat and power solutions

Epilithic diatom assemblages and environmental quality of the Su Gologone karst spring (centraleastern Sardinia, Italy)

Karst springs are considered among the most vulnerable groundwater-dependent ecosystems. Despite their ecological value and importance as strategic water sources, Mediterranean karst springs are still poorly investigated. The aim of this study was to analyse the epilithic diatom assemblages and to test their usefulness as indicators of environmental quality on the Su Gologone spring (central-eastern Sardinia, Italy), a biotope of great natural value and a precious source of drinking water. A total of 89 diatom taxa were found with 25 new records for Sardinian running waters. Species richness, Shannon-Wiener and Pielou indices showed good biotic integrity. The dominant taxa were alkaliphilous, halophobous-oligohalobous exigent, xeno-oligosaprobic and characteristic of oligotrophic waters. The eutrophication/pollution index − diatom based (EPI-D) and the Navicula Nitzschia Surirella indices indicated respectively an excellent/good biological water quality and a low physical disturbance. However, the biological and chemical oxygen demand, and the microbiological variables (E. coli, fecal and total coliforms) revealed an organic contamination of the water, although moderate. The judgment provided by the EPI-D should be verified after updating of the index. In fact, 10 taxa found in this study are not currently considered by the EPI-D method

Factors influencing delayed discharge after day-surgery laparoscopic cholecystectomy: the DeDiLaCo study protocol

OBJECTIVE: Laparoscopic cholecystectomy (LC) is the gold standard for most benign gallbladder diseases. Early discharge (<24 hours) has the same outcomes as longer (>24 hours) hospital stay. Nevertheless, the rate of delayed discharge >24 hours range from 4.6% to 37%. The primary endpoint of this Italian nationwide study is to analyze the prevalence of patients undergoing elective LC who experienced a delayed discharge >24 hours and identify potential limiting factors of early discharge. Results from these analyses will be used to select patients who can be safely discharged on the same day after surgery. Secondary endpoints will be to evaluate the patient’s quality of life (QoL), assess the direct health costs associated with late discharge, and quantify the patient’s involvement in the treatment process. PATIENTS AND METHODS: This prospective, observational study was conducted following a resident-led model and the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. All patients were treated according to the local hospital protocol and received routine care as standard therapy. RESULTS: We expected to obtain the enrollment of at least 500 patients based on an assumed difference in discharge delay between the reference and the recruitable population of 6% and the identification of factors related to discharge failure within 24 h. Early discharge after LC leads to advantages both in terms of clinical outcomes and quality of life of the patient, and it is highly effective in terms of health costs and shortening the waiting list. However, clinical reality differs from the results of randomized studies by a complex series of non-objectionable real-world data influencing treatment plans. Therefore, we expected to identify independent predictors and factors of failure of early discharge. CONCLUSIONS: Clinical reality often differs from randomized trial results. In Italy, the vast majority of delayed discharges after LC may not be related to surgery and can be prevented both with logistical reorganization and with a readjustment of the trust reimbursement policies

Short-term cardiac outcome in survivors of COVID-19: a systematic study after hospital discharge

Background: COVID-19 has caused considerable morbidity and mortality worldwide and cardiac involvement has been reported during infection. The short-term cardiac outcome in survivors of COVID-19 is not known. Objective: To examine the heart of patients who survived COVID-19 and to compare the cardiac outcome between patients who recovered from mild-to-moderate or severe illness. Methods: With use of ECG and echocardiography, we examined the heart of 105 patients who had been hospitalized with COVID-19 and were consecutively recruited after hospital discharge while attending follow-up visits. Survivors of COVID-19 were compared with 105 matched controls. We also compared the cardiac outcome and lung ultrasound scan between COVID-19 patients who had mild-to-moderate or severe illness. Results: Cardiac data were collected a median of 41\ua0days from the first detection of COVID-19. Symptoms were present in a low percentage of patients. In comparison with matched controls, no considerable structural or functional differences were observed in the heart of survivors of COVID-19. Lung ultrasound scan detected significantly greater residual pulmonary involvement in COVID-19 patients who had recovered from severe than mild-to-moderate illness. No significant differences were detected in ECG tracings nor were found in the left and right ventricular function of patients who had recovered from mild-to-moderate or severe illness. Conclusions: In a short-term follow-up, no abnormalities were identified in the heart of survivors of COVID-19, nor cardiac differences were detected between patients who had different severity of illness. With the limitations of a cross-sectional study, these findings suggest that patients who recover from COVID-19 do not have considerable cardiac sequelae. Graphic abstract: [Figure not available: see fulltext.

COG7 deficiency in Drosophila generates multifaceted developmental, behavioral and protein glycosylation phenotypes

Congenital disorders of glycosylation (CDG) comprise a family of human multisystemic diseases caused by recessive mutations in genes required for protein N-glycosylation. More than 100 distinct forms of CDGs have been identified and most of them cause severe neurological impairment. The Conserved Oligomeric Golgi (COG) complexmediates tethering of vesicles carrying glycosylation enzymes across the Golgi cisternae. Mutations affecting human COG1, COG2 and COG4-COG8 cause monogenic forms of inherited, autosomal recessive CDGs.We have generated a Drosophila COG7-CDG model that closely parallels the pathological characteristics of COG7-CDG patients, including pronounced neuromotor defects associated with altered N-glycome profiles. Consistent with these alterations, larval neuromuscular junctions of Cog7 mutants exhibit a significant reduction in bouton numbers. We demonstrate that the COG complex cooperates with Rab1 and Golgi phosphoprotein 3 to regulate Golgi trafficking and that overexpression of Rab1 can rescue the cytokinesis and locomotor defects associated with loss of Cog7. Our results suggest that the Drosophila COG7-CDG model can be used to test novel potential therapeutic strategies by modulating trafficking pathways

Factors influencing delayed discharge after day-surgery laparoscopic cholecystectomy: the DeDiLaCo study protocol

Objective: Laparoscopic cholecystectomy (LC) is the gold standard for most benign gallbladder diseases. Early discharge (<24 hours) has the same outcomes as longer (>24 hours) hospital stay. Nevertheless, the rate of delayed discharge >24 hours range from 4.6% to 37%. The primary endpoint of this Italian nationwide study is to analyze the prevalence of patients undergoing elective LC who experienced a delayed discharge >24 hours and identify potential limiting factors of early discharge. Results from these analyses will be used to select patients who can be safely discharged on the same day after surgery. Secondary endpoints will be to evaluate the patient's quality of life (QoL), assess the direct health costs associated with late discharge, and quantify the patient's involvement in the treatment process. Patients and methods: This prospective, observational study was conducted following a resident-led model and the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. All patients were treated according to the local hospital protocol and received routine care as standard therapy. Results: We expected to obtain the enrollment of at least 500 patients based on an assumed difference in discharge delay between the reference and the recruitable population of 6% and the identification of factors related to discharge failure within 24 h. Early discharge after LC leads to advantages both in terms of clinical outcomes and quality of life of the patient, and it is highly effective in terms of health costs and shortening the waiting list. However, clinical reality differs from the results of randomized studies by a complex series of non-objectionable real-world data influencing treatment plans. Therefore, we expected to identify independent predictors and factors of failure of early discharge. Conclusions: Clinical reality often differs from randomized trial results. In Italy, the vast majority of delayed discharges after LC may not be related to surgery and can be prevented both with logistical reorganization and with a readjustment of the trust reimbursement policies

Pre-Procedural Statin Use Is Associated with Improved Long-Term Survival and Reduced Major Cardiovascular Events in Patients Undergoing Carotid Artery Stenting: A Retrospective Study

Carotid artery stenting (CAS) is a minimal invasive procedure used to resolve carotid occlusion that can be affected by peri-procedural complications. Statin use before CAS has shown to reduce peri-procedural risk and improve survival, though time-dependent cofactors that influence mortality has not been considered. The aim of this study was to evaluate long-term survival of patients who undergo CAS considering new occurred major adverse cardiovascular event (MACE) as time-dependent cofactor. In this study, 171 high cardiovascular risk patients (age 72 \ub1 8 years, 125 males) were enrolled after CAS procedure and were followed for a median of 8.4 years. Death occurred in 44% of patients with a mean time to death of 69 \ub1 39 months and MACE in 34% with a mean time of 35 \ub1 42 months. In patients who used or not statins at baseline, death occurred in 33% and 65%, respectively (p < 0.001). Survival analysis showed that statin use reduced risk of death (hazard ratio HR 0.36, 95% confidence interval CI 0.23\u207b0.58, p < 0.0001). Including MACE as time-dependent variable did not change beneficial effects of statins. Additionally, statin use was associated with a protective effect on MACE (HR 0.48, 95% CI 0.27\u207b0.85, p = 0.012); particularly, the prevalence of stroke was reduced by 59% (p = 0.018). In multivariate analysis, effects of statins were independent of demographic and anthropometric variables, prevalence of cardiovascular risk factors, renal function, antiplatelet use, and MACE occurrence. In conclusion, use of statins before CAS procedure is associated with increased long-term survival and reduced MACE occurrence. This evidence supports the hypothesis that statin use before CAS might be beneficial in high risk patients