Processes leading to emergence of the asymmetric nodal domain differ depending on the mode of symmetry breaking. In Xenopus laevis and mouse embryos, the leftward fluid flow on the ventral surface of the left–right organizer leads through intermediate steps to enhanced activity of the nodal protein on the left side of the organizer and subsequent asymmetric nodal induction in the lateral plate mesoderm. In the chick embryo, asymmetric morphogenesis of axial organs leads to paraxial nodal asymmetry during the late gastrulation stage. Although it was shown that hedgehog signaling is required for initiation of the nodal expression, the mechanism of its asymmetry remains to be clarified. In this study, we established the activation of hedgehog signaling in early chick embryos to further study its role in the initiation of asymmetric nodal expression. Our data reveal that hedgehog signaling is sufficient to induce the nodal expression in competent domains of the chick embryo, while treatment of Xenopus embryos led to moderate nodal inhibition. We discuss the role of symmetry breaking and competence in the initiation of asymmetric gene expression.Development of visceral left–right asymmetry in bilateria is based on initial symmetry breaking followed by subsequent asymmetric molecular patterning. An important step is the left-sided expression of transcription factor  The key asymmetric “highway” is created by the left-sided expression of the TGF-beta ligand nodal and its downstream counterpart transcription factor pitx2 in the lateral plate mesoderm  morphogen in the floor plate is located directly above the prospective nodal domain in the left paraxial mesoderm, hence indicating a possible functional relationship. Sonic hedgehog is an early marker expressed in the organizer region and emerged in midline structures in various model organisms  at stage 9, indicating that shh is sufficient for nodal induction  or 2.5% (for chicken) Millipore water diluted in 0.1X MMR or PBS, respectively. Treatment of chick embryo was performed by application of 10 μl of the corresponding solution twice within 2 h to the ventral side of the embryos cultivated in a modified new culture as previously reported , indicating a nodal induction in the prospective somitic mesoderm. Right-sided nodal expression correlates with the right-sided expression of pitx2 in LPM. Furthermore, the SAG treatment interferes with cardiac development. While inhibition and local activation of hedgehog signaling lead to randomization of cardiac looping (shh, which is expressed in the endoderm (The activity of sonic hedgehog has been proposed to be upstream of the asymmetric dies cf.  that ind-domains . The aim looping , the gloendoderm , in the nodal induction during chick left–right patterning: despite the treatment of the whole embryos with SAG, the ectopic nodal expression was confined to the paraxial and the lateral plate mesoderm. As suggested previously, the left paraxial nodal domain is most likely induced by shh from the floor plate above (sensu lato also on specific transport and degradation of signaling molecules, enabling a local response to the global cue. The mechanism of predisposition of a certain mesodermal domain at the right side to respond to hedgehog activity with the nodal expression remains to be clarified: reported expression of the hedgehog pathway components gli or smoothened only partially overlaps with the prospective nodal expression domain. Further studies should clarify the basis of competence as well as the question of whether the lateral plate mesoderm in the chick is induced solely by a signal from the paraxial domain or possesses the ability to express nodal autonomously.Our results argue in favor of a crucial role of competence in the te above . This inte above . The thete above . It may nodal expression cannot be definitively resolved here, the complementary effects of hedgehog suppression that led to efficient nodal inhibition and of proposed hedgehog activation by SAG which induced nodal, strongly support the specific involvement of hedgehog activation in the reported effect. Furthermore, the toxicity of SAG treatment until the organogenesis stages was low.SAG has been used as a hedgehog activator in different models  and was Xenopus embryos. This functional divergence is in line with previously published data from other organisms. In the sea urchin, the inhibition of hedgehog signaling by cyclopamine was shown to suppress both asymmetric nodal and pitx2 expression (nodal expression (nodal antagonist DAND5 (nodal in the lateral plate mesoderm (nodal expression in mouse embryos lacking shh alone (shh and Ihh in the mouse. Moreover, mouse embryos lacking both smoothened and hedgehog repressor Gli3 display a correct left-sided pitx2 expression, indicating a functional redundancy (. Hence, detailed investigation of the exact mode of hedgehog activity in organisms with the leftward flow like Xenopus, mouse, or D. rerio can uncover unexpected levels of regulation.Activation of hedgehog signaling in our study led to different effects in chick and pression . In amphpression , while tst DAND5 . Interesmesoderm . Howeverhh alone , indicatdundancy . Hence, nodal expression at stage 5 in the competent paraxial domain. We suggest that this interaction is local and the asymmetry of nodal is achieved by the left-sided position of the posterior floor plate (To sum up, combined empirical evidence cf.  reveals or plate .shh-nodal interaction (nodal gene expression in the chick embryo.Furthermore, our data support the evolutionary divergence of eraction  and prov


Only a few studies have compared the outcomes of patients kept awake during endoscopic examination and subjects submitted to drug-induced sleep endoscopy.This study aimed to compare the endoscopic findings of patients submitted to outpatient endoscopy and endoscopic examination with sedation by propofol based on the Fujita Classification.This cross-sectional cohort study enrolled 34 patients. The subjects underwent ENT examination, nasal endoscopy with Müller's maneuver, and drug-induced sleep endoscopy with propofol. The Fujita Classification was used to compare the two modes of endoscopic examination. The examinations were correlated to patient clinical data such as BMI, age, and OSAS severity.There was no agreement between the two modes of endoscopic examination, whether for the group in general or for the analyzed subgroups.There was no agreement between the endoscopic findings of endoscopic examinations done with the patient awake or in drug-induced sleep. The studies performed on obstructive sleep apnea syndrome (OSAS) have enhanced the understanding of symptoms, facilitated diagnosis, and demonstrated the effectiveness of positive airway pressure therapiesThe vast array of approaches and the scarce controlled randomized trials hinder the demonstration of surgery effectiveness. Reviews and meta-analyses aimed at assessing OSAS surgery have presented inconsistent results: Sher et al.In these three important reviews, the authors inferred that the main cause for surgery failure is inaccurate identification of the site of obstruction in the upper airway and, consequently, poor patient selection. The complexity of the upper airways and the multifactorial character of sleep apnea explain the difficulties related to this assessment. The following tests are currently available to aid in patient evaluation: cephalometric measurements, computerized tomography, magnetic resonance imaging, airway mano-metry, fiberoptic laryngoscopy using Müller's maneuver, and drug-induced sleep endoscopy (DISE).,,,DISE with propofol has been increasingly used, and is currently considered as the endoscopic examination mode that more closely resembles natural sleep and allows for better location of the site of obstruction in the upper airways. Recent studies have ranked highly the effectiveness of this examination in terms of accurately locating sites of obstructionHowever, only a few studies have compared the outcomes of patients kept awake during endoscopic examination and subjects submitted to drug-induced sleep endoscopy. This study is essential in the assessment of whether endoscopic examination under sedation is required.This study aimed to compare the endoscopic findings of patients submitted to outpatient endoscopy and endoscopic examination with sedation by propofol based on the Fujita Classification.This is a multicentric study, with the following participating hospitals: University Hospital of the Medical School of Ribeirão Preto - University of São Paulo and the Samaritan Hospital between July of 2006 and January of 2010. All the enrolled patients were educated as to the nature of the study and signed an Informed Consent Form. The research protocol was assessed and approved by the hospital's Ethics Committee in Research with Humans (# 5620/2006).®) equipped with analytical software program Sleepscan Vision Analysis version 2.03.05. The following were recorded: electroencephalogram , bilateral electroocu-lograms , electrocardiogram (modified V2), surface EMG of the mental and submental muscle, bilateral EMG of the anterior tibial muscle, synchronized digital video (infrared camera - Elbex IncTM), and body position (Netlink body sensor positionTM). Breathing was monitored as follows: a pressure transducer cannula recorded the flow of air through the nose  in combination with a nasal and oral thermal air flow sensor ; respiratory inductance plethysmography belts were used to measure respiratory effort (Pro-Tech zRIP respiratory inductance plethysmographyTM); an oximeter (Netlink Head BoxTM) was used to assess blood oxygen saturation (O2 Sat) and a laryngeal microphone to record respiratory noises. All technical parameters were in accordance with the 2007 Manual of the AASM.The sample was made up of patients with a history of snoring and diurnal hypersomnia previously submitted to diagnostic nocturnal polysomnography at the hospital's Sleep Lab using a digital polygraph  and 12 females (27%) with a mean age of 41.35 ± 7.96 years and a mean BMI of 26.82 ± 3.62 were included. Based on polysomnographic testing, eight patients (17.4%) snored but did not have apnea, 19 (41.3%) had mild OSAS, 10 (21.7%) had moderate OSAS, and nine (19.6%) had severe OSAS.The exclusion criteria were: age under 18 and above 60 years and patients with cardiorespiratory comorbidities that increased the risk of sedation: previous AMI, congestive heart failure (CHF), severe chronic obstructive pulmonary disease (COPD), etc.The Fujita Classification was described in 1987 by Fujita and Simmons, and has since been widely utilized in the topographic description of upper airway obstruction. Type I includes isolated oropharyngeal obstruction ; type II features obstruction of the oropharynx and hypopharynx; and type III describes isolated hypopharynx obstruction.As a routine, during admission patients are submitted to physical and ENT examination, undergo awake fiberoptic laryngoscopy, and are assigned Mallampati and Friedman scores. Radiological examination data  were compiled from the patients' charts. Patients were kept in a seated position during fiberoptic laryngoscopy; the fiberscope was inserted in the nasal cavity after the application of topical vasoconstrictors. Two regions were assessed: na-sopharynx/oropharynx and hypopharynx, at rest and with the patient in Müller's maneuver. At this time, the patients were staged based on the Fujita ClassificationAnesthesia induction with propofol during DISE was carried out by an anesthesiologist. Cardiorespiratory parameters were monitored throughout the examination, and materials for intubation, airway access, and emergency medication were available in the operating room.® TCI, AstraZeneca) as described in the literaturePropofol was intravenously administered with the aid of a target controlled infusion pump  were carried out within 90 days.Weighted Kappa was used to compare the Fujita Classification subject scores on awake endoscopy and DISE and determine the level of agreement between the scores in both circumstances. The impact parameters such as BMI, age, and OSAS severity had upon the level of agreement between the examinations was assessed through ANOVA, Fisher's exact test, and weighted Kappa.Findings on velopharyngeal vibration and/or upper airway narrowing during DISE are described on The Fujita Classification, based on clinical assessment and DISE, is shown on Consensus states that the better and more accurate the characterization of the site of obstruction in patients with sleep-disordered breathing (SDB), the better the therapy and its results. The reviews cited in this paper have shown that outpatient endoscopy is not enough to properly stratify patients, as indicated by the inconsistent success rates reported for the analyzed surgical procedures,Drug-induced sleep endoscopy (DISE) has been considered by a number of recent studies as the examination that more closely resembles natural sleep, in addition to enabling dynamic, three-dimensional evaluation of the upper airways as the subject snores or suffers from episodes of apneaThere was no agreement in the Fujita Classification assigned to patients in awake and sleep-induced endoscopy (Kappa = −0.03). This disagreement may have occurred due to the lack of consideration given to specific conditions and characteristics of sleep, neuromuscular alterations, respiratory and postural patterns in deciding upon a therapy.Our findings are similar to those reported by Campanini et al.Another important finding as we analyze patients with agreeing or disagreeing Fujita Classifications and compare them for BMI, age, or OSAS severity, is that there is no clinical criteria to support the use of DISE. The lack of a correlation or pattern of obstruction reinforces the idea that each patient must be analyzed in an individualized fashion.The lack of agreement between the examinations proves that there is a marked neuromuscular component in the obstruction of the airways of subjects in their sleep, and that we are probably underestimating these findings when we base ourselves only on the endoscopic findings of awake patients.More studies are required to confirm the importance of DISE in the assessment of OSAS patients. However, this study has confirmed that the same endoscopic examination, when performed at different times, may yield conflicting results.The assessment derived from drug-induced sleep endoscopy differs from the evaluation produced from the endoscopic examination of awake subjects.


Older adults with frailty and sarcopenia are at high risk of disability. These older adults get benefit from physical activity. However, it is challenging to get them involved in exercise interventions. The SPRINtT trial has investigated the efficacy and feasibility of a multicomponent intervention in the prevention of mobility disability in older adults with frailty and sarcopenia in 11 European countries, under the coordination of the Università Cattolica del Sacro Cuore, Italy. Altogether 1566 candidates were recruited to the SPRINtT RCT, and 142 of them in Finland.The participants (n = 70) completed at least two years of physical activity training. The training was performed at moderate intensity and consisted of walking, strength, balance and flexibility exercises. The participants attended training two times a week at the center with the addition of home-based exercises. The training intensity increased gradually. The primary outcome of mobility disability was operationalized as an inability to complete the 400-m walk test. Secondary outcomes of physical performance were the short physical performance battery (SPPB) and handgrip strength.The results of the intervention will be revealed in spring 2020. Participants experienced that their physical performance improved during the follow-up. The physical activity program and the home-based exercises can be performed without any equipment and could, therefore, be easily implemented for practice.The physical activity intervention was feasible and could be further recommended for older people with sarcopenia and physical frailty if the final results support these experiences.


Under environmental governance constraints, in order to explore the quantitative contribution of green innovation efficiency to carbon peak and carbon neutralization at the urban level, this paper uses the unexpected Super-SBM model to measure the green innovation efficiency of each prefecture-level city based on the panel data of 40 prefecture-level cities in the Yangtze River Delta from 2010 to 2019. Furthermore, the panel fixed effect model is constructed, and the two-stage least squares estimation method is used for empirical research. It is found that green innovation efficiency can significantly reduce carbon emissions in the Yangtze River Delta, promote carbon emissions in the Yangtze River Delta to reach an early peak, and achieve the long-term goal of carbon neutrality as soon as possible. This conclusion is still stable after solving the endogenous problem and the influence of outliers. The results of regional heterogeneity analysis show that green innovation efficiency has remarkable effects on carbon emission reduction in Anhui and Zhejiang Provinces, and the emission reduction effect in Zhejiang Province is greater than that in Anhui Province. In addition, there exists obvious heterogeneity between different quantiles for the impact of green innovation efficiency on carbon emissions, showing an “inverted U” shape, and its intensity in the context of medium carbon emissions is greater than that of low carbon and high carbon emissions. While in 2013, China accounted for 28% of global carbon emissions, and per capita emissions exceeded those of the European Union for the first time [A large amount of evidence shows that global warming caused by anthropogenic greenhouse gas emissions (GHGs) has become one of the main challenges to human welfare ,2,3. Undrst time . By 2020In this regard, the Chinese government has put forward a series of emission reduction measures. At the Copenhagen climate conference, China pledged to peak its carbon dioxide emissions by 2030 and strive to achieve carbon neutrality before 2060. In order to achieve the strategic goal of carbon neutrality, China must change the mode of economic development and take the green low carbon development path of energy saving and emission reduction. That is, by changing the pattern of economic development and improving production efficiency, taking economic growth and energy conservation and emission reduction into account, we can realize green, low-carbon and high-quality development. In this case, as an important factor to achieve a win-win goal of environmental protection and technological progress, green innovation has become an inevitable choice for regions to win competitive advantages and achieve economic development under increasingly stringent environmental regulations . TherefoThe concept of ‘green innovation’ was first proposed by Fussler et al.  in 1996.At present, the research on carbon peak and carbon neutralization in the Yangtze River Delta is mostly based on the LMDI index decomposition method to explore the driving factors of carbon emissions and the scenario prediction method to analyze the peak time under different carbon emission scenarios. It is rare to discuss its quantitative contribution to the strategic goal of carbon peaking and carbon neutralization in the Yangtze River Delta from the perspective of green innovation efficiency. So, how does the efficiency of green innovation affect the strategic goal of carbon peak and carbon neutrality in the Yangtze River Delta? In this context, to answer this question, this paper uses the Unexpected Super SBM model to measure the green innovation efficiency of various prefecture-level cities in the Yangtze River Delta. On this basis, a fixed effect model is constructed to quantitatively analyze the quantitative contribution of green innovation efficiency to carbon peak and carbon neutralization. On this basis, this paper constructs a fixed effect model to quantitatively analyze the quantitative contribution of green innovation efficiency to carbon peak and carbon neutralization, and solves endogenous problems with instrumental variables. Additionally, this paper explores regional heterogeneity by grouping regression at the provincial level, and uses the panel quantile regression to explore the heterogeneity of the effect of green innovation efficiency on carbon emission reduction under different carbon emission intensities. Finally, this paper puts forward corresponding policy suggestions to promote the Yangtze River Delta region to achieve the long-term goal of carbon peak and carbon neutrality as soon as possible from the perspective of green innovation efficiency.The other parts of this paper are organized as follows: In a literature review of foreign studies, it is found that research on carbon emission reduction has a long history and has formed a large number of theoretical and practical results. These studies mainly focus on the influencing factors of carbon emissions, energy consumption and carbon emissions trajectory.The influencing factors of carbon emissions mainly include population size, economic development, per capita income and low-carbon technology ,14. Spec2 emissions of Korean industrial manufacturing in 1991 and 2009 from the perspective of multiplication and addition. They found that the intensity effect and structural effect have significant positive effects on carbon dioxide emission reduction in South Korea [2 emission reduction (ER30), a major shift in energy use patterns from oil and gas to electricity is required [Some scholars have conducted research at the enterprise or industrial level. Taking the enterprises in South American countries as the research object, Carmen Córdova et al. explores the impact of company size, assets and financial status at the enterprise level on whether to disclose carbon emissions and its evolution with the help of Logit and the linear panel data model . Jeong ath Korea . On thisth Korea . Vaillanth Korea . Ram M. required . Combing the relevant literature in China, scholars have studied the trajectory characteristics, driving factors, emission reduction strategies and peak path of carbon emissions from different spatial scales. Early scholars focused on the trajectory characteristics and important influencing factors of carbon emissions. Initially, scholars explored the decoupling between carbon emissions and economic growth using the Tapio decoupling elasticity coefficient ,27,28. WOn this basis, scholars predicted the time of carbon peak and carbon neutralization through scenario simulation and proposed differentiated peak paths. Such studies mainly focus on provincial and urban levels. Guo Fang and Wang Can used the Monte-Carlo method and K-means clustering algorithm to construct the index system to divide 286 cities in China into five categories: low-carbon potential cities, low-carbon demonstration cities, population loss cities, resource-dependent cities, and traditional industrial transition cities . In viewIn addition, some scholars considered the liquidity characteristics of carbon emissions to explore the linkage effect of regional collaborative emission reduction. Tan and Jiang used the Topsis method and gray correlation theory to comprehensively measure the coordination level of inter-provincial carbon emission reduction intensity in China from 2011 to 2019. They used the Gini coefficient, δ-convergence model, and the β-convergence model to analyze the unbalanced development trend of carbon emission reduction in China. They found that optimizing regional economic structure is conducive to promoting regional coordination of carbon emission reduction .To sum up, many scholars have conducted in-depth research on issues related to China’s realization of carbon peaking and carbon neutralization from a variety of perspectives, which provides a good reference for the early realization of the strategic objectives of carbon peak and carbon neutralization. However, the current research on carbon emissions in the Yangtze River Delta pays more attention to the current situation and peak path of carbon emissions, and the exploration of influencing factors is mostly based on the exponential decomposition method, rarely from the perspective of green innovation efficiency. Therefore, this paper selects the Yangtze River Delta urban agglomeration with developed economy, education, science, and technology to explore the quantitative impact of green innovation efficiency on carbon peak and carbon neutrality of the Yangtze River Delta urban agglomeration from the urban level. It is expected to provide relevant reference for the goal design of carbon peaking and the realization path of carbon neutralization in the Yangtze River Delta urban agglomeration. The possible marginal contributions of this paper are: This paper quantitatively analyzes the contribution of carbon peak and carbon neutralization of Yangtze River Delta urban agglomeration from the perspective of green innovation efficiency, enriches the research at the level of urban agglomeration, and provides relevant reference for the goal design of carbon peak and the realization path of carbon neutralization of Yangtze River Delta urban agglomeration.Firstly, compared with traditional innovation, green innovation has ‘double externalities’, which can achieve the ‘win-win’ of economic development and environmental benefits. Green innovation is considered an effective way to reduce pollution, reduce energy consumption, save energy and achieve sustained economic growth. Secondly, while maintaining high-quality economic development, it can take into account environmental benefits, achieve technological progress, promote the transformation and upgrading of industrial structure, and reduce carbon dioxide emissions by improving the efficiency of green innovation. Improving green innovation efficiency means technological progress, reducing carbon dioxide emissions from the source and achieving optimal innovation output at the lowest environmental cost. Improving environmental performance, enhancing competitiveness and upgrading industrial structure through green innovation has become a common practice around the world. Urban innovation activities promote the flow of R&D capital and funds to sectors with higher profits, and contribute to the concentration of green innovation resources, thereby promoting the improvement of industrial green technology, the improvement of output quality and the agglomeration of green innovation resources. The proportion of the tertiary industry with high value-added and low energy consumption will be increased. The market share of primary and secondary industries with large pollution, large energy consumption and less value creation may gradually decrease, thus optimizing the industrial structure. Therefore, the improvement of green innovation efficiency can effectively promote the reduction in carbon dioxide emissions in theory. Based on the above analysis, Hypothesis 1 of this paper is proposed:Hypothesis H1: Green innovation efficiency can reduce carbon dioxide emissions and promote the Yangtze River Delta region to achieve the long-term goal of carbon peak and carbon neutralization as soon as possible.There are great differences in economic development, technical level, environmental status and resource endowment among cities in the Yangtze River Delta; thus, there may be regional heterogeneity in the emission reduction effect of green innovation efficiency. In addition, carbon emissions and the peak progress of each prefecture-level city in the Yangtze River Delta are not the same, and innovation atmosphere and motivation are also significantly different. The green innovation efficiency of Yangtze River Delta urban agglomeration is unevenly distributed in space. Is the effect of green innovation efficiency on carbon emissions heterogeneous under different carbon emission distributions? Based on the above analysis, Hypotheses 2 and Hypotheses 3 of this paper are proposed:Hypothesis H2: The effect of green innovation efficiency on reducing carbon dioxide emissions has regional heterogeneity.Hypothesis H3: The effect of green innovation efficiency on reducing carbon dioxide emissions is heterogeneous at different carbon emission quantiles.This section may be divided by subheadings. It should provide a concise and precise description of the experimental results, their interpretation, as well as the experimental conclusions that can be drawn.To overcome the inherent limitations of traditional DEA model, Tone proposed SBM model by taking relaxation variables into account. To further distinguish the efficiency of effective decision-making units, Super-SBM model was proposed. The specific model is as follows: assuming that there are n DMUs, each DMU has m inputs and s outputs, and the Super-SBM model under the condition of variable returns to scale is:Two-stage least squares (2SLS) is a kind of instrumental variable method, which solves the endogeneity problems caused by missing variables, measurement errors and reverse causality by introducing instrumental variables. First, the endogenous variables and instrumental variables are regressed, and then the estimated values of the endogenous variables obtained from the regression are brought into the original regression equation to form a two-stage least square regression.The quantile regression can capture the extent to which the explained variables are affected at different quantile levels, making the estimation results more robust. To further explore whether the effect of green innovation efficiency on carbon emission is heterogeneous under different carbon emission distribution, this paper describes the whole conditional distribution of carbon emission by quantile regression, and estimates the impact of green innovation efficiency on carbon emission reduction under conditional distribution.2 emissions of 2735 counties in China. In the calibration of nighttime light data, the particle swarm optimization-reverse propagation (PSO-BP) algorithm is adopted to unify the DMSP/OLS and NPP/VIIRS satellite images to obtain high-quality stable nighttime light data within an extended period. The carbon dioxide emissions at the municipal level are derived from the CEADs database, which is aggregated by the carbon dioxide emissions at the county level.Carbon emissions calculation. Carbon dioxide emissions at prefecture-level cities come from the CEADs database. Chen et al. used the characteristics of high correlation between nighttime light data and human activities; two sets of nighttime light data (DMSP/OLS and NPP/VIIRS data) were provided by NGDC  to inverse the COThis paper uses the Undesirable-Super-SBM model to measure. In terms of the selection of input indicators, followed by the practice of Wu Chao et al. , Xiao LiThere are three main sources of data used in this empirical study. The carbon dioxide emissions at the municipal level are derived from the CEADs database, which is aggregated by the carbon dioxide emissions at the county level. The data and control variables involved in the measurement of green innovation efficiency mainly come from the China City Statistical Yearbook, Statistical Yearbook of prefecture-level cities, Statistical Bureau and Science and Technology Bureau of prefecture-level citiesAs shown in As shown in As shown in As shown in Considering that the data in this paper are balanced panel data, this paper designs a fixed effect model to empirically test the impact of green innovation efficiency improvement on carbon dioxide emissions in various prefecture-level cities in the Yangtze River Delta. The specific measurement model is designed as follows:The regression results of the model are shown in In this paper, the control variables that may affect regional carbon dioxide emissions and the fixed effects of regional and annual interference are added to the empirical model, which can overcome the endogenous problems caused by missing variables to a certain extent. This paper has confirmed that green innovation efficiency can significantly reduce carbon dioxide emissions in the estimation results of each model. However, new technologies and equipment invented by a region to reduce carbon dioxide emissions could boost green innovation efficiency in the region. To overcome the endogeneity problem that may be caused by mutual causality and improve the accuracy of estimation, this paper uses the green innovation efficiency of a province other than itself as the instrumental variable of green innovation efficiency, referring to the method of constructing instrumental variables by Su Danni . The ratOn one hand, the green innovation efficiency among different regions within a certain province is closely related, and the provincial government should plan the overall situation in the development process and not cut the innovation links among different regions. It ensures the correlation between instrumental variables and core explanatory variables. On the other hand, carbon dioxide emissions are carried out in the region, and the impact of green innovation efficiency in other regions on carbon dioxide emissions in the region is weak, which ensures the exogeneity between the instrumental variable and the explained variable. Therefore, the tool variable is reasonable.The results of two-stage least squares estimation (2SLS) using this instrumental variable are shown in the first and second columns of To eliminate the possible influence of extreme value samples on the conclusions of this study, the whole sample is reduced by 5%. That is, we remove the highest 5% sample and the lowest 5% sample of carbon dioxide emission, and then estimate Equation (1). The results are shown in the third column of There are great differences in economic development, technological level, environmental conditions, and resource endowments among prefecture-level cities in the Yangtze River Delta. Affected by regional location and administrative policies, there is a significant spatial imbalance in the efficiency of green innovation in various regions. Teng Tangwei et al. found that the green innovation efficiency of urban agglomeration in the Yangtze River Delta was on the rise as a whole, but there was heterogeneity among cities . TherefoThe regression results are shown in Based on the above empirical analysis, to further explore whether the effect of green innovation efficiency on carbon emissions is heterogeneous under different carbon emission distributions, this paper uses the panel quantile model proposed by Powell to describe the overall conditional distribution of carbon emissions through quantile regression and estimates the effect of green innovation efficiency on carbon emission reduction under the conditional distribution. Considering the endogeneity problem, the panel quantile model still adopts the mean value of the green innovation efficiency of a city’s province in addition to itself as a tool variable of green innovation efficiency. Additionally, this paper uses the Markov chain Monte Carlo algorithm to estimate parameters. The estimation results of the panel quantile model are shown in It can be seen from Based on the panel data of prefecture-level cities in the Yangtze River Delta from 2010 to 2019, this paper empirically explores the quantitative contribution of green innovation efficiency to carbon peaking and carbon neutralization in the Yangtze River Delta by using OLS regression, fixed effect model and two-stage least square estimation method. The conclusions are as follows: the green innovation efficiency can significantly reduce carbon emissions in the Yangtze River Delta, promote carbon emissions in the Yangtze River Delta to reach the peak as soon as possible, and realize the long-term goal of carbon neutralization as soon as possible. Additionally, this conclusion is still stable after solving the endogenous problem and the influence of outliers. In addition, the effects of green innovation efficiency on carbon emission reduction in Anhui and Zhejiang Provinces are remarkable, and the effect on Zhejiang Province is greater than that of Anhui Province at the provincial level. Moreover, the impact of green innovation efficiency on carbon emissions has obvious heterogeneity between different quantiles, showing an “inverted U” shape, and its intensity in the context of medium carbon emissions is greater than that of low and high carbon emissions.According to the research conclusion of this paper, improving the efficiency of green innovation is an important measure to reduce carbon dioxide emissions in the Yangtze River Delta region and realize the carbon neutralization of carbon peak at an early date.(1) In this regard, governments at all levels should improve policies and measures, focus on the adjustment and transformation of traditional industries and the development of new energy, energy conservation and environmental protection and other emerging industries, strengthen the research and development of green innovative technologies, establish and improve the internal incentive mechanism for green technological innovation, and stimulate the endogenous driving force of green innovation.(2) There is regional heterogeneity in the emission reduction effect of green innovation efficiency, so the regional gap of three provinces and one city in the Yangtze River Delta should be taken into account when formulating the strategic goal of carbon peaking and carbon neutralization. We should strengthen provincial planning, actively guide cities with high green innovation efficiency and cities with low green innovation efficiency to carry out various forms of innovation cooperation and exchange, and form a good inter regional collaborative innovation mechanism. Take effective measures to reduce emissions according to local conditions.(3) For regions with high carbon emissions, in addition to taking measures to improve the efficiency of green innovation, we should actively develop advanced green and low-carbon environmental protection technologies, adjust the industrial structure and energy structure, promote the transformation and upgrading of industrial structure, formulate practical emission reduction plans, improve management systems, strengthen institutional incentives, and promote the real implementation of the carbon peak goal in combination with our own resource endowment and development reality. For low-carbon emission areas, improving the efficiency of green innovation has little effect on carbon dioxide emission reduction. Therefore, we should speed up the transformation of economic development mode and cultivate new, environment-friendly and sustainable economic growth points.There are some deficiencies in this paper: (1) This paper measures the efficiency of green innovation with the help of the unexpected super SBM model. On this basis, this paper combines a fixed effect model, a two-stage least square estimation method and a panel quantile model to carry out research. Although the estimation results are well explained, this article does not take into account the possible spatial effects of variables. (2) The Yangtze River Delta region is increasingly showing a multi-center, networked spatial development phenomenon. However, this paper uses urban panel data and takes cities as independent samples, and has not considered the possible impact of the networked pattern of urban agglomeration in the Yangtze River Delta on variables.Therefore, in the next study, the possible spatial spillover effects of carbon emissions and green innovation efficiency will be fully considered, and the research will be carried out in combination with the current situation of the multi-center network of the Yangtze River Delta urban agglomeration. We expect to draw more meaningful conclusions in the next study, which will supplement and improve the research of this paper.


It should be considered as diagnosis of elimination, as some iatrogenic, infectious, or systemic diseases may cause similar oculo-renal manifestations. There is no clear therapeutic consensus. However, the rapid initiation of high-dose corticosteroid therapy was associated with favorable outcome in the majority of published cases, as well as in our patient.TINU  or oculo-renal syndrome was first described by Dobrin We report the case of an acute tubulointerstitial nephritis associated with uveitis in 11-year-old girl who presented with abdominal pain, vomiting and asthenia of one month. Laboratory tests revealed acute renal failure with proteinuria and aseptic leucocyturia. An inflammatory syndrome was found with erythrocyte sedimentation rate of 92 mm and inflammatory anaemia. Hypoproteinemia and polyclonal hypergamma-globulinaemia was found. No aetiology was found. The renal biopsy revealed a tubulo-nephritis with an interstitial inflammatory infiltrate of lymphoid cells and normal glomeruli. The patient was treated with high-dose of steroids . We noted a progressive improvement of the renal function and the appearance of ocular pain and a decrease in visual acuity. The ophthalmological examination revealed bilateral uveitis. The diagnosis of TINU syndrome was confirmed and the patient received steroids with progressive resolution of the uveitis.In the presence of any uveitis of unknown cause associated with disturbed renal function the diagnosis of TINU syndrome should be considered. This syndrome requires more precise diagnostic criteria and standardized management.None declared


The European Society of Cardiovascular Radiology (ESCR) is the European specialist society of cardiac and vascular imaging. This society’s highest priority is the continuous improvement, development, and standardization of education, training, and best medical practice, based on experience and evidence. The present intra-society consensus is based on the existing scientific evidence and on the individual experience of the members of the ESCR writing group on carotid diseases, the members of the ESCR guidelines committee, and the members of the executive committee of the ESCR. The recommendations published herein reflect the evidence-based society opinion of ESCR. The purpose of this second document is to discuss suggestions for standardized reporting based on the accompanying consensus document part I.• CT and MR imaging-based evaluation of carotid artery disease provides essential information for risk stratification and prediction of stroke.• The information in the report must cover vessel morphology, description of stenosis, and plaque imaging features.• A structured approach to reporting ensures that all essential information is delivered in a standardized and consistent way to the referring clinician.The online version contains supplementary material available at 10.1007/s00330-022-09025-6. In the last 20 years, new evidence has been added to the understanding of the physiopathology of the carotid-related stroke occurrence, by introducing the concept of the carotid artery vulnerability related to the plaque’s features. At the same time, a significant evolution in the imaging techniques has occurred by routinely allowing not only the degree of stenosis quantification but also the assessment of the plaque composition and the detection of the features of vulnerability.The European Society of Cardiovascular Radiology (ESCR) is the European specialist society of cardiac and vascular imaging. This society’s highest priority is the continuous improvement, development, and standardization of education, training, and best medical practice, based on experience and evidence. The present intra-society consensus is based on the existing scientific evidence and on the individual experience of the members of the ESCR writing group on carotid diseases, the members of the ESCR guidelines committee, and the members of the executive committee of the ESCR. The recommendations published herein reflect the evidence-based society opinion of ESCR. The purpose of this second document is to discuss suggestions for standardized reporting based on the accompanying consensus document part I.ESCR Consensus StatementIn reporting carotid artery atherosclerotic disease, assessment of stenosis severity should be complemented with information regarding plaque morphology and plaque composition. Some imaging biomarkers, described in the accompanying part I document, which are not yet validated by official guidelines should be reported and interpreted with caution.optional]. Some information is modality-specific . For broad application, this document does not include advanced approaches that are not considered standard or proprietary technologies.In this section, we will explain how and what information should be included in the report for the assessment of carotid artery pathology. We classified the information as [mandatory] and .Dual-energy CT with post-processing using 80–100 keV provides the most accurate estimates of calcification size, as compared to histology . It . It 4]. CTA is not yet considered a robust method to detect the presence of IPH but several studies suggest that some specific features are significantly associated with the presence of IPH in CTA: presence of the napkin sign , positivmandatory] , neutral, or inward (negative) [ry] Fig. . It is amandatory]. Alternatively, it can be expressed quantitatively with the eccentricity index (EI) of the plaque calculated as the ratio between the maximum thickness and minimum thickness at the point of maximum stenosis [optional]The eccentric or concentric morphology of the plaque must be at least visually evaluated . Th. Th15]. As previously stated, CT cannot assess the presence of lipid-rich necrotic core (LRNC) but can identify the presence of low-density areas that could represent LRNC. Basic assessment involves measuring attenuation density in a ROI in the plaque. More advanced assessment involves the calculation of the volume of plaque subcomponents.MR T2-weighted imaging can be used to detect the presence of LRNC . Direct When assessing the carotid plaque with high-resolution MRI, information on the fibrous cap status should be given by categorizing it as thick , thin, or fissured .optional].It is possible to include information with CT, regarding the perivascular fat density (PFD) measured as the attenuation value of the pericarotid fat. It should be measured as a circular/elliptic ROI obtained close to the point of maximum stenosis  as well as The presence and quantification of the severity of plaque (> 50%) in the common carotid artery (CCA) should be reported by describing the type .Vessel tortuosity can be classified according to the modified criteria of Weibel-Fields and Metz –25, whicDescription of any distal plaques should be reported in particular for the potential impact on surgical procedures. The presence of a severe distal carotid artery plaque should be defined as a “tandem” plaque . While tDescription of anatomy from the subclavian origin through to the basilar artery as well as the presence of at least moderate (> 50%) stenosis. Also, the superior cerebellar artery (SCA), the anterior inferior cerebellar artery (AICA), and the posterior inferior cerebellar artery (PICA) should be commented on in the report when the absence of these vessels is noted.Analysis of the circle of Willis should be included. The key information is (1) anatomy with the presence of variants  segments); (2) exclusion of aneurysms; and (3) identification of atherosclerotic (or other types e.g. inflammatory) lesions in the main arteries.While the vast majority of CT/MR examinations will be performed for diagnostic purposes, some patients will be referred for imaging after an intervention. Two groups can be distinguished: surgical intervention  versus deployment of a stent. In both instances, the main goal of imaging is the evaluation of the patency of the treated carotid artery segment, and the detection of possible complications. Possible complications include post-operative dissection, neo-intimal stent hyperplasia Fig. , restenoDuring the assessment of supra-aortic vessels, a differential diagnosis hypothesis can be formulated when typical features are detected. The definition of these multiple entities outside atherosclerotic disease is out of the scope of this paper and only some key elements are further described here.Carotid dissection is responsible for 20 % of ischemic strokes in young adults under 45 years and for about 2% of ischemic strokes overall . In MR, Fibromuscular dysplasia (FMD) is an idiopathic, non-inflammatory, and non-atherosclerotic disease with a prevalence between 0.3 and 3% in the cervico-encephalic arteries. The string-of-beads aspect is highly suggestive of FMD Fig.  31]. An. An31]. Carotid vasculitis can be defined as the inflammation of carotid artery walls with or without necrosis, leading to stenosis or occlusion of the lumen . VasculiWith CTA/MRA imaging, signs of carotid vasculitis are vessel wall thickening  and contrast enhancement. Usually, there is no preference for the involvement of the carotid bifurcation (different from atherosclerotic disease). In the case of active vasculitis, contrast enhancement of the thickened vessel wall may be seen on both CT and MR. Some authors suggest using T2-weighted TSE imaging for edema detection in mural inflammation but this is less sensitive and more vulnerable to artifacts compared to T1-weighted, fat-suppressed, contrast-enhanced, black blood MR imaging .Rarely, a solid tumor may be found along the course of the carotid arteries. A carotid body tumor is in typical cases located at the carotid bifurcation, splaying the internal and external carotid arteries but without invading the wall. This typical location together with the hypervascular nature is usually sufficient for a confident diagnosis.Radiation treatment can also induce non-atherosclerotic luminal narrowing as radiation-induced fibrosis . In a tymandatory]. All pathological findings should be reported at the end of the report as ancillary findings.The analysis should be completed with the assessment of the other visualized structures [The use of standardized and structured reporting for radiology examinations has gained significant momentum in recent years. However, it may come as a surprise that this concept is not new, as Preston Hickey proclaimed almost 100 years ago that “reports filed in hospitals should be scientifically accurate and should follow an accepted nomenclature, so at to have value in a statistical sense” .This formalized approach to delivering the information contained in imaging datasets following a pre-defined template has many advantages. As a standard model sharing the same language, it is a means to avoid errors of interpretation, as the reports will be mostly void of personal preferences in the way they deliver information . Also, iIt is well demonstrated that the simple missing information related to the modality of stenosis degree measurements  can deteA standardized and structured reporting could represent an advantage for the use of a correct and reproducible modality of information transfer among the different physicians by using a shared and unified model of presentation and interpretation of the information by reducing the overall frequency of errors .For these reasons, the ESCR has promoted structured reporting in its publications  and has ESM 1(DOCX 39 kb)


Dengue fever is a vector-borne disease affecting millions yearly, mostly in tropical and subtropical countries. Driven mainly by social and environmental factors, dengue incidence and geographical expansion have increased in recent decades. Therefore, understanding how climate variables drive dengue outbreaks is challenging and a problem of interest for decision-makers that could aid in improving surveillance and resource allocation. Here, we explore the effect of climate variables on relative dengue risk in 32 cantons of interest for public health authorities in Costa Rica. Relative dengue risk is forecast using a Generalized Additive Model for location, scale, and shape and a Random Forest approach. Models use a training period from 2000 to 2020 and predicted climatic variables obtained with a vector auto-regressive model. Results show reliable projections, and climate variables predictions allow for a prospective instead of a retrospective study. Aedes mosquitoes and affects approximately 100 million people every year. Although most infections are mild or asymptomatic, some may cause severe symptoms, leading to a higher risk of death. In the affected countries, the challenges associated with preventing and controlling dengue outbreaks have highlighted the need for novel tools. In this context, using statistical tools with climate and epidemiological information makes it possible to provide timely information to public health officials about the risk of dengue outbreaks, allowing the optimization of resources and preventive and non-reactive decision-making.Dengue fever is a vector-borne viral disease endemic to tropical and subtropical countries. The virus is transmitted by female  Aedes aegypti and Aedes albopictus .The mixed continuous-discrete probability density defines the ZAGA density function:The second method uses an RF approach. This method is based on the construction of bootstrapped ensemble of regression trees and combined such that the prediction variance can be reduced (see  and 25]25]). Onegamlss NRMSE):NWe used the dengue and climate data described above to fit the model in  using boOnce the transformed covariates in  are deteRRt as a covariate was used in the prediction of RRt+1. Once the predicted relative risks over the first three months of 2021 are computed, we compared the observed and predicted values with the NRMSE and NIS.95 metrics and show the behavior of the best six cantons and worst three cantons according to the latter metric, regardless of the method employed. The comparison is shown for the training period in NIS95 metric: see MSE and NIS metrics.Due to the auto-regressive nature of the model in , the preTogether with the expected values of the relative risks in The fitting performs well in the training period, except for some extreme observations that the model does not capture closely, for example, in Quepos and Montes de Oro. Moreover, the monthly trend over the testing period is well captured in Orotina and Desamparados and partially in Alajuela and San Jose, where for these last two cases, it is captured in two out of three testing points. In the case of Osa, the trend is captured, and the metrics are relatively low. Still, the excess uncertainty at the end of the testing period can be due to the observed behavior during the training period, where this canton suffered localized outbreaks, and the most recent data shows a marked decrease in the relative risk. The model has difficulties fitting both episodes. The uncertainty contains the trend information while it covers most of the observed values through the best-fit cantons.We also evaluated the capacity of the model to predict high-risk cantons vs. low-risk ones. Using the normalized Kendall distance, we computed the distance among rankings of observed relative risks and expected relative risks obtained by the best individual models of each canton. This exercise was computed with the three-time points of the testing period. In summary, the Kendall distances are respectively 28%, 39%, and 42% for those time points, showing that the ability to classify the model increases with the time horizon and assures that less than half of the cantons are classified accordingly to the observed rankings. However, we model and predict the relative risk for each canton separately, and we did not consider the spatial correlation among the cantons.Note that we obtained the above results by comparing two modeling alternatives based on the study of , which iIn this work, we implemented two statistical models, GAMLSS and RF, to predict relative dengue risk in 32 different cantons of interest for public health authorities in Costa Rica, incorporating predictions of climate variables. This approach overcame some limitations of the methodology implemented by Vasquez et al. , which iIn Costa Rica, the dynamics of dengue change geographically and temporally, so it has been necessary to carry out more localized studies to optimize health outcomes and address the specific local conditions that ultimately result in high-risk levels. By training the models with data from 2000 to 2020, our results showed that GAMLSS and the RF models successfully predict relative dengue risk in the testing period (first three months of 2021) in most of the cantons, capturing the trend and seasonality of the multiple time series. Although the model showed good performance in most of the cantons, the model’s predictive capacity had limitations in some cantons, including Montes de Oro, Quepos, and Upala. This cantonal-level analysis highlights the spatial heterogeneity of the effect of climate factors on dengue incidence, which reveals that the effect of those variables on dengue transmission on a local scale might differ from global expectations. The importance of climatic information regarding the incidence of dengue fever has been well established –8. HowevAs climate change progresses, extreme weather events such as heatwaves and unusually high rainfall are predicted to be more intense and frequent. A recent study  suggestsThe development of reliable early warning systems for dengue epidemics would allow for lowering the economic impact of the disease , 36 and Early warning systems (EWS) for vector-borne diseases are incredibly complex due to numerous factors originating from individuals, the environment, the vector, and the disease itself. However, creating reliable forecasting models may lead to fast decision-making processes that trigger disease intervention strategies to minimize the impact on a specific population . A finerS1 Fig(TIF)Click here for additional data file.S2 Fig(TIF)Click here for additional data file.S3 Fig(TIF)Click here for additional data file.S4 Fig(TIF)Click here for additional data file.S1 Table(XLSX)Click here for additional data file.


There has been growing interest on probiotics to enhance weight gain and disease resistance in young calves and to improve the milk yield in lactating animals by reducing the negative energy balance during the peak lactation period. While it has been well established that probiotics modulate the microbial community composition in the gastrointestinal tract, and a probiotic-mediated homeostasis in the rumen could improve feed conversation competence, volatile fatty acid production and nitrogen flow that enhances the milk composition as well as milk production, detailed changes on the molecular and metabolic level prompted by probiotic feed additives are still not understood. Moreover, as living biotherapeutic agents, probiotics have the potential to directly change the gene expression profile of animals by activating the signalling cascade in the host cells. Various direct and indirect components of probiotic approaches to improve the productivity of dairy animals are discussed in this review. Livestock production is a dynamic sector, critical to satisfying the growing demand for animal-sourced products and dairy products specifically have become a significant source of income for farmers contributing to the growth of developing economies . The incProbiotics are living non-pathogenic microbes and in many cases are also naturally present to some extent in the gastrointestinal tract. Over the years numerous bacteria and fungi have been identified as probiotics  Choct, . SupplemDairy production is considered to be among the top industrial sectors and global milk production reached nearly 906 million tonnes in 2020 . TherebyProbiotics are live beneficial bacteria that, when administered in adequate amounts, confer a health benefit on the host , often bLactobacillus johnsonii TP1.6 and Lactobacillus reuteri TP1.3B, to young calves increased the abundance of beneficial taxa including Bifidobacterium and Akkermansia in the intestine. Similarly, Bacillus amyloliquefaciens fsznc-06 and Bacillus pumilus fsznc-09 enhanced the relative richness of potentially beneficial bacteria in the rumen and intestine of weanling goats  in rumen fluid connected to the change in 18 genera of rumen fluid , Eimeria and Cryptosporidium, have been proven in several studies using various animal models  improved the host resistance to Eimeria-borne coccidiosis , Interleukin-6 (IL-6), and IL-1β in dairy cows  increased body weight gain of sheep and lambs. The growth-promoting effect was related to the increasing intestinal Lactobacillus and Bifidobacterium population and decreasing E. coli, Enterococcus, and yeast in the fecal contents.Primarily, probiotics could improve the rumen and intestinal epithelial cells growth that enhance nutrition uptake capacity. Probiotics implement these beneficial effects by improving the production of VFAs that act as growth promoters for epithelial cells . An inveBacillus amyloliquefaciens H57 could benefit the ruminant host by increasing nitrogen retention, feed intake, weight gain and reducing the methane emission in ruminants  increased the milk protein content. The reason was connected to the increased beneficial microbial population in the rumen, which enhanced the amount of microbial crude protein. Similar observations on ruminal microbial crude protein mediated increased milk and milk protein yield were reported by Saccharomyces cerevisiae, Bacillus subtilis and Enterococcus faecalis on milk production and milk composition in lactating goats by increasing milk fat, protein and total solid percentage in milk. Also, Saccharomyces cerevisiae on milk quality of dairy cows and reported that cows receiving probiotic supplementation produced more milk with higher fat content. Findings also included improved rumen pH, acetic and propionic ratio, indicating the influence of probiotics on increased milk fat content. Because after absorption, VFAs serve as precursors for milk synthesis . Growth factor-1 is a mediator of growth promoter hormone, whereas MCT-1 is associated with the rumen epithelium membrane transport system. The study does not present the evident correlation between milk productivity and probiotic mediated gene expression modulation. Yet, presumably, the increased expression of MCT-1 in lactating animals could induce higher uptake of VFA from rumen epithelium, resulting in improved milk production. Further identification of the active cellular components of probiotics that impact the gene expression profile related to milk production could open novel ways concerning the dairy industry.The second mode is probiotic-mediated modulation of the gene expression profile of lactating animal. A direct mechanism of probiotic mediated modulation of gene expression in the dairy animal has been observed by Probiotics implement a beneficial impact on dairy animals’ growth and milk production efficiency. The underlying mechanism is chiefly connected with the management of the rumen and intestinal microbial community. The probiotic mediated microbial homeostasis favors the positive nutritional balance and strengthens the general health of the lactating animal. These beneficial microorganisms propose a natural, consequence free approach to boost the dairy production.Besides general health advantages, probiotics could also serve as a potential biological source to improve the productivity of dairy animals. The natural mechanisms of probiotics include reducing disease burden, modulation of rumen metabolism and modulation of host gene expression. Collectively, it can be stated that the addition of probiotics in feed may enhance the yield of milk and improve the compositional quality of milk in lactating animals. However, the effects of the probiotics are influenced heavily by the strain variation, diet and host physiological state. Hence, developing new intervention strategies using probiotics or active molecular components from probiotics will be worth exploring.KN, NKM, and NR did literature search and prepared the draft. HD participated in preparation of manuscript. SK, MH, and AKP reviewed and edited the manuscript. All the authors contributed to the article and approved the submission.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Sustainable water resources management involves social, economic, environmental, water use, and resources factors. This study proposes a new framework of strategic planning with multi-criteria decision-making to develop sustainable water management alternatives for large scale water resources systems. A fuzzy multi-criteria decision-making model is developed to rank regional management alternatives for agricultural water management considering water-resources sustainability criteria. The decision-making model combines hierarchical analysis and the fuzzy Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS). The management alternatives were presented spatially in the form of zoning maps at the level of irrigation zones of the study area. The results show that the irrigation management zone No.3  was ranked first based on agricultural water demand and supply management in five among seven available scenarios, in which the scenarios represents a possible combination of weights assigned to the weighing criteria. Specifically, the results show that irrigation management zone No.3  achieved the best ranking values of 0.151, 0.169, 0.152, 0.174 and 0.164 with respect to scenarios 1, 4, 5, 6 and 7, respectively. However, irrigation management zone No.2  achieved the best values of 0.152 and 0.150 with respect to the second and third scenarios, respectively. The model results identify the best management alternatives for agricultural water management in large-scale irrigation and drainage networks. Accordingly, integrated water resources management focuses on water demand and supply management to achieve sustainable development. Water is a scarce resource essential for societal survival and functioning. This makes the application of integrated water resources management essential to cope with scarcity and the challenges posed by climate change and increased water demand to by expanding economies26. A conceptual framework combining integrated landscape management (ILM) and institutional design principles (IDP) perspectives was applied to analyze cooperation initiatives involving water suppliers and agricultural stakeholders from agricultural wastewater5. A national drought risk assessment for agricultural lands taking into account the complex interaction between different risk components was presented40. The research showed that crop diversification, crop pattern management, and conjunctive  water management can be effective in improving agricultural water48.Water management is becoming more challenging by the effects of climate change, population growth, and severe competition for water by the municipal, agricultural, industrial, and energy sectors34. The vulnerability was classified into two domains, i.e., sensitivity and adaptive capacity, and two spheres, natural/built environment and human environment. A geographical information system modeling and satellite data were developed for water management in agricultural areas by modulating the irrigation water demand based on several vegetation indices2. The water allocation rules were evaluated among water user groups considering environmental, economic, and social criteria involving agricultural water user groups across France51. Transferring of irrigation management was defined as the complete or partial transfer of responsibility for management and investment in irrigation systems from government institutions to water users and non-governmental organizations (NGOs)66. A combination of the Adaptation Pathways approach was used with the Soil and Water Assessment Tool (SWAT) to assess the actions under different climate conditions6.The management of today’s complex water supply and demand systems rely on assessment models combining climatic, social, economic, and environmental factors. A model was developed using the concept of risk by identifying hazards, exposure, and vulnerability65. Sustainability in basins with existing irrigation and drainage networks requires a strategic planning according to sustainable development principles38. Strategic planning refers to an organizational infrastructure that prioritizes plans and maximizes potential opportunities and benefits19. Sustainable development achieves present economic, environmental and social needs while fulfilling the needs of future generations. The lack of strategic vision with respect to sustainability practices and goals was discussed9. A SWOT analysis consists of well-structured strategic planning to assess the status of a system by evaluating its strengths (S), weaknesses (W), opportunities (O), and threats (T)58. A review of works based on SWOT analysis was reported25. A strategic approach was applied to water management in Africa with SWOT22. Strategic planning approaches were analyzed in Austrian flood-risk management by identifying background conditions to facilitate scaling and replication of catchment regional planning tools in flood-prone areas60. A raster-based regional conservation action planning tool was developed for prioritizing local and regional scale conservation actions in heterogeneous landscapes61.Conjunctive management requires a strong institutional capacity, which can be achieved through regional planning, based on a sound understanding of the interactions between surface water and groundwater47. A regional optimization model of crop water consumption using cellular automation (CA), crop suitability (CS), and a regional distributed crop water use model was applied to improve irrigation benefits in the context of regional water management28. A study was reported to determine deficiencies in irrigation networks and remediation measures1.A stochastic method was developed to determine the water availability in agricultural lands that resulted from drought management plans15. The AHP, is an approach that uses ratio comparisons among attributes and alternatives54. A method of scaling ratios using the principal eigenvector of a positive pairwise comparison matrix was proposed53. This work defines and measures the consistency of the pairwise comparison matrix by an expression involving the average of the non-principal eigenvalues.Multi-criteria decision making (MCDM) is a branch of operations research that provides methods for choosing among alternatives ranked by multiple criteria. The Analytic Hierarchy Process (AHP) is a widely used decision-making tool in various multi-criteria decision-making problems30. A review of the TOPSIS method for decision making was presented70. A new step‐wise weight assessment ratio analysis was introduced to determine the criteria weights in decision making problems33. The weights of the criteria were calculated using the integrated Stepwise Weight Assessment Ratio Analysis (SWARA)-SWARA-TODIM (an acronym in Portuguese for Interactive Multi-Criteria Decision Making) multi-criteria decision-making (MCDM) method52. The weighting methods in decision making process including the DEMATEL  and BWM (best worst method) was applied to achieve the importance of supplier criteria in a combined manner67. The fuzzy set in the form of a class of objects was introduced with a continuum of grades of membership69. The fuzzy extension of the AHP method was introduced64. Fuzzy TOPSIS method was applied for decision-making process17. The model integrating SWARA and Additive Ratio Assessment (ARAS) methods was introduced under uncertainty32. A new decision-making approach was developed by measuring attractiveness through a categorical-based evaluation technique and a new combinative distance-based evaluation method in a supplier selection problem during the COVID-19 pandemic44. The Level-based weight assessment (LBWA) in fuzzy environment was developed using actual score measures of the picture fuzzy numbers11. A novel extension of a developed multi criteria decision making (MCDM) algorithm known as the preference ranking on the basis of ideal-average distance method in fuzzy environment was applied to address a real-life complex decision making problem in social science research12. A comparative analysis of supply chain performances of leading healthcare organizations in India with three MCDM frameworks was reported10.The literature on methods and applications of Multiple Attribute Decision Making (MADM) has been reviewed and classified systematically45. The integrated Fermatean fuzzy information-based decision-making method was introduced based on the removal effects of criteria and the additive ratio assessment methods, and applied it to a food waste treatment technology selection problem49. A triangular intuitionistic fuzzy linear programming model was proposed for planning of sustainable production system in Baluchistan, Pakistan35. A fuzzy multi-criteria group decision-making model was investigated for watershed ecological risk management21. A fuzzy-TOPSIS-world open account (OWA)-based model was developed to identify the impacts of parameters influencing the water quality failure (WQF) potential31. A scenario-based fuzzy interval programming approach was developed for planning agricultural water, energy, food, and crop area management71. Game theory was applied for solving decision making problems. The method was applied to construction site selection, and demonstrated that game theory can be applied for supporting decision in a competitive environment46. SWOT analysis can be improved by combining it with MCDM37. The Analytic Hierarchy Process (AHP) and the Analytical Network Process (ANP) analysis have been combined with SWOT analysis68. Multiple criteria group decision making applied for prioritizing SWOT factors23.Uncertainty analysis was conducted using an integrated fuzzy lambda–tau and fuzzy multi criteria decision-making method63 and research on sustainability principles4, sustainable agricultural water management at the local level and scale has received less attention. Studies by the Organization for Economic Co-operation and Development (OECD) on water sustainability indicators show that analysis at the local level and scale is necessary to demonstrate the effectiveness of the principles of water sustainability41.Despite numerous studies on sustainable water management by researchersThe analysis of large-scale water resource systems involving multiple components, resources, stakeholders, reservoirs, small irrigation reservoirs, and water transfer schemes is a complex process. This work develops and applies a conceptual framework for sustainable agricultural water use and supply by applying regional management alternatives at multiple spatial scales. The framework is applied to a large scale water resources system considering social, economic and environmental factors. The framework applies conceptual and analytical methods to sustainable agricultural water management relying on strategic planning and regional multi-criteria decision-making. Previous works have evaluated the sustainability of water resources from different perspectives and methods. This study is novel in its introduction of a framework that measures the sustainability of large-scale agricultural water systems relying on regional management plans.8. Effective implementation of integrated water policies is not common, and has led to a policy implementation gap that leads to incapacity in translating policy into action7. This work contributes to closing that gap.This section presents the conceptual framework for agricultural water demand and supply management and explains how to apply the conceptual framework for developing regional management alternatives see Fig. . It is sThe main purpose of strategic planning is to identify and analyze internal factors (strengths and weaknesses), external factors (opportunities and threats), and to formulate management alternatives for sustainable development of agricultural water management. The strategic planning stage considers agricultural water use and sources, social, environmental, and economic issues. The evaluation of the internal and external factors and determining the strengths, weaknesses, opportunities, and threats, and the current status of water resources leads to the formulation of sustainable agricultural water management plans, which is the basis for determining the regional priorities in the form of regional management alternatives.39. The selected management alternatives defined in the first stage are formulated as a set of regional management alternatives for sustainable development of agricultural water management. Notice therefore that the output of the first stage is a set of management alternatives for sustainable development of agricultural water management, which constitutes the basis for defining regional management alternatives in the second stage. The management alternatives can be structural, non-structural, or a combination of both, which are addressed in terms of water demand and supply management.Spatial multi-criteria decision making analysis integrates spatial and non-spatial data and incorporates them in the decision-making process. This is accomplished by defining the relationship between input and output maps where by the spatial data and the priorities of the decision makers are accounted for and analyzed according to the rules of decision makingThis work implements multi-criteria decision making models to prioritize the irrigation management zones in terms of regional management alternatives for agricultural water demand and supply management. The proposed model implemented to prioritize the irrigation management zones is a combination of hierarchical analysis and the TOPSIS in a fuzzy environment.Sefidroud irrigation and drainage network, Iran, with an area of 284,000 hectares  and external factors (opportunities and threats) related to agricultural water management in the study area.Determining the regional management alternatives of agricultural water demand and supply management.Multi-criteria analysis of the regional management alternatives of agricultural water demand and supply management.This section describes the following topics:Sefidroud network, local rivers, drainage, small irrigation reservoirs and groundwater resources), the crop pattern and quality of soil and water sources vary throughout the study area. Therefore, a database of water-use statistics was prepared to estimate the water use by agricultural lands within the Sefidroud irrigation and drainage network. The water use in the agricultural lands is a function of various factors such as the type of water resources, the method of water conveyance and distribution, the irrigation method, the type of crop products, climatic conditions, soil type, management practice, and others. Therefore, estimating the amount of water use in the agricultural areas in the study area is beset by complexity  the cultivated area and crop pattern of irrigated lands, (b) the crop water requirements, (c) the irrigation efficiencies and (d) the surface and ground water withdrawal data. The agricultural water use analytical model calculates water use in each irrigation unit by comparing the water requirements of the crop pattern with the water withdrawals of surface water and groundwater. The outputs from this model are actual water use, the contributions of surface and groundwater to water use and the volumes of return flow.Sefidroud dam and its related channels, local rivers, farm wastewater, small irrigation reservoirs, and groundwater) within the irrigated units of the Sefidroud irrigation network are depicted in Fig. Sefidroud irrigation and drainage network has been estimated at about 179,181 hectares. The total annual water use of cultivated area in Sefidroud irrigation and drainage network is about 1.8 billion cubic meters, of which about 1707 million cubic meters (95%) are surface water and 90 million cubic meters (5%) are groundwater. Of the total volume of surface water use about 1.4 billion cubic meters are from the Sefidroud dam and related canals, 260 million cubic meters from local rivers and farm wastewater, and about 47 million cubic meters from small irrigation reservoirs. The average volume of water use in the 191,141 hectares of irrigated lands of the Sefidroud irrigation and drainage network equals 9404 cubic meters per hectare.The details of agricultural water use from different water sources . This study separates internal and external factors by the geographical boundary of the irrigation network. Thus, the factors under the management of Sefidroud irrigation network; (2) Improve the management of operation and maintenance of the Sefidroud irrigation network; (3) Wastewater management, and (4) Inter-basin water transfer within the Sefidroud irrigation network system  Development/Rehabilitation of the network;  WastewatSefidroud irrigation and drainage network were defined according to the management alternatives for agricultural water demand and supply management, and are shown in Figs. The spatial distribution of the management alternatives within the Sefidroud irrigation network’s infrastructure has not been fully implemented. Accordingly, completion and implementation of the main irrigation and drainage network in about 90,000 hectares represents one of the most important priorities in the Sefidroud irrigation network. Carrying out this management alternative would raise the irrigation efficiencies of the Sefidroud irrigation network. Furthermore, in spite of the implementation of the main irrigation and drainage network in 10 irrigation units of the Sefidroud irrigation network, the rehabilitation of the irrigation network in 102,000 hectares is imperative to achieve operational effectiveness. Figure Sefidroud irrigation network.Under current conditions the management alternative of development/rehabilitation of the Sefidroud irrigation and drainage network. The spatial distribution of small irrigation reservoirs is depicted in Fig. One of the effective management alternatives for maximum use of internal water resources in the study area is using the natural potential of small irrigation reservoirs existing in the Sefidroud irrigation and drainage network, which includes the Markazi, Fumanat, and Shargh irrigation zones, is accomplished with hierarchical analysis methods56 and the TOPSIS decision-making method in a fuzzy environment, which consists of the following stages14:Determining appropriate criteria for the decision-making process.Calculations related to the hierarchical analysis process.Evaluating the alternatives using the fuzzy TOPSIS model, and determining the final prioritization of alternatives.A fuzzy multi-criteria decision model was implemented to evaluate the agricultural water demand and supply management alternatives. The prioritization of the regional management alternatives in the The alternatives and criteria for decision making are determined and a hierarchical structure is formed. The hierarchical structure has a first level consisting of goals to be achieved, the second level consists of the decision criteria, and the third level consists of the management alternatives.55, and the weights of the criteria are calculated based on the geometric mean values. The next step applies the fuzzy TOPSIS algorithm to evaluate the management alternatives in each of the irrigation management zones of the Sefidroud irrigation and drainage network. Lastly, the management alternatives are prioritized. The prioritization uses language variables to evaluate the management alternatives. The fuzzy TOPSIS calculates the CCj indexes of the management alternatives, such that the alternatives’ rank or desirability increases with increasing value of the CCj index. The CCj index is a dimensionless metric in the range  that measures the closeness of a management alternative to an ideal management alternative or solution29.The weights of the criteria are determined by the hierarchical analysis method once the hierarchical structure is defined, which involves constructing a pairwise comparison matrix to determine the weights. The comparison matrix’s values are determined using Saaty’s tableSefidroud irrigation and drainage network to enable accurate decisions representing zonal conditions. Recall that three irrigation management zones of Sefidroud irrigation network are considered. The identified criteria are listed in Table The decision criteria are of central importance for evaluating the agricultural water demand and supply management alternatives. All the factors that are considered influential in the sustainable management of agricultural water must be studied. The decision criteria are studied separately for each of the irrigation management zones of the i and j, are normalized in the interval .The criteria listed in Table -) are defined as The fuzzy positive ideal solution  and the fuzzy negative ideal solution  and negative (D−) ideals, and the CCj indices are computed with TOPSIS14. The calculation results for the CCj index are listed in Table Fumanat irrigation zone) with CCj index equivalent to 0.151 is selected as a first priority (top rank) as an agricultural water-demand and supply-management regional management alternative. The lowest priority (bottom rank) of alternatives based on the CCj index is listed in Table j values is also shown in Fig. All the criteria used in this work to rank of the agricultural water management alternatives are benefit criteria. The distance between the alternatives and the positive  has the largest CCj value equal to 0.174 compared to its initial value of 0.151. The scenario, in which the weight of the third and fourth criteria are changed, establishes that alternative A1 (Markazi irrigation zone) has the larger CCj value equal to 0.163 compared to its initial value of 0.145. Also, the second scenario, in which the weight of the first and second criteria are changed, indicates that alternative A2 (Shargh irrigation zone) has the largest CCj value equal to 0.152 compared to the initial value of 0.50.The end product of the multi-criteria analysis process consists of proposing an alternative or a set of alternatives for implementation. Sensitive numerical inputs that may have a major impact on the final decision  must be identified. The purpose of sensitivity analysis is to determine how the proposed alternatives are affected by changes in inputs . This analysis evaluates the robustness, or lack of it, of the proposed solution. The sensitivity analysis is performed by changing the weights of the decision making criteria. There are seven combinations of the weights, each defining a weighting scenario, which are listed in Table This work develops and applies a conceptual framework of strategic planning and multi-criteria decision making for sustainable agricultural water management. Also an analytical model for estimating agricultural water use based on multiple factors was developed. The results of the agricultural water use analysis and the identification of internal and external factors affecting the management of agricultural water resources led to defining regional management alternatives for agricultural water demand and supply.Sefidroud irrigation and drainage network) was developed based on four water resources sustainability criteria: social, economic, environmental, and water use resource management. The presented framework combines the method of analytical hierarchy and the fuzzy TOPSIS, which permits taking into account the effect of the criteria weights in multi-criteria decision making. The study’s results showed that alternative A3 (the Fumanat irrigation zone) was top ranked (first priority) among other irrigation zones as the best regional management alternative. The sensitivity analysis results have demonstrated that in five among seven scenarios the Fumanat irrigation zone was ranked first with respect to regional management alternatives for agricultural water demand and supply. The framework developed in this work can be applied to other large scale water resources system in which regional differentiation is essential for sustainable water management.Decision making involves the use of a method that accounts for uncertainty within the decision-making process. Hence, a model of decision making with regard to the alternatives (the irrigation management zones of the


Thoracic aortic rupture may present with subtle clinical and CT-angiography findings. Recognition of the imaging features of early rupture is key for timely diagnosis and treatment. This report presents a new sign of incipient proximal thoracic aortic rupture on CT-angiography. Aortic emergencies are a diagnostic and therapeutic challenge due to their life threatening potential if not promptly diagnosed and treated . Acute aPAU represents 2-7% of acute aortic syndrome cases and is defined as an atherosclerotic lesion with an ulceration which penetrates the aortic innermost layer (tunica intima) and the internal elastic lamina; when the ulceration reaches the middle layer (tunica media) of the aortic wall, it determines blood accumulation and leads to IMH formation . PAU incA common differential diagnosis for PAU is the ulcer-like projection (ULP), which represents a newly formed local disruption of the intima layer, with a wide connection to the aortic lumen, seen in IMH undergoing unstable evolution: the blood fills the IMH and enlarges it, increasing the risk of aortic dissection and rupture ; moreoveWe present a case of acute aortic syndromes due to a PAU of the descending thoracic aorta, with associated acute IMH and superimposed ULP originating from the periphery of the PAU intimal entrance port.A 77-year-old woman with a past medical history of uncontrolled hypertension, presented to the emergency room with 24 hours of unrelenting sudden-onset chest and back pain . ElectroUnenhanced CT phase showed a thin, but extensive IMH propagating along the proximal thoracic aorta . A hyperCTA showed a focal contrast-filled outpouching of the proximal descending thoracic aorta, representing the PAU, associated with a ULP originating from the entrance port of the PAU, inside the IMH . On arteSymptomatic PAU and the associated ULP were treated with TEVAR, placing a RelayPro Thoracic Stent-Graft System  starting from under the aortic isthmus to the distal thoracic aorta. The descending aorta was not covered completely, to avoid the risk connected to Adamkiewicz artery occlusion.The unrelenting chest and back pain vanished instantly after the TEVAR. After 1 month, CTA evaluation reported a complete reabsorption of the IMH and a complete exclusion of the PAU and ULP . FurtherAcute aortic syndromes are associated with high mortality and morbidity; it is mandatory to find and distinguish radiological features of acute aortic syndromes and rupture to guide the diagnosis and treatment. Imaging findings of thoracic aortic rupture seen at unenhanced CT include hemomediastinum (striped opacities or hyperdensity in the mediastinum), hemothorax, or hemopericardium; the hemorrhagic component measures more than 30 Hounsfield units (HU) in density and can be better detected at unenhanced CT scans. Contrast-enhanced CT scans help to identify the type of acute aortic syndrome and could show contrast medium extravasation .In the reported case, the PAU is associated with a relatively extended IMH in a long segment of the descending aorta, and the IMH has been worsened by the subsequent formation of a ULP. All these pathological and symptomatic aortic entities were simultaneously present in our patient and required prompt treatment. To the best of our knowledge, ours is the first case of a symptomatic PAU-IMH associated with a ULP attached to the intimal opening of the PAU.Furthermore, the presented case showed a mediastinal blood spread, exploiting the periesophageal and extrapericardial cardiac recesses , reaching the sloping portion of the interface between the visceral (posterior) mediastinum and the prevascular mediastinum (front). This CTA appearance, which we have called the “bib” sign, represents a sign that can be observed in the first moments of rupture (contained rupture) of the descending thoracic aorta. When this sign is observed at unenhanced CT examination, a possible cause of anterior wall rupture of the proximal descending thoracic aorta must be searched. In other words, the presence of the getaway offered by the extrapericardial recess below the left branch of the pulmonary artery allowed the initial blood spread not to form a periaortic hematoma in the virtual space anterior to the proximal descending thoracic aorta but to flow out anteriorly.