Previous studies on voting bias in competitive awards have not fully considered the role of cultural similarity. Using data for the Best FIFA Men’s Player Award, we evaluate the extent of voting bias in this Award using three cultural similarity factors , six established in-group factors  and the impartiality of the voter’s country. Using statistical and econometric methods, we find that voter-player cultural similarity is positively associated with voting bias and find no evidence of impartiality when it comes to cultural or national ties. We also find that media voters are less biased than captain voters and coach voters, and that coaches are less biased than captains. Awards play an important role in many industries, especially sports and entertainment. Some of these awards use voting to determine which candidate should win the award. For example, the National Basketball Association (NBA) has a panel of sportswriters and broadcasters who vote for the Most Valuable Player Award, the Eurovision Song Contest has competing countries cast votes for the other countries’ songs, and members of the Academy of Motion Picture Arts and Sciences nominate and vote for Oscar winners. Given the importance of such awards, researchers have examined how voters can be unfairly in favor or against a candidate , 2.From this prior research, there is ample evidence that voters are guided not only by the quality of the candidates but also by established in-group biases –5. This We investigate voting bias in the Best Fédération Internationale de Football Association (FIFA) Men’s Player award  using established in-group and cultural factors. We use seven years (2010–2016) of data for the Award. Officially, the Award is determined by “the best in their category, without distinction of championship or nationality for their achievements during the year” . Thus voIn addition to concerns about favoritism, the Award is useful for studying voting bias for three reasons. First, we can examine how multiple in-group factors, including geographical, nationality, ethnicity, language, religion, voter type, club, league, and variables for player performance, interact to influence voter bias over time. Second, the Award is global and offers extensive information about the voters, the candidates, and how votes were cast. Each year there are three types of voters  from approximately 200 countries. Each voter has three votes to assign to a shortlist of 23 player candidates (referred to as ‘players’), awarding 5 points, 3 points, and 1 point to their selected players. The single player that receives the highest cumulative total number of points wins the Award. This international context, and the accompanying substantial cultural differences, are useful for examining the role of cultural similarity between voter and player on voting bias. We do this by unpacking cultural similarity into three factors: cultural distance, cultural clusters, and voter collectivism. We use a well-established methodology for measuring voting bias that calculates the difference between the number of points awarded to a player by a given voter and the average number of points awarded by all other voters to said player. Lastly, the Award provides a practical context for investigating how a voter’s country’s impartiality might affect voting bias.Our results show that voting bias exists in the Award. We find that cultural distance, cultural clusters, collectivism, and geographical distance all impact voting bias. We also find that when voters and players share nationality, club, league, or are country neighbors, then voting bias is positively correlated. In terms of the bias exhibited by different voters, media voters have a significantly lower voting bias than captain voters and coach voters, and coaches have a lower voting bias than captains. Overall, our findings show that something other than player quality  can be attributed to the voting results. This analysis provides new insights into how cultural similarity and impartiality influence bias in peer voting and international award competitions.In the context of sports, prior research has examined voting bias in the seeding of basketball teams , 16 and A few studies have examined voting bias in the Award (under its current or former names) which is the focus of our study. Focusing on the role of cultural diversity, Ruizendaal  found noVoting bias can be explained using social identity theories , 29 and Prior research on awards has found that the basis for voter-player similarity includes factors such as gender , 34, racHypothesis 1:Voters are more likely to choose players with similar in-group factors .Given that cultural similarity is a recognized determinant in social identity theory for explaining intergroup behavior such as bias, we now develop a hypothesis for how three characteristics of cultural similarity  impact voting bias in the Award. Our fundamental premise is that cultural distance, and cultural clusters are an important element of voters’ calculations (conscious or unconscious) of their similarity to the players, which influences the likelihood of voting bias. Furthermore, voters from countries with strong collectivist cultures will emphasize the group rather than the individual and will more likely favor those within or close to their cultural group.Hofstede’s , 38 reseOur second factor used to characterize cultural similarity between voters and players is cultural clusters. GLOBE researchers  used datOur third factor for characterizing cultural similarity is collectivism. Hofstede 43, p. 348) defines collectivism as “a preference for a tightly-knit social framework in which individuals can expect their relatives, clan, or other in-group to look after them, in exchange for unquestioning loyalty.” In contrast, individualism is “a preference for a loosely knit framework in society in which individuals are supposed to take care of themselves and their immediate families only” . Consequently, collectivist cultures are more likely to exhibit loyalty and support to those in their in-group , 42, 43., p. 348 The GLOBE data set divides collectivism into two dimensions: collectivism I  and collectivism II (in-group collectivism). The first form of collectivism is the extent to which society encourages individuals to be integrated into groups; the second is the degree to which individuals express loyalties to their families or in-groups , 45. We Hypothesis 22A: An increase in cultural distance between a voter and a player will decrease voting bias.2B: Voters and players that reside within the same cultural cluster will have higher voting bias relative to those that do not live within the same cultural clusters.2C: Voters from collectivist cultures will have a greater voting bias than those from individualistic cultures.Our final hypothesis explores how the impartiality of a voter’s country impacts voting bias within the cultural clusters defined in hypothesis 2B. An impartial government  will treat individuals within its country in an impartial manner regardless of race, ethnicity, family/political ties, or social standing . ImpartiHypothesis 3:The impartiality of a voter’s country reduces cultural voting bias.We use data provided by FIFA to investigate voting bias in the 2010 through 2016 Award years. The dataset consists of 10,305 votes from 3,435 voters spanning seven years. As shown in We also incorporate the GLOBE data set  on cultubjk represents the voting bias between voter j  and player k; pjk is the number of points awarded by voter j to player k ; and, all other voters to a player k . The average number of points awarded by all other voters is defined as:njk is the total number of voters awarding points to player k (less the one vote from voter j). Note that for every vote and the corresponding points awarded, we calculate the average points awarded from all other voters, excluding the points given from voter j to player k. This specification of the dependent variable has the advantage of being a continuous variable that includes a proxy of player quality  that could be determinants of voting bias. Data for nationality, league, and the football club for players and captains was collected using  country . We use  country , we test country .i) according to their respective nationality. Next, we determine the squared Euclidean distance between each voter (j) and each selected player (k) based on Hofstede’s values (i) of the six dimensions and divide by the number of distance relationships (n x (n– 1)) multiplied by the number of cultural dimensions . Finally, we take the square root of the term as shown in For our second hypothesis, we use the three factors related to cultural similarity: cultural distance, collectivism, and cultural clusters. For cultural distance, we use Hofstede’s six cultural dimensions and the nine cultural dimensions of GLOBE. Hofstede’s dimensions  are on a scale of 0 to 100. In contrast, the GLOBE dimensions  are on a scale of 1 to 7. We use both sets of cultural dimensions in different ways to investigate cultural variation and its impact on voting bias. The first technique involves calculating Euclidean distance to represent the cultural distance between voters and players. This calculation requires several steps. First, each player and voter are assigned a value for each of the six Hofstede dimensions , Ij represents the respective index of the voter, and Ik represents the respective index of the player. Lastly, Where Voter collectivism is a measure ranging from a value of 0  to a value of 100 for maximum collectivism. As discussed, we hypothesize that a voter from a more collective society  would have greater voting bias than a voter with lower collectivism. Likewise, we investigate the relationship between two cultural dimensions of the GLOBE study associated with collectivism  and voting bias.CCjk) is used to identify voters and players from countries that are defined within the same cultural cluster or not. This indicator reflects voting bias between voters and players who share the same cultural cluster.Our final measure of cultural similarity utilizes cultural clusters defined in research through the GLOBE study , 45. As For our third hypothesis, we measure impartiality using ‘quality of government’ data from the International Country Risk Guide (ICRG) . This meCCjk) is expected to be positive and significant, implying that positive voting bias exists between voters and players who share the same cultural cluster. According to our hypothesis and based on similar research conducted by Charron [CCjk x impartiality Imj) should be negative and significant, implying that voting bias across countries defined by their cultural clusters diminishes significantly as impartiality (Imj) increases. This finding is consistent with similar results of Charron [We use an interaction term of impartiality with cultural clusters to test our final hypothesis (similar to Charron ). If cul Charron , the int Charron  that demposskt, defencekt, and attackkt come from Squawka (http://www.squawka.com) and are used as additional performance metrics as only three years of performance data is available. The Squawka Player Performance Score uses data from the Premier League’s official data provider Opta and uses an algorithm to rate players based on real-time play components; attack, defence and possession. The attack score takes all the attacking events into consideration , the defence scores defensive actions  and the possession score analyzes passes, through-balls, etc. The algorithm scores each event independently.We collected six performance variables for this study, three of which were found to be valuable in this study. The three variables used are: the percentage of games won, the goals per game, and the assists per game. These data were collected from websites specializing in providing football statistics: footballdatabase.eu and squawka.com. Each variable is a performance metric based on a player’s performance in all games . k received in year t; “wpcentkt”, “gpgkt” and “apgkt” are performance variables ; and “ak” is the “player fixed effect” which is a constant representing the unobserved effect on the percentage of votes received by player k due to “being” player k. In this way, we interpret the unobserved effect as the potential for voting bias associated with individual players.We test our three hypotheses using econometric methods. The first method employs a fixed-effects regression model to predict the percentage of points earned for each shortlisted player over the 7-year time frame using only the performance characteristics collected for this study. In this way, we control for the individual heterogeneity of the players and test if individual heterogeneity (or unobserved factors not related to performance) is a significant factor in the competition. This method provides a statistical model to test our first hypothesis of whether voting bias exists. Two general assumptions justify using the fixed-effect model to investigate the presence of voting bias. The first assumption is that the performance variables  can sufficiently capture a player’s performance. Second, the percentage of votes that a nominee receives each year is determined largely by the performance of that nominee in that calendar year. Therefore, any unobserved effects  influence voting results that are not related to performance. In other words, if individual heterogeneity is statistically significant, something other than performance contributes to the percentage of points received, thus allowing us to infer the possibility of voting bias. The player fixed-effect model can be represented by:j and player k in year t and Xjkt represents various explanatory and control variables. The benefit of this specification is that the dependent variable is continuous , allowing us to investigate our hypotheses and easier interpret the marginal effects of the explanatory variables. Other studies used nonlinear regression methods to investigate voting bias in this competition making the interpretation of marginal effects challenging (see [The second method uses ordinary least squares (OLS) to estimate parameter estimates with the dependent variable represented as the bias calculation, as shown by Eqs ing (see  for a goWe now briefly discuss the bivariate correlations between some variables to investigate the relationships between voting bias and established in-group factors. We then present the results for our three hypotheses.CDjk) and geographical distance are negatively correlated with voting bias and statistically significant across all points values, separately. This finding indicates that voting bias decreases on average as the cultural or geographical distances between a voter and a player increases. Likewise, nationality, club, league, and being from a neighboring country are positively correlated and statistically significant with voting bias. This result indicates that increasing similarity between these characteristics increases voting bias on average. These relationships become even more pronounced when correlations are calculated based on individual points awarded , providing further evidence to warrant the specification of regression models using individual points awarded.We use a player-specific fixed-effect regression model to investigate the presence of voting bias. Two panels were constructed for investigating the player fixed-effect model: one is constructed by players with at least three nominations from 2010 to 2016 ; one is constructed by players with at least four nominations during the same period . The two panels show similar results. The adjusted R-square is approximately 75% for all ten models (five for each panel), indicating that performance and players’ heterogeneity explain a high proportion of the variability in the votes received. The statistical value of rho shows that variances due to individual heterogeneity are approximately 60% to 70%. This finding shows that something other than wins, goals, and assists can be attributed to the voting results.P < 0.0001), further providing statistical evidence of the potential for voting bias in the selection of players (and support for our first hypothesis). The analysis also shows that goals per game is the most significant of the three-performance factors utilized. Goals per game is positive  and statistically significant (P < 0.10) across both panels. Assists per game has a positive sign which corresponds to our hypothesis but is not statistically significant (0.15 < P < 0.10). Interestingly, the coefficient for the percentage of games won indicates that a higher percentage of games won leads to a lower percentage of the total votes awarded in any given year. The negative sign is not consistent with the expectation that a higher percentage of games won would lead to a higher percentage of votes received. An explanation is that this factor is not closely related enough to an individual players’ performance, such as goals and assists, since the percentage of games won is the entire team’s performance. For this reason, we do not use this performance measure in other estimations.The premise that there is no individual player-specific heterogeneity is firmly rejected in all models  due to the nature of the calculation of voting bias used within this study. Therefore, as shown, we have selected to control for the number of points awarded by running regression models for 5, 3, and 1 points awarded separately. Results from the first set of regression models for voting bias are presented in P < 0.001, P < 0.01 and P < 0.05 across points 5, 3 and 1 respectively; GLOBE: P < 0.001, P < 0.01 and P < 0.01 across points 5, 3 and 1 respectively). Likewise, if a voter and a player come from neighboring counties, voting bias is positive and significant across all points and data sets, but to a lesser extent for 1 point awarded. The regression models demonstrate consistent results using both Hofstede and GLOBE data sets. Model one and seven are considered the baseline models containing only the control variables. As shown, voter type and year both have significant impacts on voting bias. Interestingly, media voters have a significantly lower voting bias than captain voters (and coaches). Coaches also tend to have a lower voting bias than captains on average. However, their coefficients are not significant. Nationality is positive and statistically significant across all models indicating its significant role in voting bias in the competition. Interestingly, we also find that physical geographical characteristics are statistically significant with voting bias. As geographical distance decreases between a voter and player, voting bias is positive and significant across models using both Hofstede and GLOBE data sets . This finding may indicate that captains are trying not to disclose blatant voting bias, given their close association with teammates. When voting for players within the same league, results demonstrate positive and statistically significant voting bias across all points awarded.Interestingly, not shown in Based on these findings, we find sufficient evidence to support our first hypothesis that there exists voting bias in the Award, which can be attributed to the factors discussed.Regression models were developed for our second hypothesis regarding the affect of cultural similarity on voting bias in the Award. These models examine the relationships between the variables defined in section 3.2 for both Hofstede and GLOBE data sets. Model 1 and 6 establish a baseline with only control variables, while independent variables are integrated step-wise in the subsequent models. Models 2 to 5 and 7 to 10 test our second hypothesis using an independent variable for cultural distance, cultural clusters, and voter collectivism.CDjk) are negative and statistically significant at the 1% level except for the case of 1 point awarded for both data sets . These results are consistent when controlling for players and voters with the same nationality. Likewise, we find evidence that cultural clusters (CCjk) are positive and significant . This finding demonstrates a higher degree of voting bias when awarding points to players from the same cultural society (the ‘in-group’) than awarding points to different cultural societies (the ‘outside group’). We also find that voting bias across cultural clusters (or ‘societies’) with positive and statistically significant coefficients on all points awarded.Our findings support the hypothesis that an increase in cultural distance leads to a decrease in voting bias. All coefficients for cultural distance (VCj) would positively influence voter bias. As shown in P = 0.54) but significant for one point awarded (estimated coefficient of 0.17 and P = 0.011). For the GLOBE data set, both types of collectivism are insignificant for 3 and 1 points awarded. This finding could be due to the Hofstede data set being three times larger than GLOBE, thereby providing stronger evidence of voter collectivism. Interestingly, for the GLOBE dataset, the coefficient for collectivism II (in-group collectivism) consistently demonstrates a stronger influence on voting bias than collectivism I  through various models. When both forms of collectivism are run concurrently in the same model, collectivism I becomes insignificant (estimated coefficient of 0.05 and P = .31) and collectivism II remains positive and significant (estimated coefficient of 0.18 and P = 0.006).With hypothesis 2, we also propose that higher voter collectivism (P < 0.01) for all points awarded. This further supports our hypothesis that as voters and players become more culturally diverse, especially with respect to in-group collectivism, voting bias decreases on average.Lastly, models 5 and 10 further test the individual effects of specific cultural dimensions from both Hofstede and GLOBE on voting bias using . We findAs shown previously in Despite some inconsistency for voter collectivism at lower points awarded, we believe our findings provide sufficient evidence to support our second hypothesis that cultural factors are positively associated with voting bias in the Award.CCjk x impartiality Imj) that is expected to be negative and significant, which implies that the level of voting bias in countries of cultural clusters diminishes as impartiality Imj  increases. As shown in Although countries in cultural clusters exhibit a higher degree of voting bias than countries that are not in the cluster, they are expected to do so to a lesser extent as impartiality increases across countries within cultural clusters , 55. UsiThe coefficient for impartiality is insignificant using Hofstede across all points awarded but is significant and negative using the GLOBE data set for 5 and 1 points awarded. This means that as the quality of government improves, there is some evidence to demonstrate that voting bias decreases on average. However, the effect of a voter and a player being in the same cultural cluster is stronger, not weaker, as the quality of government of the voter’s country increases. We find consistent results when using nationality within the interaction term instead of cultural clusters. In accordance with our third hypothesis, we would anticipate witnessing some evidence of impartiality in voting bias for voters and players who share the same nationality, but this is not the case again.Based on these findings, there is insufficient evidence to support our final hypothesis of greater impartiality regarding cultural voting bias . We find the opposite, with evidence of a moderating effect of cultural and national influences on impartiality.In this paper, we examine how cultural factors and established in-group factors impact voting bias in one of the world’s most prominent sporting awards. Our study and results constitute the most comprehensive study on voting bias in the Award and are robust, using both Hofstede and GLOBE datasets for cultural dimensions.Consistent with previous literature on voting bias in awards and social identity theories, we find that nationality, the league, and the club are all important determinants of the voting bias in the Award. We add to existing research by showing that voter-player similarity in cultural distance, cultural clusters, and collectivism strongly influence voting bias. Furthermore, we find that countries with a greater diversity of ethnicity, language, and religion, demonstrate lower voting bias. We also find an increase in voting bias between voters and players of neighboring countries and between voters and players whose capital cities are in close geographical proximity. However, we found no evidence of impartiality in voting bias for voters and players that share the same cultural cluster or nationality.In terms of voter type, voters from the media have the least amount of voting bias for all points awarded compared to captains and coaches, and this difference is consistently significant. Captains, on the other hand, have the greatest relative degree of voting bias compared to coaches or media, but this degree is only significant for the 5 points awarded. Captains are relatively closer to players in the context of voting, and this supports the theory that the proximity of the relationship through in-group and cultural factors may play an important role in voting bias.Given the propensity for voting bias in awards, our research highlights the importance of having awards provide criteria concerning what constitutes quality. For the Award this would include total goals, goals per min, total assists, pass completions, player of the match, and saves. Such criteria could counter bias by better grounding, driving, and assessing voting choices. Also, if an award is relatively transparent concerning the voter-player factor similarities, as was the case with the Award, then this has two potential impacts. First, without such transparency, the award is more likely to escalate the effects of in-group bias while inviting irresponsible, naïve, and foolish voting decisions. Second, the information from such transparency could be used to analyze how votes were cast, like our study. Award organizers could use the analysis to identify and adjust any highly inappropriate bias while reporting and declaring the levels and types of bias exhibited. Such transparency and reporting would help make voters more aware of the propensity and impact of bias. Also, like studies of fake news that expose readers to simple accuracy reminders before consuming news to enhance truth discernment in participants’ , similarFurthermore, our analysis of voting bias also provides a logic to help design awards where voters are required to only vote on candidates who are sufficiently dissimilar according to one or more in-group factors. For example, the NBA altered the voting process for its MVP awards in 2017 by removing media representatives with broadcasting ties that were closely associated with individual teams in a primary role . Today, Finally, an important limitation of our study, which is also an opportunity for future research, is to control for voter taste for players who play in certain positions and play for the prestigious clubs and national teams. For player position, voters prefer forwards and midfielders over defenders and goalies, as creating and scoring goals in football is typically more entertaining and appreciated than tackling and saving shots. Similarly, there are halo effects  where thS1 Appendix(DOCX)Click here for additional data file.S1 Data(DOCX)Click here for additional data file.


Different copolymers were assessed, and the carrier with the highest encapsulation efficiency (EE) and drug loading capacity (DLC) was selected for further elaboration of nanocomposite in situ gel formulations. Next, the sol-to-gel transition behavior of HPC as a function of K2SO4 concentration in the aqueous solution was investigated by microcalorimetry and dynamic oscillatory rheology, and the optimal formulation capable of forming a physical gel under physiological conditions was determined. Finally, injectable nanocomposite hydrogels comprising cannabidiol were fabricated, and their drug release profile and cytotoxicity against human tumor cell lines were evaluated. The in situ gels exhibited prolonged drug release over 12 h, controlled by gel erosion, and the cytotoxicity of formulated cannabidiol was comparable with that of a free drug.Cannabidiol (CBD) is a natural terpenophenolic compound with known pharmacological activities, but the poor solubility of CBD in water limits its widespread use in medicine and pharmacy. Polymeric (nano)carriers demonstrated high potential for enhancing the solubility and therapeutic activity of lipophilic drugs such as CBD. Here, we report the elaboration of a novel hydroxypropyl cellulose (HPC)-based in situ gelling formulation for controlled delivery of CBD. In the first stage, nanosized polymeric micelles from poly(ethylene oxide)- Hydrogels are a unique class of polymeric materials capable of retaining large amounts of water while maintaining their integrity and shape ,2. In faRecently, research on hydrogels for biomedical applications has focused on stimuli-responsive systems that can form gel at physiological conditions and thus reduce the risks involved in the surgical implantation of conventional hydrogels . In thissol-gel) close to physiological temperature [sol-gel of cellulose derivatives and thus achieve gelling material at the desired temperature of 37 °C. The first approach is based on chemical modification, where synthetic (co)polymers or units are covalently attached to the polysaccharide macrochains. For instance, Miao et al. prepared a thermoresponsive hydrogel via click reactions between alkynyl-functionalized hydroxypropyl cellulose and azide-modified poly(N-isopropylacrylamide-co-hydroxyethyl methylacrylate polycaprolactone) [sol-gel of pure HPC is 44 °C. Another study revealed that the reaction of HPC with N-methyl carbamoylimidazole can also decrease the LCST of HPC, and Tsol-gel is dependent on the methylcarbamate degree of substitution [sol-gel of temperature-responsive cellulose derivatives [Polymers from natural sources such as polysaccharides  and proteins  have been widely used for fabricating injectable hydrogels ,12. Natuperature . For exaperature . Contrarperature . Generallactone) . This sytitution . It shouivatives ,17. By tb-P(CyCL-co-CL) micelles was developed, and its antiproliferative potential against human breast cancer MCF-7cells was tested in a comparative way vs. a free drug in order to enable sustained CBD release after application in the surgery area of the primary tumor and the dissected lymph nodes. In addition, the biocompatibility of the developed nanocomposite gel carriers was investigated on normal fibroblast cells and was shown to be devoid of significant cytotoxic potential. To get a physical hydrogel at physiological temperature, the Tsol-gel of HPC was decreased by adding K2SO4 to the polymer solution. At a salt concentration of 0.15 molL−1, the sol-gel transition point of the system was adjusted to approximately 35 °C, as confirmed by microcalorimetry and dynamic rheological measurements. Cannabidiol is a natural terpenophenolic compound with proven pharmacological activities such as anti-inflammatory, antioxidant, analgesic, antidepressant, etc. . One of Nanosized micelles comprising a hydrophobic PCL-based core and a hydrated PEO shell were formed via the aggregation of amphiphilic PEO-b-P(CyCL-co-CL) and PEO-b-PCL diblock copolymers in water and then loaded with CBD . −1. The copolymer concentration was approximately an order of magnitude higher than the critical micelle concentrations (CMC) of PEO-b-P(CyCL-co-CL) and PEO-b-PCL, as determined in our previous study [PEO-b-PCL block copolymers have been commonly used for biomedical applications and fabricating nanocarriers intended for controlled release of hydrophobic drugs . The incus study . Next, th), and zeta potential of the blank and CBD-loaded micelles  and PEO-b-PCL diblock copolymers demonstrated relatively high DLC and EE, which were dependent on the copolymer composition and copolymer/drug mass ratio (113-b-P(CyCL1-co-CL27)28 vs. PEO113-b-PCL29). These results confirmed our hypothesis that the cinnamyl groups enhance the compatibility between the micellar core and CBD and thus improve the loading capacity of the carrier. On the other hand, a dependence was found between the EE and DLC of the two cinnamyl-modified copolymers and the length of the PCL chain (degree of polymerization 27 vs. 12), indicating that the more hydrophobic copolymer could encapsulate a larger amount of CBD. The highest DLC values for the three investigated systems were obtained at the lowest copolymer/drug mass ratio (5:1), while the highest EE values were calculated at the highest copolymer/drug mass ratio (10:1).The carriers based on PEO-ss ratio . DefinitAs mentioned before, HPC is a temperature-responsive natural polymer possessing a lower critical solution temperature of about 44–45 °C, which is above the body temperature (37 °C) . However2SO4 to decrease the sol-gel transition temperature (Tsol-gel) of HPC in distilled water was investigated in detail. The measurements were conducted at an oscillatory frequency (f) of 1 Hz and a strain amplitude (γ0) of 0.001, which is inside the linear viscoelastic regime (−1) at 25 °C, and the physical gelation of different systems as a function of temperature was monitored. At low temperatures, the samples exhibited typical polymer solution behavior. The loss modulus (G″) was higher than the storage modulus (G′), indicating that the viscous component was predominant over the elastic one. Above the given temperature, the two moduli tended to increase, with a more pronounced effect for G′. At a certain point, G′ and G” crossed (the sol-gel transition point), and then the curves acquired the typical pattern for gels where G′ > G″  was added to the HPC solution. Adding K2SO4 also affected, to some extent, the elastic properties of hydrogel. As can be seen from the data in This assumption was supported by experimental results revealing a linear decrease in T samples . The higanalyses . Indeed,2SO4 concentration of 0.15 molL−1 was chosen for our further experiments.The polymer concentration, ranging from 10 to 15 mass%, did not significantly influence the sol-gel transition point, indicating that the gelation under the reported conditions was predominantly a temperature-driven process. On the other hand, the increase in HPC concentration yielded hydrogel with notably enhanced elastic properties . Regardi2SO4, and nanoformulated PEO113-b-P(CyCL1-co-CL27)28/CBD in water at 25 °C and subsequent heating to 37 °C (−1) and micelles (1 gL−1) were kept constant. As discussed earlier, the physical gel was formed as a result of hydrophobic interactions between pendant hydroxypropyl groups in the polysaccharide chains. The presence of SO42− anions in the system facilitated this process and decreased the sol-gel transition temperature below the body temperature. Adding drug-loaded micelles had only a minor effect on the rheological properties of HPC/K2SO4 systems.Nanocomposite HPC in situ hydrogels, containing CBD-loaded micelles, were fabricated by dissolving HPC, Kto 37 °C . Three dsol-gel, but it contributed to the increase in the elastic modulus of the material. Indeed, G′ of the nanocomposite hydrogel was more than two times higher than G′ of the blank gel obtained at the same conditions (b-PPO-b-PEO micelles with a rigid core [b-P(CyCL-co-CL) micelles, the PCL-based core is rigid at 37 °C, and we hypothesized that this feature of the nanocarriers is the main factor in increasing the stiffness of the material. Having in mind that the mass ratio of HPC/copolymers in the studied sample was 150:1, we prepared an in situ gel with five times more concentrated sample of CBD-loaded micelles and then performed rheological measurements (b-P(CyCL-co-CL) micelles. In fact, the G′ values at 1 Hz for pure HPC hydrogel and nanocomposite HPC hydrogels, containing 1 and 5 gL−1 CBD-loaded micelles, were 940, 2165, and 4360 Pa, respectively.Dynamic rheological studies confirmed that the elaborated dosage forms are liquid at room temperature and physical gels at 37 °C, respectively a. The vanditions b. Such rgid core . In the urements b. The reIt should be noted that the transition from viscous liquid to hydrogel was completed in approximately 10 s when the sample was heated on the rheometer plate from 25 to 37 °C . During In general, the rheological behavior of the developed HPC-based drug formulations fulfills one of the most important requirements for injectable hydrogels—the formulation is viscous at room temperature and forms an elastic gel in situ at body temperature. This characteristic, together with the significantly improved solubility of CBD in aqueous media (with the aid of micelles), makes the nanocomposite HPC in situ gels a promising platform for developing advanced injectable forms of CBD with specific locoregional antineoplastic activity.−1 of CBD-loaded PEO113-b-P(CyCL1-co-CL27)28 micelles (polymer/drug mass ratio 10:1), were used. As evident from the released profiles shown in −1) showed a slower cannabidiol release compared to the analogous composition with a lower micellar content (1 gL−1). A comparison of the drug release profiles to the gel dissolution profiles showed a good correlation between the two processes. This indicates that the cannabidiol release mechanism is controlled to the greatest extent by the gel erosion process. Both the erosion of the gel and the release of cannabidiol are slower in the sample with the higher micellar fraction. This fact can be explained by the reinforcing effect of the micelles on the gel structure. These observations correlate well with the results from dynamic rheological studies, where the higher storage modulus is associated with a higher micellar content in the gel matrix , containing 1 and 5 gLtrix see b.50 concentrations thereof are shown in 50 = 10.7 µM). The two CBD formulations (micelles and nanocomposite in situ gels) showed slightly higher IC50 values as compared to the free drug  was donated by Hercules Inc., Aqualon Division, Wilmington, NC, USA. Potassium sulphate (99%), ethanol (99.5%), methanol (≥99.8%), and acetone (99%) were purchased from Sigma-Aldrich via FOT, Sofia, Bulgaria, and used as received. Cannabidiol  was donated by PBG GLOBAL LTD., Sofia, Bulgaria. The block copolymers were synthesized as described elsewhere . Synthet−1) at ambient temperature for 30 min. Subsequently, the organic solvent was evaporated under vacuum at 40 °C to afford stable micellar solutions with a concentration of 1 gL−1.The polymeric micelles were prepared by the solvent evaporation method. Briefly, 10 mg of each copolymer were dissolved in 5 mL of acetone, and the solutions were added dropwise to 10 mL of deionized water at 25 °C under stirring. The resulting solutions were stirred vigorously (800 min−1) in ethanol was added dropwise to the aqueous micellar solutions (15 mL) at copolymer/CBD mass ratios of 10:1, 7:1, and 5:1. After stirring for 30 min, the ethanol was removed under vacuum at 40 °C. The micellar dispersions were filtered (0.45 µm), and the filter was rinsed with methanol. The amount of non-encapsulated CBD in the collected filter fraction was determined by UV-vis measurements (λ = 274 nm) using a calibration curve in methanol (A solution of CBD (1 gLmethanol . The encw/v) were prepared by dissolving HPC  into 4 mL of pure water or aqueous solutions of K2SO4  under stirring at room temperature. After stirring for 20 min, the viscous solutions were kept overnight at room temperature (25 °C) before measurements. HPC hydrogels  and CBD-loaded micelles (1 g/L−1) under stirring at room temperature. After stirring for 20 min, the viscous solutions were kept overnight at room temperature before measurements. Nanocomposite formulations were prepared by dissolving HPC (0.6 g) in 4 mL of an aqueous solution of K−1. The ultraviolet-visible absorption spectra were recorded on a UV-vis spectrophotometer  using quartz cells with a path length of 1 cm. Calorimetric measurements were conducted using a nano-differential scanning calorimeter . Approximately 0.6 mL of sample solution and an equal amount of reference fluid (deionized water) were hermetically sealed into the sample and reference cells. DSC curves were recorded in the temperature range of 15 to 90 °C at a rate of 1 °Cmin−1. Dynamic rheological measurements were conducted with a HAAKE MARS 60 rheometer . The tests were performed with a parallel plate geometry  in controlled deformation (CD) mode. Three runs of each sample were conducted. Prior to the temperature sweep measurements, amplitude and frequency sweep tests were made to establish the linear viscoelastic range for HPC gels. The gelation process was studied in oscillation-temperature sweep experiments. Storage and loss moduli were determined at constant deformation and frequency  in a given temperature range (25–45 or 35–55 °C). The sample were equilibrated for 60 s at the given temperature before recording a data point. The hydrodynamic diameter of micelles was determined by using Zetasizer NanoBrook 90Plus PALS , equipped with a 35 mW red diode laser (λ = 640 nm) at 25 °C and a scattering angle of 90°. The electrophoretic light scattering measurements were conducted on the same instrument at a scattering angle of 15° and 25 °C. The phase analysis light scattering (PALS) method was applied for measuring the electrophoretic mobility. Atomic force microscopy (AFM) height images were obtained with a Bruker Dimension Icon microscope  in peak force tapping mode exploiting silicon nitride cantilevers with a spring constant of ~0.4 NmTo evaluate the cannabidiol release profiles of optimally prepared nanocomposite in situ gels, a membrane-less diffusion method was utilized as described elsewhere  with sli2 atmosphere. CCL-1 cells were maintained following the recommendations of ISO 10993-5, Annex C  [The in vitro cytotoxicity of elaborated empty micelles and nanocomposite in situ gels prepared thereof was evaluated on normal murine fibroblasts , while the antiproliferative activity of free or formulated nanocomposite in situ gels cannabidiol was assessed in malignant human tumor MCF-7 cell line (breast cancer adenocarcinoma) obtained from ATCC, Manassas, VA, USA. The cells were cultivated according to the protocol instructions of the supplier and incubated under standard conditions at 37 °C in a 5% humidified CO9, 2017) . 5. After 24 h of incubation, cells were treated with serial dilutions of the tested formulations with respect to cannabidiol concentration. Following an exposure time of 72 h, sterilized MTT substrate solution (5 mg/mL in PBS) was added to each well, and the plates were further incubated for 1–4 h, allowing the formation of purple insoluble formazan crystals. The latter were dissolved in an isopropyl alcohol solution containing 5% formic acid, and the absorbance was measured at 550 nm. The collected absorbance values were blanked against MTT and isopropanol solutions and normalized to the mean value of the untreated control (100% cell viability). The experimental data were processed using a non-linear regression analysis algorithm, semi-logarithmic “dose-response” curves were constructed, and the corresponding half-inhibitory concentrations (IC50) were calculated.The in vitro cytotoxicity of the elaborated nanocomposite in situ gels was evaluated using a standard MTT method with minor modifications . The metb-P(CyCL-co-CL) diblock copolymers played a key role in achieving a water-soluble form of the lipophilic drug CBD. Embedding CBD into nanosized micellar carriers enabled the fabrication of a homogeneous viscous mixture of the temperature-responsive HPC, K2SO4, and nanoformulated CBD, which then formed a reversible physical gel. The salting-out effect of K2SO4 was exploited to tune the sol-gel transition of the HPC-based aqueous system at near body temperature. Thus, the transition from a liquid form to a gel at approximately 35 °C was completed with a K2SO4 concentration of 0.15 molL−1. Nanocomposite gels released the encapsulated cannabidiol in a controlled manner over a period of 10–12 h, which depends on the erosion time of the polymer matrix. Tests with non-malignant fibroblast CCL-1 cells revealed that the polymeric carriers themselves are not cytotoxic, while the CBD-loaded HPC hydrogels exhibited pronounced activity against malignant MCF-7 human tumor cells. The elaborated in situ gel formulation may have beneficial advantages when applied in liquid form to the surgery area of the primary tumor and its metastatic spread to lymph nodes, liver, bones, etc.A novel in situ gelling formulation for controlled delivery of CBD based on the natural polymer hydroxypropyl cellulose was developed. Nanosized polymeric micelles of PEO-


Those with cirrhosis who develop colorectal cancer (CRC) are an understudied group who may tolerate treatments poorly and are at risk of worse outcomes. This is a retrospective cohort study of 842 individuals from Ontario, Canada, with a pre-existing diagnosis of cirrhosis who underwent surgery for CRC between 2009 and 2017. Practice patterns, overall survival, and short-term morbidity and mortality were assessed. The most common cirrhosis etiology was non-alcoholic fatty liver disease (NAFLD) (52%) and alcohol-associated liver disease (29%). The model for end-stage liver disease score (MELD-Na) was available in 42% . Preoperative radiation was used in 62% of Stage II/III rectal cancer patients, while postoperative chemotherapy was used in 42% of Stage III colon cancer patients and 38% of Stage II/III rectal cancer patients. Ninety-day mortality following surgery was 12%. Five-year overall survival was 53% . Those with alcohol-associated cirrhosis  had lower survival than those with NAFLD. Those with a MELD-Na of 10+ did worse than those with a lower MELD-Na score . This study reports poor survival in those with cirrhosis who undergo treatment for CRC. Caution should be taken when considering aggressive treatment. Both liver cirrhosis and colorectal cancer are expected to rise over the next several decades, especially among young adults ,2,3. ThoTreatment of colorectal cancer in those with an existing diagnosis of cirrhosis can be a challenge. Curative intent treatment typically requires major surgical resection and may include liver-toxic chemotherapy ,5. PreviDespite the increasing incidence of both cirrhosis and colorectal cancer, there have been few contemporary studies assessing outcomes among this complex and unique group. Thus, the objectives of this study were to (1) determine the proportion of patients who receive guideline-recommended cancer treatments (such as radiation and chemotherapy); (2) determine the overall survival; (3) determine the associations between cirrhosis etiology and/or severity and survival among a cohort of patients with cirrhosis and CRC.This is a retrospective population-level study of all individuals with cirrhosis who underwent surgery for colorectal cancer in Ontario, Canada, from January 2009 to December 2017 with outcome events followed until the end of 2020. This study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines .This study uses routinely collected healthcare datasets stored at ICES. These datasets include health administrative data that are routinely generated upon the delivery of a healthcare service to an individual, as well as demographic and census data. The datasets were linked at the individual level using a unique encrypted identifier and analyzed at ICES .Individuals with incident or prevalent cirrhosis were identified using a previously validated algorithm . The algPatient demographics were derived and included age at the time of surgery, sex, and socioeconomic status. Co-morbid illness was defined using the Charlson co-morbidity index. Specific pre-existing comorbidities were identified in patients based on ICES-validated definitions ,25,26,27Surgery type was categorized as resection with anastomosis, resection without anastomosis (permanent ostomy), or resection with anastomosis and proximal diversion based on the fee code that was billed in OHIP at the time of surgery . SurgicaThe primary outcomes were 5-year overall survival outcome and overall survival as a time-to-event outcome. Secondary outcomes included the receipt of guideline-recommended neoadjuvant and adjuvant therapies as described in well-established clinical practice guidelines ,5.Other short-term outcomes included in-hospital mortality, 90-day mortality, intensive care unit (ICU) admission, hospital and ICU length of stay, 90-day readmission and 90-day emergency department (ED) visit, and hepatic decompensation . These dCounts and proportions were calculated for categorical variables and means with standard deviations or medians with interquartile ranges for continuous variables. We used chi-square statistical tests to compare categorical proportions, one-way analysis of variance to compare means, and Kruskal–Wallis test as a non-parametric approach to compare median values between cancer-type groups. For cells with small numbers  ranges are presented to protect the anonymity of the patient population, as required by ICES.Postoperative outcomes were described according to cancer type along with counts and proportions for categorical outcomes and means with standard deviations or medians with interquartile ranges for continuous outcomes. In-hospital and 90-day mortality was further elucidated by the MELD-Na score. Five-year survival was evaluated using Kaplan–Meier curves and stratified according to cancer type and stage. Predictors associated with postoperative mortality during follow-up were assessed using Cox proportional hazards models. Patients were followed from the time of surgery until death or 31 December 2020. Predictors were selected a priori and evaluated for violation of the proportional hazards assumption using Schoenfeld residuals. We performed a sensitivity analysis by repeating the multivariable Cox models for predictors of postoperative mortality in a subset of the cohort that had an available MELD-Na score and included MELD-Na as a predictor of interest. We also performed a sensitivity analysis, excluding those who died within 90 days of surgery.p-value < 0.05. All data were prepared and analyzed using the SAS Enterprise Guide, Version 7.1 . Results were considered significant at n = 441, 52%), followed by ALD , viral hepatitis , and autoimmune or other . A small number had a history of hepatic decompensation . The MELD-Na was available for 353 individuals (42%), with a median score of 9 (IQR 7–11). Cancer stages included Stage I disease , Stage II disease , Stage III disease , and Stage IV disease . Most individuals underwent elective surgery . In those with colon cancer (N = 696), the most common procedure was resection with anastomosis , followed by resection and permanent ostomy . Few individuals with colon cancer underwent anastomosis and proximal diversion . Those with rectal cancer (N = 146) most commonly had a resection with a permanent ostomy  or resection with anastomosis and proximal diversion . Few individuals underwent resection and anastomosis without diversion .A total of 842 individuals with cirrhosis underwent surgery for colorectal cancer, including 696 individuals with colon cancer and 146 with rectal cancer . DemograIn those with Stage III colon cancer, approximately half  had a medical oncology assessment, with 42% (90/213) ultimately receiving adjuvant chemotherapy. In those with locally advanced rectal cancer , 70% (62/89) had a radiation oncology assessment, with 62% (55/89) receiving preoperative radiation. Similar to Stage III colon cancer, about half  of those with locally advanced disease had a medical oncology assessment and 38% (34/89) ultimately received adjuvant chemotherapy. n = 219/353, 62%), with few having a score >20 . The 90-day mortality in those with a MELD-Na <10 was 6.8% vs. 22% in those with a MELD-Na >10 (p < 0.001) (Short-term outcomes are presented in < 0.001) .The 5-year overall survival for the cohort was 53%. Cox proportional hazards regression was completed for all individuals in the cohort  and was Cox proportional hazards regression was also completed for the subgroup with MELD-Na score available at the time of surgery . Those wThe present study reports practice patterns and outcomes in those with cirrhosis who develop colorectal cancer and undergo surgical resection. The 5-year overall survival for the cohort was 53%. Cirrhosis etiology was associated with overall survival, while MELD-Na score was predictive of increased 90-day mortality. A number of other major short-term complications were common, including 90-day mortality (12%).The present study is the largest and most contemporary report of outcomes in those with cirrhosis who develop colorectal cancer and receive surgery. Several older studies have reported long-term survival ,31,32,33p = 0.082). This association persisted even after adjusting for MELD-Na in those with a score available. The reasons for this are not immediately clear from the data but could relate to individuals with ALD having a more advanced liver dysfunction that is not able to be captured using MELD alone such as the degree of ascites and hepatic encephalopathy. Further, individuals with ALD cirrhosis have historically included a higher proportion who are vulnerable due to their social determinants of health, which may influence the ability of patients with ALD to access and engage in care. An interesting finding from this work is the differences in outcomes based on the etiology of cirrhosis. Those with ALD had a worse survival compared with those with NAFLD  compared to that reported for all comers in Canada (65%), based on previous publications . The CanThis study has several strengths. Due to the relative scarcity of individuals with both a diagnosis of cirrhosis and colorectal cancer, a population-based approach allowed for the inclusion of a large number of individuals. The identification of those with cirrhosis was made using a previously validated algorithm which ensured a low risk of misclassification or inappropriate inclusion. We also identified those with colorectal cancer using the Ontario Cancer Registry, which is highly accurate. For these reasons, there was a low risk of missing individuals with pre-existing cirrhosis who developed colorectal cancer. The type and extent of treatment were determined using well-established sources, while the outcomes were determined using previously validated approaches. As the data for this study were ascertained using linked administrative databases within a single-payer universal healthcare system, loss to follow-up was minimal.Despite these strengths, several well-described limitations of population-based studies exist within this study . PertinePatients with cirrhosis who develop colorectal cancer and undergo surgical resection infrequently receive guideline-recommended treatment, have poor short-term outcomes, and have poor overall survival. Further, compared to the general population, the stage of the disease is less likely to be predictive of long-term survival, especially in those with rectal cancer. We found liver-related factors, including ALD and MELD-Na > 10, to be associated with survival. This information will assist healthcare providers in having detailed discussions with these patients and their caregivers, allowing for enhanced awareness and education pertaining to the anticipated challenges associated with treatment.


In this paper, taking the generalized synchronization problem of discrete chaotic systems as a starting point, a generalized synchronization method incorporating error-feedback coefficients into the controller based on the generalized chaos synchronization theory and stability theorem for nonlinear systems is proposed. Two discrete chaotic systems with different dimensions are constructed in this paper, the dynamics of the proposed systems are analyzed, and finally, the phase diagrams, Lyapunov exponent diagrams, and bifurcation diagrams of these are shown and described. The experimental results show that the design of the adaptive generalized synchronization system is achievable in cases in which the error-feedback coefficient satisfies certain conditions. Finally, a chaotic hiding image encryption transmission system based on a generalized synchronization approach is proposed, in which an error-feedback coefficient is introduced into the controller. Chaos is a unique nonlinear dynamical phenomenon with the properties of ergodicity, initial sensitivity, and the long-term unpredictability of motion trajectories ,2,3,4. IGeneralized synchronization is the gradual convergence of the trajectory curves of two chaotic systems to a time-independent transformation relationship over time; that is, a functional relationship is determined between the state of the driven system and the state of the responding system, and the synchronization of the driven and responding systems is achieved by this functional relationship, which can be deterministic or nondeterministic ,20,21,22The paper is organized as follows: The generalized synchronization theoretic of discrete chaotic systems and the stability principle of error systems are analyzed in In our study of chaotic control problems, it is more important to convert the problem of chaotic synchronization into the analysis of system errors. The main idea is to consider the difference in the state between the drive and response systems, that is, the synchronization error of the system. Once a reasonable controller has been designed by parameter changes to make the system error asymptotically stable at the origin point, then the two systems can be considered synchronized with each other. Firstly, the mathematical model of generalized chaotic synchronization is proposed in this paper and described, as follows.Definition 1.Consider two n-dimensional nonlinear dynamical systems, and describe them using the following equations:where , , and as well as are n-dimensional nonlinear functions, and is an n-dimensional input control function. If the selectable function is applied such that , and thus , then it can be translated into the study of the error system , for which , and therefore . In this case, the drive system and response system can reach a generalized synchronization.Theorem 1.Define an invertible transform ;consequently, there is an incorporated error-feedback coefficient .Where the feedback coefficient satisfies the condition , it can enable the progressive stability of the zero solution of Error Equation (3) of the system, which is represented as follows:Because the zero solution of Equation (3) is gradually stable, by introducing a reasonable feedback coefficient  and response system (2), a nonlinear error system  Chaotic system (4) is progressively stable if the modulus of all eigenvalues of matrix A is not more than 1;(2) TPA − P = −Q) has a unique positive solution (P), system (4) is asymptotically stable.In case there is a matrix (Q > 0), so that the Lyapunov equation (A.Given Proof of Lemma 1(1). Set A have a value of modulo less than 1, all the eigenvalues of matrix Because all the eigenvalues of matrix Proof of Lemma 1(2). Set Furthermore, Lemma 1, the determination processes for the stability of nonlinear discrete systems can be given through Lemma 2, which is described as follows:Based on the proof processes for the stability of linear discrete systems as related in Lemma 2.For a nonlinear discrete system  be the equilibrium point of the proposed system. Provided that the scalar function concerning satisfies the following:(1) ,(2) .then is progressively stable.Proof of Lemma 2.Lemma 1. Moreover, For condition (1), let Thus, the proof of condition (2) is complete. Based on the above, it is concluded that nonlinear system (4) is asymptotically stable at the origin point.Lemma 1 and Lemma 2, the proof of Theorem 1 can be obtained, which is as follows:Thus, having proved Proof of Theorem 1.According to Equations (1) and (2), Equation (3) can be calculated as follows:Then, Equation (9) can be simplified as the following equation:Denote the scaled function of the nonlinear error system  is represented by a = 6.53, and after 1000 iterations, the Lyapunov exponents of system (12) are 0.7296, 0.1650, and 0.6226, which are all positive; thus, system (12) is a hyperchaotic system.A new 3D discrete chaotic system (12) is proposed in this paper, which is described as follows:Based on 64-bit Matlab software and double-floating-point representation, the initial values of the state variables of the chaotic system are set differently. The output chaotic sequences and their autocorrelation are shown in Theorem 1, the system errors are calculated as follows:Let us assume that the system of responding systems of the drive system (12) is as follows:Then, the error system equation can be expressed as follows:Let the control function be represented by Equation (16):Thus, system (14) can be simplified to expression (17):Let the Lyapunov exponent function of system (17) be represented by the following expressions:Lemma 1. The zero solution of error system (13) is asymptotically stable so that generalized chaotic synchronization can be achieved. In summary, the incorporation of the error-system-feedback coefficient  is a hyperchaotic system because the four Lyapunov exponents are positive.High-dimensional chaotic systems have more complex dynamics than low-dimensional chaotic systems; thus, they are better able to resist the degradation of dynamics caused by the limited accuracy of computers. In this paper, a new 6D discrete chaotic system (21) is constructed by expanding on system (12), which can be presented as follows:Based on 64-bit Matlab software and double-floating-point representation, for different initial values of the state variables, the output of chaotic sequences and their autocorrelations are shown in Let the corresponding system of driving system (21) be considered as follows:Lemma 2:Equation (23) is obtained from The equation of the error system can then be expressed as follows:Let the control functions be calculated as follows:Then, system (24) can be expressed as follows:Consider the Lyapunov exponent functions of system (25) as follows:Lemma 2, when the parameter Obviously, according to A be expressed as follows:Let the invertible transformation function be k changes for systems (21), (22), and (24) are shown in Moreover, set the initial conditions of the proposed driving system (21) as The framework diagram of the proposed encryption and decryption transmission system constructed in this paper is shown in The proposed system is designed for the encrypted transmission of digital images with pixel matrix values of The output sequences  image was used as an example for the encryption and decryption processes, and the results of the operation are shown in m × n, it takes about As can be seen from the encryption process in Security analyses of the transmission system for the proposed digital image encryption and decryption based on generalized chaotic synchronization are performed in this paper, which consist of image encryption histogram analysis, key space analysis, key sensitivity analysis, and correlation analysis.A color histogram is a presentation of the statistical characteristics and distribution of the image pixels and is analyzed in terms of three colors: R, G, and B. As can be seen from the simulation results in 100. Consequently, the security of the image encryption system is improved and the resistance to exhaustive attacks is increased [Cryptographic system security and resistance to exhaustive attacks are affected by the size of the key space. The sequences of the 6D discrete hyperchaotic system (21) are applied at the encryption stage, as the production of keys depends mainly on the parameters and initial conditions of the system. Hence, all the iterative variables of the proposed chaotic system (ncreased ,25.Key sensitivity is an important measure to evaluate the security of an encrypted image. Security is highly reliable if any minimal change to the key results in a large modification; thus, the more sensitive the key, the more secure the encryption system. To evaluate the sensitivity of the key of the proposed scheme, the image was decrypted with a keystream with slight differences, the initial values were set to To prevent data from being attacked or lost, it is necessary to perform cutting attack analysis. The same encrypted Lena as in The analysis of image pixel correlation is one of the important indicators of the encryption effect of encrypted images. The color images were analyzed for correlations from R, G, and B, which are represented as red, green, and blue colors, respectively. In addition, the original image has a strong correlation between adjacent pixels, and an effective encryption system can reduce the image pixel correlation considerably. The correlation coefficient results for the Lena test images and their corresponding encrypted images are shown in To demonstrate the correlation visually, we plotted scatter plots of all sampled pixel pairs. The correlations between the test image Lena and its corresponding R, G, and B color pixels are shown separately. In this paper, two discrete chaotic systems of different dimensions are constructed. Additionally, the dynamics of the new systems are analyzed, and the phase diagram, Lyapunov exponent diagram, and bifurcation diagram of the systems are presented and analyzed simultaneously. The proposed 3D and 6D discrete chaotic systems were constructed as drive systems, and the response systems were constructed by employing the new generalized synchronization method incorporating error-feedback coefficients. The experimental results show that the design of adaptive generalized synchronous systems can be realized provided that the feedback coefficient (


Living donor kidney transplantation (LDKT) is the best treatment option for patients with kidney failure and offers significant medical and economic advantages for both patients and health systems. Despite this, rates of LDKT in Canada have stagnated and vary significantly across Canadian provinces, the reasons for which are not well understood. Our prior work has suggested that system-level factors may be contributing to these differences. Identifying these factors can help inform system-level interventions to increase LDKT.Our objective is to generate a systemic interpretation of LDKT delivery across provincial health systems with variable performance. We aim to identify the attributes and processes that facilitate the delivery of LDKT to patients, and those that create barriers and compare these across systems with variable performance. These objectives are contextualized within our broader goal of increasing rates of LDKT in Canada, particularly in lower-performing provinces.This research takes the form of a qualitative comparative case study analysis of 3 provincial health systems in Canada that have high, moderate, and low rates of LDKT performance . Our approach is underpinned by an understanding of health systems as complex adaptive systems that are multilevel and interconnected, and involve nonlinear interactions between people and organizations, operating within a loosely bounded network. Data collection will comprise semistructured interviews, document reviews, and focus groups. Individual case studies will be conducted and analyzed using inductive thematic analysis. Following this, our comparative analysis will operationalize resource-based theory to compare case study data and generate explanations for our research question.This project was funded from 2020 to 2023. Individual case studies were carried out between November 2020 and August 2022. The comparative case analysis will begin in December 2022 and is expected to conclude in April 2023. Submission of the publication is projected for June 2023.By investigating health systems as complex adaptive systems and making comparisons across provinces, this study will identify how health systems can improve the delivery of LDKT to patients with kidney failure. Our resource-based theory framework will provide a granular analysis of the attributes and processes that facilitate or create barriers to LDKT delivery across multiple organizations and levels of practice. Our findings will have practice and policy implications and help inform transferrable competencies and system-level interventions conducive to increasing LDKT.DERR1-10.2196/44172 End-stage renal disease represents a major public health burden. Patients needing dialysis have extremely poor survival rates when compared with the general population ,2. This Kidney transplantation, in particular living donor kidney transplant (LDKT), is widely regarded as the best therapeutic option for patients with kidney failure. When compared with patients undergoing dialysis, those who have undergone kidney transplantation experience a 64%-75% lower risk of death by the first year following transplantation -13. LDKTDespite its significant benefits, LDKT rates in Canada have stagnated over the past decade and continue to average around 12-14 living donors per 1 million population. This is despite national efforts to increase LDKT, such as the paired kidney exchange program ,22,23. TCurrently, the impetus of finding living donors is largely placed on the patient, and much of the present work to increase LDKT focuses on patients and addressing these microlevel barriers . We condAs such, the objective of the study described in this protocol is to generate a systemic interpretation of LDKT by identifying the attributes and processes that facilitate the delivery of LDKT in a provincial health system and those that create barriers. We also aim to identify the differences between these attributes and processes by comparing higher- and lower-performing systems. These objectives are contextualized within our broader goal of increasing rates of LDKT in Canada, particularly in lower-performing provinces. Our primary research question is the following: what are the attributes and processes of provincial health systems that account for variability in LDKT rates?how and why these differences in performance exist. Qualitative methods have established relevance to answering these questions in health research [This study takes the form of a comparative case study analysis as described by Yin ,29 and iresearch . Understresearch . Our quaresearch . It willConceptually, our approach is underpinned by an understanding of health systems as complex adaptive systems (CASs). The concept of CAS stems from the complexity theory and takes a dynamic systems approach. A CAS is “an entity composed of many different parts that are interconnected in a way that gives the whole capabilities that the parts don’t have on their own” . A proviThere also exists a tight fit between a CAS approach and case study methodology . ResearcIn accordance with the CAS theory, we defined each provincial “case” as the health system involved in facilitating LDKT. Adapted from the 4-level model proposed by leading agencies  we mappeWe will conduct a comparative case study between British Columbia, Ontario, and Quebec, which represent respectively high, moderate, and low performance in LDKT as defined by the percentage of LDKTs to all transplantation performed annually . These tOur study follows sequential stages of data collection and analysis . We haveParticipants from different levels of the health system, as shown in To recruit participants, purposive criterion sampling was used to invite key leadership at organ donation organizations, provincial renal programs, and transplant centers. Participants were considered to have key leadership roles if they held decision-making authority with interorganizational impact. Thereafter, snowball sampling was used to recruit providers from kidney care clinics and dialysis centers ,55. DataSemistructured interviews were conducted to understand the dynamic organization, governance, and care entailed in LDKT delivery and the interdependencies between the elements of each provincial health system. We also sought to understand what aspects of the system variously promoted or hindered patient access to LDKT. Interview guides for professional participants addressed their involvement in facilitating LDKT for patients, their interactions with other professionals in this process, their attitude toward LDKT, and which phenomena helped and which ones posed challenges in their work. Interview guides for donors and recipients of LDKT focused on their experiences of LDKT, their perception of care, and what helped and hindered their care path. Distinct interview guides with open-ended questions were developed for each category of participant with the combined expertise of our research team and preliminary document review  to compare case study data and generate explanations for our research question. The RBT is a strategic management theory that provides a framework for explaining and predicting the basis of an organization’s competitive performance and advantage . RBT invFollowing inductive coding and individual analysis of data collected from British Columbia, Ontario, and Quebec, we will use an RBT framework to analyze and compare our case study data and generate explanations for our research question. To do this, we will organize codebooks from each province into capabilities identified from the RBT literature, following questions stemming from these capabilities to guide our organization . AccordiEthics approval for this study was obtained from the McGill University Health Centre Research Ethics Committee (MP-37-2021-7126/LDKT Case Study). This study is being conducted in accordance with the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (2014), and the Declaration of Istanbul.This project was funded by a grant from a Gift of Life Institute, a Clinical Faculty Development Research Grant from the American Society of Transplantation from 2020 to 2021, and by a Health Research Grant from the Kidney Foundation of Canada. Individual case studies of British Columbia, Ontario, and Quebec were carried out between November 2020 and August 2022. The individual case study findings of LDKT delivery in British Columbia have been published ,73. FocuThis study aims to produce a system-level understanding of LDKT delivery in Canada’s 3 most populous provinces that have variable rates of LDKT, presenting a unique opportunity for comparative analysis. Informed by quantitative data , we are To our knowledge, a comparative case analysis approach has not been used in the field of nephrology or kidney transplantation. Our approach has implications in these disciplines where there exists a poor understanding of system-level factors leading to inferior outcomes, inequities in access to therapy, and fractured transitions of care. This work also has global implications as LDKT is the main way to obtain a transplant in many countries that lack infrastructure for deceased donation. Based on our preliminary results and background work, we believe that to make significant improvements to LDKT delivery, interventions must target the dynamic relationships between different elements of a system. Much of the current work has focused on microlevel interventions to improve LDKT delivery ,51, missThe following limitations to our study may apply. First, our data collection largely pertains to 3 provinces of Canada and our findings may not be applicable to other regions and countries. Nonetheless, it should be noted that Quebec, Ontario, and British Columbia are Canada’s most populous provinces and represent 75% of the Canadian population, and our focus group data also go some way to establish the pertinence of our findings to other provinces. Our data also lay the foundations to extend our work across Canada and to other countries. Second, our research will not comprehensively explore the system-level factors leading to disparities in LDKT, such as gender and sex disparities and low rates of LDKT in Indigenous and other vulnerable populations. However, the data collected in this study will inform future systematic approaches needed to address this complex issue.Another limitation may pertain to the challenge of delineating the “boundaries” of the health systems that form the basis for our cases. Identifying the unit of analysis for case study research has long been identified as a challenge , and in LDKT is the optimal treatment option for patients with kidney failure; yet, rates of LDKT have stagnated in Canada and vary significantly across provinces. There is a need to better understand how health systems deliver LDKT to patients. Following our prior work that has suggested system-level differences contributing to variability in LDKT performance, we will generate a systemic interpretation of LDKT delivery by identifying the attributes and processes that facilitate or create barriers to the delivery of LDKT. We will also identify the differences between these attributes and processes by comparing higher- and lower-performing provincial health systems. This qualitative comparative case study analysis is informed by CASs, and data analysis will be carried out in accordance with the RBT. Our findings will have practice and policy implications and help inform specific strategies, regulations, and infrastructure that are transferrable competencies and conducive to promoting the service delivery of LDKT.


Furthermore, the addition of ozone increased the volatile content of soot particles and improved soot oxidation reactivity.Ozone is a prospective additive for enhancing and controlling combustion under lean or very lean conditions, and reduces NOx and particulate matter emissions simultaneously. Typically, in studying the effects of ozone on combustion pollutants, the focus is on the final yield of pollutants, while its detailed effects on the soot formation process remain unknown. Here, the formation and evolution profiles of soot containing morphology and nanostructures in ethylene inverse diffusion flames with different ozone concentration additions were experimentally studied. The surface chemistry and oxidation reactivity of soot particles were also compared. The soot samples were collected by a combination of the thermophoretic sampling method and deposition sampling method. High-resolution transmission electron microscopy analysis, X-ray photoelectron spectroscopy and thermogravimetric analysis were applied to obtain the soot characteristics. The results showed that soot particles experienced inception, surface growth, and agglomeration in the ethylene inverse diffusion flame within a flame axial direction. The soot formation and agglomeration were slightly advanced since the ozone decomposition contributed to promoting the production of free radicals and active substances in the ozone added flames. The diameter of primary particles in the flame with ozone addition was larger. With the increase of ozone concentration, the content of soot surface oxygen increased and the ratio of sp As anottability ,12.2 at the beginning of combustion. Halter et al. [3 ozone concentration in air. Ombrello et al. [3H8 flame by experimental and numerical methods. The experimental result showed that the flame propagation speed was enhanced by 8% when the ozone concentration in the oxidizer stream was 1260 ppm. The enhancement in combustion and flame propagation speed could be attributed to the ozone decomposition in the preheating stage. Wang et al. [2/CO, n-heptane, iso-octane and other fuels [2/CO flames with different dilution gases. They also found that with ozone addition, the flammability limit expanded and the laminar flame velocity increased, and the enhancement effect on the flame velocity was more significant under near-limit conditions.Nishida and Tachibana  studied r et al.  studied o et al.  investigg et al.  investiger fuels ,19,20. Ver fuels  carried er fuels  numericax and SO2 by injecting ozone, and the result showed that the removal efficiency of NOx and SO2 was about 95% and 100%, respectively. Wang et al. [x, SO2, and Hg by ozone injection in a quartz flow reactor, and they found that the removal efficiency of NO and Hg gradually improved with increasing ozone concentration. A similar result was found by Sun et al. [x and SO2 using ozone, that NOx removal efficiency enhanced with increased ozone addition. Holder et al. [The effects of ozone on combustion pollutants have also been studied. Tachibana et al.  investigg et al.  further n et al.  when simr et al.  investigr et al.  used an r et al.  comparedPrevious studies have investigated the effects of ozone on flame ignition delay time, laminar flame velocity, flame stability, and combustion pollutants both experimentally and numerically. The addition of ozone improves combustion and laminar flame speed, shortens ignition delay time, expands flame flammability limit, and enhances combustion efficiency. The oxidizing reactions and chemical properties are affected by the ozone atmosphere during the course of soot oxidation. Therefore, it could be speculated that ozone addition in flame influences the generation of soot in combustion. However, these studies have not explored the particles produced with ozone during the combustion process, and the effects of ozone on soot properties in flame remain unknown.Thus, the present study aims to obtain the evolution profiles of soot in ethylene inverse diffusion flames in ozone atmosphere, including physical and chemical characteristics. The soot particles are collected by local and global sampling methods as in our previous studies ,32. The 2H4 is supplied by the intermediate tube, and the shield gas N2 is provided in the outer tube. To generate an O3 atmosphere, an ozone generator is connected to the O2 gas pipeline, and then part of the O2 is converted into O3. The partially O3 and O2 mixture gases are supplied to the central tube of the IDF as the oxidizer. The O3 concentration is measured online by an ozone detector, which is connected to the outlet of the mixing device of oxidizer gas from the ozone generator and diluent gas N2. The detailed experimental system is shown in An inverse diffusion flame (IDF) burner, the same as in the previous works ,32,33,342 gas in the flames is fixed. The concentration of ozone is changed by adjusting the discharge power of the ozone generator. According to previous studies on ozone’s effects on combustion characteristics with different concentrations [During the experiments, the flow rate of Otrations ,18,20,21The flame temperatures were measured by the rapid insertion method with a B-type thermocouple ,33. To e3 is added or not, the flame is very bright. The naked eye cannot directly observe the flame variation when the ozone concentration changes.The flame images with different ozone concentrations are shown in The flame temperature distribution at different heights of the flame center line and boundary line (including the thermophoretic sampling locations) is presented in In the upper part of the flame, the soot particles present long chains or large clusters, and the aggregates are more branched. While in the lower part of the flame, the soot particles are mainly composed of individual particles, and aggregates are governed by a smaller number of primary particles. The TEM image of the soot gathered from the lowest sampling position (HAB = 4 mm) . Previous studies ,42,43,44The HRTEM images in When the sampling height increases from HAB = 30 mm to 40 mm, the soot particles are mainly composed of long or large clusters with more branches, as shown in The nanostructure characteristics of soot at different HAB in O5 flame are shown in 3 + (M) = O + O2 + (M) and releases O atoms [2H2-addition (HACA) is important in soot formation [2H4, and C2H4, then converts to important intermediates through two possible pathways: (1) C2H4 + O = CH3 + HCO, and (2) C2H4 + H(+M) = C2H5 (+M) [2H4 lead to subsequent reactions relating to soot inception. Thus, the soot formation process is promoted in the flame with a higher ozone concentration. The diameter of the particles increases due to the surface growth from HAB = 4 mm to 10 mm.With lower magnification at HAB = 4 mm, the visible particulates are rare, as the particles are just beginning to form. In this flame region, liquid-like materials (indicated by dotted arrows) with irregular shapes and high transparency coexist with solidified soot particles. The presence of these irregular-shaped features shows the soot inception course. At HAB = 10 mm, there are still singlet particles, while a small number of aggregates also appear, composed of several primary particles. The small aggregates appear earlier than that in O0 and O5 flames, illustrating a promotion in soot particle growth with higher ozone concentration. The effect of ozone addition on the facilitation of soot formation can be understood by considering the role of ozone decomposition. Ozone decomposes through the reaction O O atoms ,47. It iormation ,49,50. T2H5 (+M) . The conWhen the sampling height was increased from HAB = 10 mm to 20 mm, more chains of clustered soot aggregates appeared. In this region, the dominant process is soot particle growth and agglomeration. In the middle regions of the flame, the primary particle size increases because of surface growth and PAH condensation, and the agglomerates grow due to a cluster–cluster aggregation (CCA) by collisional growth , which sThe nanostructure images of soot at different formation stages in O10 shown in The primary particle diameter increases gradually due to surface growth and PAH condensation as the particles move from the bottom to the tip of the flame. A quantitative analysis of the primary particle diameter in the flames with different ozone concentrations is shown in With the increase of sampling height, the diameter of particles increases due to surface growth. From HAB = 4 mm to HAB = 20 mm, the particle diameter increases rapidly due to the dominant surface growth and agglomeration processes. The particle size growth trend slows down from HAB = 20 mm to HAB = 40 mm because in this region, the growth of particle surface gradually ceases, while the agglomeration and carbonization of soot predominate. The particles tend to be more mature, as the nanostructure characteristics show. At HAB = 40 mm, the average peak particle diameter of soot in O0, O5, and O10 flames are 15.8 nm, 16.1 nm, and 16.3 nm, respectively. The average particle size increases when the ozone concentration in the flame increases, and the surface growth of soot is stronger in ozone flames. The variation trend of the primary particle diameter in ethylene inverse diffusion flames is constant with the previous work  regardle2 and sp3 carbon hybridization in the flames with different ozone concentrations are obtained by XPS quantitative analysis, as shown in The surface oxygen content of soot particles and the relative components of sp2/sp3 obtained (data in the upper part of 2 content can indicate graphitic carbon, and the sp3 represents the content of the defect site and organic carbon [2/sp3 can characterize the disorder degree of soot, and the smaller the ratio is, the more disordered the soot particles are. The ratio of sp2/sp3 of soot in O0, O5, and O10 flames is 4.97, 4.03, and 3.85, respectively. With the increase in ozone concentration, the ratio of sp2/sp3 decreases, which demonstrates that sp3 hybrid carbon content is higher in higher ozone concentration flames, indicating a lower degree of graphitization. This is because with higher ozone concentration in the flame, O3 decomposes to O2 and O radical, subsequently increasing the O-atom content in the flame and leading to an increase in the sp3 hybrid component. The soot nanostructure and disorder degree can affect soot oxidation reactivity [The XPS spectra of soot particles in flames with different ozone concentrations are fitted by peaking ,54, and c carbon . Previouc carbon . The actactivity .The average time from the initial oxidation of soot to 90% consumption is about 99.2, 89.8, and 84.9 min, respectively. According to the results of XPS analysis, the degree of graphitization decreases when ozone is added to the flame, which enhances the soot oxidation reactivity and makes it more easily oxidized. In addition, the content of volatile materials in the soot from the flame increases gradually with the increasing ozone content, corresponding to 11.5%, 13.2%, and 14.1% in O0, O5, and O10 flame, respectively. The higher volatile content on the soot surface with a higher ozone concentration leads to higher oxidation reactivity. The possible reason is that the decrease in volatile compounds increases the pore area on the particle surface, which facilitates contact with oxidants ,59.2/sp3 decreased. The soot generated from the flame with higher ozone concentration had higher disordered organization and a lower degree of graphitization, resulting in a higher oxidation reactivity.The soot formation and evolution profiles containing morphology and nanostructure, soot surface chemistry, and soot reactivity were studied in ethylene inverse diffusion flames with different ozone concentrations through a combination of the thermophoretic sampling method and quartz plate sampling method. Soot particles experienced inception, surface growth, agglomeration, and carbonization processes, moving from the bottom to the flame top in the ethylene inverse diffusion flames with or without ozone addition. The soot mass slightly increased under the ozone atmosphere. The soot formation and agglomeration were slightly advanced because the free radicals and active substances were promoted due to ozone decomposition. The diameter of primary particles was larger, and the degree of agglomeration of soot was higher in the ozone flames at the same sampling height. With the increase in ozone concentration in the flames, the soot surface oxygen content increased and the ratio of sp