This is 1.65–3.30 times higher than the Cr film, and is significantly higher than the values of other CSNPs–PDMS transmitters reported elsewhere (22–81 mJ·cm−2). Moreover, we characterized the strain-dependent photoacoustic output of a stretchable nanocomposite film, obtained by delaminating it from the glass substrate. The transmitter could be elongated elastically up to a longitudinal strain of 0.59. Under this condition, it maintained a center frequency of 6.72–9.44 MHz, and 6-dB bandwidth ranges from 12.05 to 14.02 MHz. We believe that the stretchable CSNPs–PDMS composites would be useful in developing patch-type ultrasound devices conformally adhered on skin for diagnostic and therapeutic applications. Considerable attention has been devoted to the development of nanomaterial-based photoacoustic transmitters for ultrasound therapy and diagnosis applications. Here, we fabricate and characterize candle-soot nanoparticles (CSNPs) and polydimethylsiloxane (PDMS) composite-based photoacoustic transmitters, based on a solution process, not just to achieve high-frequency and high-amplitude pressure outputs, but also to develop physically stretchable ultrasound transmitters. Owing to its non-porous and non-agglomerative characteristics, the composite exhibits unique photo-thermal and mechanical properties. The output pressure amplitudes from CSNPs–PDMS composites were 20–26 dB stronger than those of Cr film, used as a reference. The proposed transmitters also offered a center frequency of 2.44–13.34 MHz and 6-dB bandwidths of 5.80–13.62 MHz. Importantly, we characterize the mechanical robustness of CSNPs–PDMS quantitatively, by measuring laser-damage thresholds, to evaluate the upper limit of laser energy that can be ultimately used as an input, i.e., proportional to the maximum-available pressure output. The transmitters could endure an input laser fluence of 54.3–108.6 mJ·cm Photoacoustic transmitters for generating high-amplitude pulsed ultrasound have been developed in either planar or focal configuration, the latter of which allows laser-generated focused ultrasound (LGFU), which is widely used for such applications as histotripsy, drug delivery, sonothrombolysis, and lithotripsy. As effective alternatives to their conventional piezoelectric counterparts, photoacoustic transmitters have been used, taking advantage of their high pressure amplitude, in the order of MPa, and their high frequency spectrum together with broad bandwidth. Their frequency spectrum ranges over tens of MHz (even up to hundreds of MHz), which is determined by an input laser pulse profile  and light-absorber distribution within a transmitter. The input laser pulses can be converted into short ultrasonic pulses, as the output from the photoacoustic transmitters , comprising light-induced heating elements (conducting fillers) and a thermal expansion medium  ,4,5,6,7.−3 K−1) [As transmitter materials, a variety of nanostructures, including graphite, metallic films , gold na−3 K−1) . The pho−3 K−1) ,13,14, e−3 K−1) , using fRecently, stretchable devices have attracted great attention as favorable alternatives to conventional rigid devices, especially for next-generation healthcare and biomedical applications. These devices are capable of accommodating mechanical deformation during their operation, which makes them suitable for personalized healthcare systems, wearable displays and implantable devices ,24,25,26Among the carbon-based nanostructures, candle-soot nanoparticles (CSNPs), which are abundant carbonaceous substances, have gained significant attention due to the advantages of simple production, stability and cost effectiveness ,38,39,40−2. This greatly limits their use to low-fluence applications only [Despite the advantages of CSNPs–PDMS composite transmitters, they have a few disadvantages that need to be addressed. Firstly, during CSNPs deposition, the substrate should endure a high-temperature candle flame ~800–00 °C forons only ,48,49,50−2), the transmitters exhibited a 1.65- to 3.30-fold higher laser damage threshold (54.3−108.6 mJ·cm−2). Such values are significantly higher than the values previously reported using similar CSNPs–PDMS composites –PDMS (elastomer) nanocomposite-based photoacoustic transmitters, which can generate strong pressure amplitudes and endure a high laser fluence input. We describe the fabrication process of the transmitters, followed by the characterization of their photoacoustic outputs. The results confirm that the CSNPs–PDMS composite transmitters fabricated on a planar glass substrate generates peak pressure amplitudes 20, 22, 23 and 26 dB higher than that of a reference Cr film. These transmitters offer center frequencies of 2.44–13.34 MHz, and 6-dB bandwidths of 5.80–13.62 MHz. Furthermore, we obtained a stretchable nanocomposite transmitter by delaminating a composite film from the glass substrate, and evaluated its performance. As the composite is made of elastomeric polymer (PDMS), the transmitter is readily stretchable. This stretchable nanocomposite exhibited a center frequency of 6.72–9.44 MHz and a 6-dB bandwidth range of 12.05–14.02 MHz, when stretched by 19 mm. Finally, we quantified the mechanical robustness by measuring the laser-induced damage threshold, which determines the maximum-absorption energy fluence that can be tolerated in producing the ultimate output pressure from our proposed transmitters with optical absorption of ~100%. As compared to the Cr reference film (measured damage threshold = 32.9 mJ·cmcm−2 [−2 ). A homogeneous dispersion method was utilized to prepare a solution of CSNPs uniformly blended in PDMS. A nanocomposite film was fabricated using a drop-casting process. The schematic diagram for fabrication is shown in We confirmed the cross-sectional views of the fabricated CSNPs–PDMS composites by employing scanning electron microscopy (SEM) . The CSNPs are spherical in shape (diameter around 40–50 nm) with a three-dimensional porous structure . Figure Q-switched pulsed Nd:YAG laser  . The input laser energy to the transmitters was attenuated by utilizing neutral density filters. Laser irradiation was supplied to the transparent (planar) side of the transmitter. The photoacoustic waves generated by the transmitters were detected by using a polyvinylidene difluoride (PVDF) needle hydrophone with a 1-mm diameter . The hydrophone was placed 2 mm away from the transmitters to satisfy a plane wave incidence configuration. The detected hydrophone signal was recorded by the digital oscilloscope  without any amplification. The waveforms generated by the transmitters were obtained by averaging 20 signal traces in a time-domain.The proposed transmitters were characterized by utilizing the experimental setup depicted in P) from thin-film photoacoustic transmitters increases with incident optical fluence (F), Grüneisen coefficient (Γ) and optical absorption (A). It can be represented as the following: c, Fth) determines an upper limit of such incident optical fluence. A higher optical input (F ≥ Fth) causes physical damage to the transmitter. Hence, for a given optical absorption, the higher the damage threshold is, the stronger will be the maximum-available output pressure achieved by the transmitters.The output pressure  until a physical damage occurred.The mechanical robustness of each transmitter was assessed by measuring the laser-induced damage threshold. We measured time-domain waveforms generated by the CSNPs–PDMS composites  and the reference Cr film using the same laser energy of 1.5 mJ/pulse. The measured output pressure waveforms are shown in The measured waveforms resulted from the summation of forward-going (the transmitter to the detector) and backward-going (toward the glass substrate) waves, the latter of which is reflected by the glass substrate, changing its direction to forward. The depth of the optical absorption in the transmitter determines the delay in time between these propagating waves. The greater the absorption thickness is, the longer the time delay will be between them, which causes the output pulse width to broaden . NormaliFor the stretchable nanocomposite (p40d), we measured the time-domain waveforms for different stretching lengths. The original length of the nanocomposite without being stretched was found to be 32 mm, which was then stretched in 1-mm steps to the maximum of 19 mm before being damaged. The maximum-achievable longitudinal strain was 0.59 for the 19-mm elongation from the initial 32-mm length.S) values  are represented in S = 0 corresponds to the case without any strain applied to the nanocomposite. After the elongation process, the nanocomposite film completely recovered its initial length. As the nanocomposite thickness was reduced by the stretching process, the pressure amplitude was enhanced. A 3.45-dB higher peak pressure amplitude was obtained at S = 0.46 (the condition before damage), as compared to that obtained at S = 0.15. However, the pressure at S = 0.15 was still 2.48-dB higher than that of the unstretched composite. The frequency spectra obtained from the time-domain waveforms are represented in The normalized output pressure waveforms for different strain  [We obtained the stress-strain relation for the stretchable nanocomposite. In this case, the same sample (p40d) was utilized, with an original length of 12 mm and width of 25 mm. The composite was again stretched in 1-mm steps. Then, the corresponding force and stress were measured. For a longitudinal strain of 0.58 , the total applied force and stress were measured to be 0.74 N and 2.47 kPa, respectively.  = 0.59) .n (dB)” was increased by a step of 1-dB. At n = 0, the obtained average laser beam power, pulse energy (E) and fluence (F) were 16.67 mW, 1.60 mJ and 22.9 mJ·cm−2, respectively. As shown in n = 2 dB, corresponding to E = 2.30 mJ and F = 32.9 mJ·cm−2, whereas the ablation process for p10 started to appear when E was equal to 3.80 mJ . The laser damage threshold (Fth) of p10 was 1.65-fold higher than that of the reference Cr film. For p20, the ablation started at E = 4.60 mJ, corresponding to Fth = 65.7 mJ·cm−2. The ablation threshold fluence for the p30 increased to 91.4 mJ·cm−2, which was 39% more than that of p20. Similarly, p40 presents a ~19 % higher damage threshold than p30, corresponding to Fth = 108.6 mJ·cm−2. For p10−p40 with ~100 % absorption, the maximum-absorption energy fluences  obtained were 54.3, 65.7, 91.4 and 108.6 mJ·cm−2, respectively. This confirms that the damage threshold increases with the ratio of the PDMS to CSNPs.We measured the laser-induced damage threshold for our transmitters. Microscopic images for the transmitters are depicted in −2. This is similar to other values reported elsewhere for CSNPs–PDMS composite films  [−2 obtained from the CNT–PDMS composite films containing CNTs grown via a chemical vapor deposition process [The p10 transmitter includes a higher concentration of CSNPs in PDMS than the others, leading to a shallower depth of optical absorption . Thus, under the same irradiation condition, the physical adhesion between the composite and the glass substrate for p10 would be exposed to a thermal load heavier than the other lower-density transmitters. For this reason, the p10 transmitter has the lowest damage threshold among transmitters compared here. Previously, the output pressure amplitude of p10 was two-fold stronger than that of p40 a. This m mJ·cm−2 ) and CNTm−2 [−2) . However process .Although the CSNPs–PDMS composite has an advantage in terms of its simple and low-cost fabrication process, its damage threshold still limits its possible application to diagnosis, not therapy. Due to the limited output pressure amplitude, previous CSNPs–PDMS composites were not used for in vivo applications requiring a significant tissue depth, of at least >1~2 cm. For cavitation-based therapy, photoacoustic lenses with low damage threshold values were often operated in a dual excitation manner with an additional transducer, or with externally injected seed bubbles . In orde-2, which is 36% higher than the previous CSNPs–PDMS transmitters [We characterized the performances of the CSNPs–PDMS-based photoacoustic transmitters. We prepared the solution of CSNPs–PDMS, and analyzed the output pressure waveforms. The CSNPs–PDMS transmitters exhibited a center frequency of 2.44–13.34 MHz, and 6-dB bandwidth ranges from 5.80 to 13.62 MHz. As the ratio of PDMS to CSNPs increases, the amplitude of the acoustic signal decreases . Importantly, we quantified the mechanical robustness with different ratios of PDMS to CSNPs, and then compared them with the reference Cr film. The CSNPs–PDMS transmitters not only produced significantly high-amplitude pressure outputs, but also endured a laser fluence up to 108.6 mJ cmsmitters . Moreove


The major purpose of this research was to study the predictive value of the top managers’ psychological characteristics regarding their networking behavior. In the international business management context of small- and medium-sized enterprises, we took the top managers’ cultural intelligence and emotional intelligence as determinant capabilities to perform better in their external networking. The sample was composed of 307 Portuguese SMEs’ international decision-makers, specifically founders, owners, chief executive officers (CEOs), managers of international activities, international market managers, or commercial managers. The data was collected from 2–30 April 2019 through online surveys directed to the Portuguese decision-makers that were directly responsible for the firms’ international activities. As a data collection instrument, the surveys were pretested and sent by e-mail. The average age of the participants was approximately 50 years old for males and 45 years old for females. We used self-reported measures to assess the different constructs and the hierarchical regression analysis to test our hypotheses. The results showed that cultural intelligence and emotional intelligence were significant drivers of decision-makers’ external networking behavior. A new factor structure concerning external networking behavior was retained. The major results exhibited the predictive value of some cultural and emotional intelligence dimensions over the new retained external networking behavior factors. Therefore, in the international business management context, the capability to adapt to new cultural contexts, as well as the capability to reason about emotions, improved the international decision-makers’ external networking behavior. The present research was grounded in the international business management, networks, and psychology fields. In the international management context, this study focused on the networking behavior and psychological characteristics of the international decision-makers of the international small- and medium-sized enterprises (SMEs). The conceptual and empirical approach took decision-makers’ psychological characteristics as important antecedents of their networking behavior in the setting of SMEs’ internationalization.This research connected the international top managers’ cultural and emotional intelligences to their external networking behaviors, suggesting that the capability to adapt to new cultural contexts, as well as the capability to reason about emotions and to use emotional knowledge to enhance thought, improved their networking behaviors, specifically, in building and maintaining external contacts, in using external contacts in a win–win perspective, and in their commitment to the creation of external contacts. To our knowledge, the investigation concerning the effects of emotional intelligence (EI) and cultural intelligence (CQ) on external networking behaviors is under-researched. According to our research, little is known about the relationship between these two intelligences and external networking behavior. We, therefore, proposed a model, where the main research question was whether the levels of CQ and EI of the international SMEs’ decision-makers were associated with their engagement intensity in their external networking behavior (ENB). This embodies an important line of research due to the importance of networks in the international business management context and due to the relevance of the individuals’ emotional and cultural intelligences to their behaviors.The present research was grounded in the network approach of SMEs’ internationalization, where Chetty and Holm  argued tInternationalization is an important decision taken by SMEs to promote their growth and competitiveness . SMEs arTop managers’ CQ is an important characteristic for those who interact in multicultural settings. Those with higher levels of this intelligence are better prepared for interactions in intercultural environments  and for In the context of international business management, like other investigations, our research reinforced the importance and the central role of the top managers’ psychological characteristics ,27, as wAs emphasized above, we took CQ and EI as drivers of the international decision-makers’ external networking behavior. CQ contributes to SMEs’ international network ties, helping to build quality relationships with foreign customers, suppliers, and competitors . Its rolConcerning the structure of this research, The relevance of personal relationships is present in business internationalization, a fact that gives emphasis to the networks as an important subject of research in this context ,14,30,33ENB concerns individuals’ behavior with contacts from other organizations, i.e., behaviors about developing relationships outside the firm . ENB is In the international business management context, to pursue foreign activities and their inherent challenges, managers need some important skills . This reIn the present research, we focused on the EI of the international SMEs’ decision-makers. It is important to study EI in the organizational context ,37. HoweWithin organizations, given that interactions between individuals are a reality, emotions thrive and emotionally intelligent individuals will be better prepared to perform their responsibilities . “EmotioThis is an important ability that allows for an effective adjustment of those who operate in multicultural settings . It imprMeeting people outside the organization takes more effort than internal networking . The estConsequently, taking the above into consideration, the present research took EI as a predictor of ENB and its dimensions. Those that possess higher levels in this intelligence perform better than others in terms of external networking behavior. In summary, EI should help to capitalize on decision-makers’ actions toward ENB. Therefore, we formulate Hypothesis 1 (H1) as the following:Hypothesis 1 (H1).The higher the level of a decision-maker’s EI, the better their performance regarding their ENB.For those who interact in the international business management context, CQ is a significant capability . It is aIn relation to networking, its core characteristic is concerned with behaviors toward interpersonal relationships  by buildAs referred, the present research focused on international SMEs’ top managers’ ENB and on their CQ as a significant antecedent. CQ emerges as a fundamental competence within the increasing cultural interactions in business reality, with its cultural differences, challenges, and complexities . Taking Hypothesis 2 (H2).The higher the level of a decision-maker’s CQ, the better their performance regarding their ENB.Earley and Mosakowski  stated tHypothesis 3 (H3).In the international context, a decision-maker’s CQ is a more significant predictor of ENB than their EI.Taking into consideration the multidimensional nature of the constructs, we intended to go deeper regarding our analysis concerning the relationship between the dimensions of EI and CQ with the dimensions of the top managers’ international ENB. We took the external networking behaviors to include the following three dimensions: building and maintaining external contacts (BMEC), using external contacts in a win–win perspective (UECWW), and commitment to creating external contacts (CCEC). The EI was composed of self-emotions appraisal (SEA), others-emotions appraisal (OEA), use of emotion (UOE), and regulation of emotion (ROE). Therefore, we suggest that those who better assess and learn about their own emotions (SEA), thereby promoting better social interactions , are betIn this sense, we formulated hypotheses four (H4) to nine (H9) as the following:Hypothesis 4 (H4).The higher the level of a decision-maker’s EI dimensions , the better the performance of their ENB regarding building and maintaining external contacts (BMEC).Hypothesis 5 (H5).The higher the level of a decision-maker’s EI dimensions , the better the performance of their ENB regarding using external contacts in a win–win perspective (UECWW).Hypothesis 6 (H6).The higher the level of a decision-maker’s EI dimensions , the better the performance of their ENB commitment to creating external contacts (CCEC).Hypothesis 7 (H7).The higher the level of a decision-maker’s CQ dimensions , the better the performance of their ENB regarding building and maintaining external contacts (BMEC).Hypothesis 8 (H8).The higher the level of a decision-maker’s CQ dimensions , the better the performance of their ENB regarding using external contacts in a win–win perspective (UECWW).Hypothesis 9 (H9).The higher the level of a decision-maker’s CQ dimensions , the better the performance of their ENB commitment to creating external contacts (CCEC).According to the formulated hypotheses (H1 to H9), we present the following This research focused on decision-makers’ external networking behaviors in the international business field. Therefore, to study their external networking behaviors in international business environments, data was collected from the decision-makers directly responsible for international activities in Portuguese international SMEs. The sample was composed of founders, owners, chief executive officers (CEOs), managers of international activities, international market managers, or commercial managers. As a criterion for inclusion in the study, we requested the position of each respondent and followed the European Union’s definition of SMEs . In the The average age of participants was approximately 50 and 45 years old, for males and females, respectively, and the average of the respondents’ international experience was living in 1.2 countries.The survey, as a data collection instrument, was pretested by a panel of 10 individuals representing managers in internationalized enterprises. Minor changes were made in a few items. The data was collected from 2–30 April 2019, exclusively through online surveys sent by e-mail. In the survey development, we used previously validated scales with minor adaptations. All scales were in the English language but the sample was made up of native Portuguese speakers. To carry out this research in the Portuguese context, in relation to EI, we used the Portuguese translation of the Wong and Law Emotional Intelligence Scale (WLEIS) by Rodrigues et al. . In the In business management research, the use of self-reporting measures is prone to bias, where the appearance of the social desirability effect in the responses is a reality that must be controlled . Given tSMEs have high economic and social relevance and are considered the engine of the entire European economy . StudyinIt should be noted that according to the observatory of economic complexity, in 2018, Portugal was the 44th largest export economy in the world . TherefoAccording to the European Commission , the PorDiagnostica in 2006, Wolff and Moser developed a 44-item German measure of networking. This scale distinguishes between internal and external networking behaviors, with twenty-two items each [Networking is a complex construct with operationalization and measurement difficulties . The preems each . In eachems each . Concernems each ,40. Giveems each  to assesIn the present research, the scale of EI was a self-reported psychometric measure under the theoretical framework of EI as an ability , followiTo measure CQ, we used Ang et al.’s  self-repThese three constructs  were measured on a five-point Likert scale response format with 1—strongly disagree, 2—disagree, 3—neither agree nor disagree, 4—agree, and 5—strongly agree.Social Desirability (SD)With the use of self-reported measures, it is crucial to measure the socially desirable response tendency, whether in the context of personality, affection, attitudes, and other individual characteristics . To thisAgeThe age of the managers is seen as a proxy for their cognitive abilities and knowledge . In the Gender (G)Gender may influence the intelligences in the present research; thus, we used it as a control variable, as in other studies in this area ,38,48. IRespondents’ International Experience (RIE)The international experience of managers influences their knowledge, and despite the existence of more accurate measures of international experience , we askePositionTo participate in this research, the respondents had to hold one of the following positions and indicate which one: founder, owner, CEO, manager of international activities, international market manager, or commercial manager.This research took some steps to control and avoid the common method bias (CMB). It should be noted that the same individual provided all the collected data for each firm . FollowiThe collected data were processed using the IBM SPSS Statistics of the Statistical Package for Social Science program version 25, Armonk, New York, United States of America.We performed an exploratory factor analysis on all the constructs in the study. All dependent, independent, and control variables were tested using the principal components extraction method with a varimax rotation.Concerning the adapted ENB nine-item scale, according to the exploratory factor analysis, we retained three factors, taking into consideration that there was a total explained variance of 60.69%. That was the criterion that we used for factor extraction. In the field of the social sciences, a factor structure that accounts for an explained variance of 60% (or even less) is considered satisfactory . After tTo verify the adequacy of the collected information for factor analysis, we used the Kaiser–Meyer–Olkin (KMO) measure and Bartlett’s sphericity test. According to the observed values for all constructs , pursuinWe performed a correlation and descriptive analysis to get a first glimpse of the relationships between the variables. The results are reported in The key variables of the research were significantly correlated . Age and gender did not reveal any significant correlations with EI, CQ, or ENB. Regarding SD, significant correlations were observable with EI and CQ. SD effects were controlled in the hypothesis testing. Finally, RIE exhibited significant correlations with CQ and SD.Subsequently, to carry out the hypothesis testing, several hierarchical linear regression analyses with a confidence interval of 95% were performed, controlling for age, gender, RIE, and SD. Regarding the sample size adequacy, we observed the rule of five observations, as well as the preferable level of fifteen or even twenty observations for each independent variable .Hypothesis 1, Hypothesis 2, and Hypothesis 3p < 0.001.According to the statistical F-test, the final regression models were significant at Hypothesis 1 stated that the higher the level of a decision-maker’s EI, the better their performance regarding their ENB. EI emerged as a significant positive predictor, accounting for 9.7% of the variation in ENB  = 2.452, p = 0.000) and EI  = 2.809 p = 0.005).Hypothesis 3 stated that a decision-maker’s CQ is a more significant predictor of their ENB than the decision-maker’s EI. This hypothesis was supported by the results : CQ (β =d) = 2.185, d = 2.156, and d = 2.163 for final model of H1, final model of H2, and final model of H3, respectively. The linearity and homoscedasticity assumptions and the normality of the residuals were confirmed [In these regressions, regarding casewise diagnostics, none of the cases that deserved some attention exhibited a Cook’s distance greater than one or a centered leverage value greater than three times the calculated average value, and none were above an absolute value of one in terms of DFBeta statistics . No inflonfirmed .Hypothesis 4, Hypothesis 5, and Hypothesis 6The following regression results  report tAccording to the results of Hypothesis 4, others-emotions appraisal (OEA), use of emotion (UOE), and regulation of emotion (ROE) significantly predicted the decision-makers’ engagement in building and maintaining external contacts (BMEC). A positive relationship was observable, as expected, between those EI dimensions and BMEC. Thus, as OEA, UOE, and ROE increased, so did BMEC. SEA was not statistically significant. Therefore, this hypothesis was partially supported, since SEA was not significant.Hypothesis 5 stated that the higher the level of the EI dimensions of a decision-maker, the better their performance regarding ENB when using external contacts in a win–win perspective (UECWW). As expected, the use of emotion (UOE) exhibited a significant and positive effect on UECWW . HoweverHypothesis 6 stated that the higher the level of the EI dimensions of a decision-maker, the better their performance regarding ENB in the commitment to creating external contacts (CCEC). As expected, the use of emotion (UOE) and the regulation of emotion (ROE) exhibited a significant and positive effect on CCEC . SEA andRegarding casewise diagnostics, no influential cases were detected with an undue influence on the regressions. All the models’ assumptions were verified.Hypothesis 7, Hypothesis 8, and Hypothesis 9The following regression results  report tHypothesis 7 stated that the higher the level of a decision-maker’s CQ dimensions, the better their performance regarding ENB when building and maintaining external contacts (BMEC). Metacognitive (MC), cognitive (COG), and motivational (MOT) dimensions of CQ, as expected, had a significant and positive effect on BMEC . The behHypothesis 8 stated that the higher the level of a decision-maker’s CQ dimensions, the better their performance regarding ENB when using external contacts in a win–win perspective (UECWW). Motivational (MOT) and behavioral (BEH) dimensions had a significant and positive effect on using external contacts in a win–win perspective . TherefoHypothesis 9 stated that the higher the level of a decision-maker’s CQ dimensions, the better their performance regarding ENB in the commitment to creating external contacts (CCEC). The cognitive (COG) dimension was the main predictor, with a significant and positive effect on CCEC . This hyRegarding casewise diagnostics, no influential cases were detected with an undue influence in the regressions. SD did not present any concerns across the models. All the models’ assumptions were verified.In order to summarize the hypotheses testing, In this research, we tested international decision-makers’ psychological characteristics as the main predictors of their networking behaviors. We took cultural intelligence and emotional intelligence as significant characteristics that boost international decision-makers’ external networking behavior in the SMEs’ internationalization contexts. According to the results, this investigation showed the pivotal role of CQ and EI in external networking behavior. As expected, EI had a positive influence on ENB, indicating that the higher the capability of the decision-makers to reason about emotions and to use emotional knowledge to enhance thought , the betThe present research also studied the value of the different EI and CQ dimensions on the new retained ENB dimensions. Hence, concerning EI, the results showed that others-emotions appraisal (OEA), use of emotion (UOE), and regulation of emotion (ROE) were the relevant variables in the context of the ENB of international top managers of international SMEs. Others-emotions appraisal is concerned with the capability for the perception and understanding of the emotions of others; the ability to predict the emotional responses of others ; the creIn relation to CQ, our results showed that its four dimensions were relevant in the context of the ENB of the SMEs’ international decision-makers. The metacognitive dimension empowers individuals with the cultural awareness that allows them to draw up cognitive strategies and enhance awareness about cultural interactions . TherefoThis study has several theoretical and practical implications for our understanding of the role that cultural intelligence and emotional intelligence plays in improving the engagement of the top managers’ external networking behavior within the international business management context.Overall, this research makes three major theoretical contributions. First, given the importance of networking within the international business management context, our study’s findings contribute to network theories suggesting that the top managers’ psychological characteristics have a central role in their external networking behavior. Second, the present study also contributes to emotional intelligence theory and to cultural intelligence theory by showing the booster value of these intelligences to the international top managers’ external networking behavior in international business contexts. Therefore, the present research makes these contributions at the confluence of the international business, networks, and psychological fields. Lastly, and adding to these theoretical bodies of knowledge, interesting theoretical implications emerged concerning the relationship between the emotional intelligence and cultural intelligence dimensions and the new retained external networking behavior’s factorial structure, as stated above.As a relatively new approach, this research adds to the literature on emotional intelligence theory, cultural intelligence theory, and network theory within the international business management body of knowledge, suggesting that the higher the levels of international top managers’ emotional and cultural intelligences, the better the performance of their external networking behavior.The results of our research are of interest to the international management field. The findings shed light on the value of the emotional and cultural intelligences of the firms’ international decision-makers. According to our results, emotional intelligence and cultural intelligence play an important role in the top managers’ external networking behavior. In line with this, we offered insights into the psychological characteristics that may play an important role in the performance of the top managers’ behaviors when building and maintaining external contacts, when using external contacts in a win–win perspective, and in the commitment to creating external contacts. These findings have important implications for international top managers’ profiles. The results showed that the higher the capability of the decision-makers to reason about emotions, to use emotional knowledge to enhance thought, and to adapt to new cultural settings, the better their chance of engaging better in their external networking behavior. In this sense, international firms that want to have capable international top managers to engage and improve their external networking behaviors should provide training programs on emotional and cultural intelligences to their major international human resources. Specific training programs should be provided to improve their different emotional and cultural capabilities.From a dimensional perspective, our findings also indicated that in order to better build and maintain their external contacts, international top managers must be aware and improve their emotional capabilities concerning the perception and understanding of the emotions of others, the use of emotions to facilitate performance, and the regulation of emotions. To this end, they could also improve their cultural capabilities concerning their cultural awareness, their cultural knowledge, and their capability to direct attention and energy to diverse cultural contexts. Our results suggest that the international SMEs’ top managers had a greater chance of using their external contacts in a win–win perspective if they invested themselves in improving their use of their emotional capability and their cultural motivational and behavioral capabilities. Concerning the commitment to creating external contacts, we encourage international managers to improve their cultural knowledge and their emotional capabilities for using and regulating emotions. Therefore, an important managerial implication concerns the fact that the two intelligences in question are trainable and might be improved by the international top managers to produce better external networking behavior. Given the importance of networking in the international business context, the organizations that are internationally active or those that are intending to approach the international markets should assess the cultural and emotional intelligences of their potential international top managers, not only when hiring new ones but also when promoting internally. These are also important intelligences for teamwork development.Thus, this research shed light on the role of the emotional and cultural intelligences of the founders, owners, chief executive officers (CEOs), managers of international activities, international market managers, or commercial managers of the international SMEs in the particular case of Portugal. Improving these intelligence levels would allow international decision-makers to enhance their external networking behavior.The importance of the relationships through networks is recognized within the SMEs’ international context . In thisIn relation to the exploratory analysis of ENB, we found three different factors that embodied an interesting approach. Hence, after the interpretation, we retained the following three dimensions: building and maintaining external contacts, using external contacts in a win–win perspective, and a commitment to creating external contacts. To deepen the analysis, we also studied the value of the decision-makers’ cultural and emotional intelligence dimensions on the external networking behavior factors used when conducting the empirical study. Important relations between CQ and EI dimensions and the new retained factor structure of ENB constituted an important result of our study.In summary, this research suggested that cultural and emotional capabilities help top managers to engage in multicultural contexts in order to achieve better results in their ENB.Regarding limitations, we emphasize the main ones, starting by mentioning that the self-report nature of the measures may lead to biases. However, its use is widely seen in the study of intelligences and external networking behavior ,28,32,48


While countries are in a hurry to obtain SARS-CoV-2 vaccine, we are concerned with the availability of vaccine and whether a vaccine will be available to all in need. We predicted three possible scenarios for vaccine distributions and urge an international united action on the worldwide equitable access. In case the international community does not reach a consensus on how to distribute the vaccine to achieve worldwide equitable access, we call for a distribution plan that includes the employees in international transportation industries and international travelers to halt the disease transmission and promote the recovery of the global economy. We are glad to see “the joint appeal” by 3,000 people and the comment on the journal ,2. We alEven under the assumption that a COVID-19 vaccine will become available in time, prioritization regarding its distribution to 195 countries and maintenance of worldwide equitable access will remain challenging . NotablyTo promote any collaborative framework discussing prioritization in access and distribution of the vaccine, it is imperative to understand that COVID-19 is an equal threat to all human societies and cannot be contained unless globally controlled. SARS-CoV-2 has demonstrated more resilient transmission capability than other viruses associated with respiratory diseases causing a single infected individual to precipitate a COVID-19 pandemic in a very short period of time ,12,13,14We as an international group of scientists call upon the world leaders to act together and develop a plan for worldwide distribution of a vaccine as opposed to multiple plans for individual countries. It is imperative that the public and government leaders understand that no single country is capable of stopping the pandemic individually and safeguard its inhabitants from repeated outbreaks, but a united front can achieve a global solution to the pandemic and, thus, prompt the recovery of the world economy.Most importantly, the successful distribution of the vaccine in one or a few countries will not stop the pandemic and will not recover global economy  15,16].,16.15,16Based on reasons mentioned above and that will be described in the subsequent paragraphs, we urge the following steps to accomplish equitable vaccine access: (1) international community to immediately start the discussion on how to form an organized approach to equitable distribution, (2) develop a vaccine distribution plan based on prioritization of needs, and (3) organize and carefully coordinate global distribution.However, in case the international community does not reach a consensus on how to distribute the vaccine to achieve worldwide equitable access, at a minimum we call for a distribution plan that includes essential people for stopping disease transmission and promoting the recovery of the global economy [ economy . Here we economy ,14,22. TBased on the Aviation Benefits Report of International Air Transport Association , around Based on the source of Wikipedia, in 2019, the world’s three biggest international air cargo companies have a total of 1,261,000 employees  . If we aBased on the reports from the World Shipping Council, the total number of direct jobs in the shipping industry is 4.2 million .Second, we recommend all international travelers receive the vaccine. Based on the world air transport statistics 2019 , in 2018We also propose to vaccinate all people working in indirect service, such as airport hotels and restaurants for the four prioritized groups, adding a population of similar size as the total number of people in the prioritized groups ,30.It is important to note that the total number of people in the first three priority categories is less than 20 million. This is less than half of the people of a middle-sized country and a small portion of the total population of China or the US. Vaccination of such a count of people in China, the US or any other country will not halt the pandemic of COVID-19 and will not improve the international business and transportation. Thus, neither the stopping of COVID-19 disease nor the economy will be improved by vaccination of these individual in a country. However, if these people in international transportation are vaccinated as we proposed, the international COVID-19 transmission will be greatly halted, and the world economy will be greatly benefited. Most importantly, as long as the world is united for it, it is realistically feasible to support such an approach and produce a globally and individually much more beneficial effect than prioritizing the complete or partial vaccination of people in a single or few countries.In conclusion, we strongly urge the international community, especially the WHO, regardless of the other considerations regarding the distribution of a potential COVID-19 vaccine, to allow the worldwide distribution of the vaccine to at least the presented priority groups and make every effort including price adjustment, shipment, resource supplement, and personal training to accomplish this target. By doing so, the world economy can begin to recover and the international spreading of the disease will be largely halted. With regard to air passengers, if vaccination becomes mandatory for travelers and the vaccine is available to them, we will be able to achieve effective infection control and regain a functional global and local economy.This article serves as a call to the public and the leaders of the world to support such an international collaboration and put the health of all humans and world economy in front of individual short-term gain.


SPG11 mutations can cause autosomal recessive hereditary spastic paraplegia (ARHSP) and juvenile amyotrophic lateral sclerosis (JALS). Because these diseases share some clinical presentations and both can be caused by SPG11 mutations, it was considered that definitive diagnosis may not be straight forward.SPG11 mutations were gathered by interviews and neurological examinations including electrodiagnosis (EDX) and magnetic resonance imaging (MRI).The DNAs of referred ARHSP and JALS patients were exome sequenced. Clinical data of patients with SPG11 mutations were identified. Two mutations are novel. Among seven Iranian probands, six carried the p.Glu1026Argfs*4‐causing mutation. All eight patients had features known to be present in both ARHSP and JALS. Additionally and surprisingly, presence of both thin corpus callosum (TCC) on MRI and motor neuronopathy were also observed in seven patients. These presentations are, respectively, key suggestive features of ARHSP and JALS.Eight probands with SPG11 mutations are suggested. The importance of performing both EDX and MRI is emphasized. Initial screening for p.Glu1026Argfs*4 may facilitate SPG11 screenings in Iranian patients.We suggest that rather than ARHSP or JALS, combined ARHSP/JALS is the appropriate description of seven patients studied. Criteria for ARHSP, JALS, and combined ARHSP/JALS designations among patients with  SPG11 mutations are described. Two previously unreported SPG11 mutations are reported. Definitive diagnosis of ARHSP or JALS is sometimes very difficult. Rather than ARHSP or JALS, combined ARHSP/JALS is the appropriate description for some patients with SPG11 mutation. Criteria for ARHSP, JALS, and combined ARHSP/JALS designations among patients with SPG11 mutations are suggested.Nineteen patients of eight families with  The gene was first identified as a major cause of autosomal recessive hereditary spastic paraplegia  in 2007 have been reported in JALS patients and mutations in the JALS gene Alsin (ALS2) have been reported as the cause of ARHSP  is a progressive and fatal motor neuron disease with an estimated prevalence of 2‐7/100000 Nelson, . Death uSPG11 mutation screening in these siblings and in 27 other ARCMT2 families without mutations in other candidate genes  disease constitutes a heterogeneous group of inherited peripheral neuropathies  data on the patients are presented. Features common to ARHSP and JALS were present in the patients of all the families. We conclude that diagnosis of ARHSP is in order for patients of one of the families, but that definitive diagnosis of either ARHSP or JALS in the remaining patients is not straightforward. They have both ARHSP and JALS presentations that may somewhat favor one or the other of the two diseases in various patients.Here, we report finding 2This research was performed in accordance with the Declaration of Helsinki and with approval of the ethics board of the University of Tehran.http://www.ensembl.org/Tools/VEP) and wANNOVAR (http://wannovar.wglab.org/). Subsequently, filtering was performed by removing SNPs with a minor allele frequency (MAF) of > 0.01 in the dbSNP database (http://www.ncbi.nlm.nih.gov/), the Trans‐Omics for Precision Medicine program (https://www.nhlbiwgs.org/), the 1,000 Genomes database (www.1000genomes.org), the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/), the Exome Aggregation Consortium database (http://exac.broadinstitute.org/), the Genome Aggregation Database (http://genomad.broadinstitute.org/), the Greater Middle East Variome Project (http://igm.ucsd.edu/gme/), ENSEMBL (https://www.ensembl.org/index.html), the Healthy Exomes database , the Sequencing Initiative Suomi database (http://www.sisuproject.fi/), the VarCards database (http://varcards.biols.ac.cn/), or the Iranome database (http://iranome.com/), or observed in in‐house exome data belonging to approximately 50 unrelated Iranians affected with non‐neurological diseases. Among the variations that remained, those that did not affect amino acid change or splicing were also removed. Finally, a file of homozygous variations and a file of compound heterozygous variations were prepared. Variations in the files were scrutinized to identify those within any of the 44 known ALS‐causing or 91 known HSP‐causing genes . EDX including NCS and needle EMG was done in upper and lower extremities, truncal regions, and cranial regions according to standard procedures . Brain magnetic resonance imaging (MRI) was performed using a 1.5‐T system . T1‐ and T2‐weighted spin‐echo protocols were performed.Probands with mutations in 33.1SPG11 and whose clinical features were carefully evaluated are shown in Figure SPG11 were reported in the exome sequence results of the proband of family SPG11‐300, and homozygous c.3075dupA (p.Glu1026Argfs*4) mutations were reported for the proband of family SPG11‐303. The filtering protocol applied by us to the whole‐exome sequence data of the probands of six families identified homozygous SPG11 mutations in five, SPG11‐101, SPG11‐189, SPG11‐210, SPG11‐301, and SPG11‐302  that we ourselves had sequenced and were also not reported in the results of SPG11‐300 and SPG11‐303 .Pedigrees of the eight families who were found to harbor mutations in 2 Figure ; Table 12 Figure ; the dat03 Table . All thes Figure . Interess Figure , usuallys Figure . Three d3.2SPG11 mutations is presented in Tables Relevant information on patients of families with 3.2.1The proband (SPG11‐300‐II1) was referred at the age of 26 years with presentations of difficulties in walking and spasticity in lower extremities. Onset of symptoms was at age of 16 years. His mental status was normal, there were no signs of bulbar involvement, sensory signs were normal, and amyotrophy was not seen. EDX evaluation was normal and there was no evidence of lower motor neuronopathy or of sensory neuropathy. Absence of motor neuronopathy in the EDX findings does not support ALS diagnosis. Brain MRI demonstrated TCC, more prominent in the rostral (anterior) region, and periventricular white matter hyperintensities. The proband had an affected 19 years old sister with similar history and presentations since the age of 17 years. We consider that the siblings have pure UMN involvement and are affected with ARHSP.3.2.2The proband SPG11‐102‐II4) had difficulty in grasping and holding onto objects, and also in performing fine tasks with his hands from age of 12 years. Stiffness and then weakness in lower limbs ensued within 1 year. His speech is low tone, but comprehensible. He does not have swallowing, hearing, or vision problems. Spinal deformity, scoliosis, and dystonic posture in the arms were evident. The patient could not continue schooling after primary school because of mental insufficiency. EDX results indicated prominent motor neuronopathy. The proband has two siblings with similar history and manifestations, except that their mental impairment was more serious, pes cavus was observed, and scoliosis was not evidenced in these individuals. Some phenotypic features that are presented here and in Table 1‐102‐II43.2.3Both affected siblings in families SPG11‐189 and SPG11‐303 are described in Tables 4SPG11 mutations in eight families with neurological diseases. Five different mutations were identified, two of which  are novel. The others have previously been reported in ARHSP  diagnosed or ARHSP‐ and JALS‐diagnosed  patients. Considering repeated observation of the p.Glu1026Argfs*4‐causing mutation in the Iranian patients of this study, it seems reasonable to first check for this mutation in SPG11 screenings of patients of this population.We have reported SPG11 mutations have also been reported in several studies . The presentations of the patients of this family including muscle weakness, stiffness, spasticity, and increased reflexes may all be attributed to UMN malfunctioning. Absence of EDX evidence for motor neuronopathy suggests the absence of LMN involvement. Definitive diagnosis of either ARHSP or AR‐JALS is difficult for the patients of the remaining families. Patients of the latter families have some presentations supportive of ARHSP diagnosis, and other features supportive of JALS diagnosis. A combined ARHSP/JALS phenotype may be a better designation for their condition. We emphasize that proposal of a combined ARHSP/JALS phenotype is related to but goes beyond recognition that pure ARHSP and pure JALS share some presentations including motor disturbance, spasticity, increased deep tendon reflexes, and long disease duration. It emphasizes that some patients simultaneously manifest presentations that are classically associated with ARHSP and also presentations classically associated with JALS. The most evident of these are presentation of TCC that is commonly associated with ARHSP and EDX evidence of motor neuronopathy that is a cardinal feature associated with JALS. Although a relatively small number of families were studied here, it is notable that the condition of the patients in the majority of the families was considered to be the combined ARHSP/JALS phenotype. The importance of correct diagnosis will become more important if effective treatment protocols become available for one or both of the diseases. Presently, riluzole and edaravone are administered only to ALS patients (https://doi.org/10.1016/S1474‐4422(18)30091‐7) , EDX evidence of motor neuronopathy is the most important feature that can determine whether LMN involvement is present (as in JALS) or absent (as in ARHSP). This feature becomes evident early in the course of the disease, and is therefore useful for early differential diagnosis. For practical application, we suggest that patients with the shared ARHSP and AR‐JALS presentations described above may be classified as ARHSP if there is no EDX evidence of motor neuronopathy but TCC is evidenced in brain MRI. They may be classified as AR‐JALS if EDX results indicate motor neuronopathy and TCC is not evidenced in brain MRI. Patients with the common ARHSP and AR‐JALS presentations and also EDX evidence of motor neuronopathy and TCC in MRI may be diagnosed with a combined ARHSP/JALS phenotype. In light of the information provided, we suggest that EDX and MRI be performed on patients for whom ARHSP or JALS diagnosis is being considered, and that the presence or absence of neuronopathy and TCC be carefully assessed.Variations in presentations of patients with The authors declare that they have no conflict of interest.MK: recruited patients and family members, analysis of exome data, performed segregation analysis in the families by direct Sanger sequencing, contributed to writing of manuscript; HS: significantly contributed to gathering clinical data, contributed to writing of manuscript; FF, MR, BHA, FHA, and SN: identified and introduced patients and provided clinical data; AA, HM, and RHSJ: analysis of exome data; HT, MTG, LJ, and SSH: performed segregation analysis in the families by direct Sanger sequencing; MH: provided clinical data, EE: designed and supervised the research, wrote the manuscript.Table S1Click here for additional data file.Table S2Click here for additional data file.


Arterial stiffness predicts the risk of cardiovascular events and all‐cause mortality and is associated with age and hypertension. However, the magnitude of the relationship between blood pressure (BP) and progression of arterial stiffness is unclear, limiting our understanding of how arterial stiffness mediates clinical effects of hypertension and planning of clinical trials.P<0.001; P value for heterogeneity=0.70), equivalent to a 1.14‐m/s increase in standard carotid‐femoral pulse wave velocity per decade per 20–mm Hg systolic BP, independent of age. Unstandardized, adjusted associations were similar , equivalent to a 0.94‐m/s increase per decade per 20–mm Hg systolic BP. In limited studies, standardized associations between mean BP and arterial stiffness progression were not significant and heterogeneous .Medline and EMBASE were searched for prospective studies reporting linear models between baseline BP and progression of arterial stiffness, with and without adjustment for demographic characteristics and baseline stiffness. Standardized and unstandardized β coefficients for pulse wave velocity were combined by fixed and random effects meta‐analysis, weighted by the inverse variance. Of 566 fully reviewed articles from 30, 524 titles, 22 populations from 21 reports were included. In 9 cohorts, there were consistent, adjusted associations between baseline systolic BP and progression of arterial stiffness (11 781 patients; standardized β=0.041; 95% CI, 0.026–0.055; Baseline systolic BP was associated with a clinically important progression of arterial stiffness, independent of age, providing a reference for the potential effect of arterial stiffness in mediating changes in clinical outcomes associated with hypertension and providing a reference value to aid clinical trial design. BPblood pressurecfPWVcarotid‐femoral pulse wave velocityDBPdiastolic blood pressureMBPmean blood pressurePWVpulse wave velocitySBPsystolic blood pressureIn this meta‐analysis, there was an estimated standardized regression coefficient of 0.041 between baseline systolic blood pressure and progression of aortic stiffness, which translates to a 1.14‐m/s increase per decade in standard carotid‐femoral pulse wave velocity for every 20–mm Hg systolic blood pressure.Clinical harms caused by hypertension may partly be mediated by progression of arterial stiffness over time, independent of age, sex, and cardiovascular risk factors, a relationship that is large enough to be clinically significant over time.Reducing hypertension early has the potential to prevent progression of later‐life arterial stiffness and therefore associated clinical sequelae, and this relationship should be considered in clinical practice and clinical trial design.Arterial stiffness is a robust predictor of cardiovascular events and mortality, independent of other risk factors, with a 1‐m/s increase in carotid‐femoral pulse wave velocity (cfPWV) associated with an increased risk of cardiovascular events, cardiovascular mortality, and all‐cause mortality by 14%, 15%, and 15%, respectively.Arterial stiffness is most strongly associated with age and hypertension in cross‐sectional studies,Therefore, we performed a meta‐analysis of the magnitude of association between elevated BP and progression of arterial stiffness.EMBASE and Medline were searched between inception and May 24, 2019, to identify longitudinal studies reporting an association between BP and progression of arterial stiffening Data . AccepteExtracted primary effects included associations from general linear models between baseline BP  and progression of arterial stiffness, including both standardized and unstandardized β coefficients, either unadjusted or adjusted for demographic covariates and/or baseline arterial stiffness. Other extracted variables included demographics of the included population , study characteristics , inclusion/exclusion criteria, length of follow‐up, loss to follow‐up, conclusions, method and frequency of stiffness measurement, and details of analytical models . Measures of uncertainty of all variables were extracted where available, including SD, SEM, or interquartile range.SD=SE×n), interquartile range (SD=interquartile range/1.35), or, for the change in arterial stiffness, from the SD of arterial stiffness at baseline and follow‐up (SDΔ=SD12+SD22), always taking the more conservative method of estimating the SD. Where studies reported population characteristics by subgroups, weighted means between subgroups were used to estimate mean values  for the population as a whole. P values reported in this review are derived from the estimated CIs, so they may differ from those reported in the original articles.Where only unstandardized β coefficients were reported, standardized β coefficients were calculated by multiplication of the unstandardized β coefficient by the ratio of the reported SD of the BP at baseline and the SD of change in arterial stiffness, with the opposite transformation for converting standardized β coefficients to unstandardized coefficients. Unstandardized β coefficients were transformed to the standard cfPWV, as defined by 80% of the distance between the carotid and femoral measurement site,Regression coefficients from unadjusted and adjusted analyses were combined by fixed and random effects meta‐analysis, weighted by the inverse variance.j=(nj/Σn)×(Σinverse variancei…n×ni…n)). Sensitivity analyses were performed without imputation and following adjustment for publication bias by trim and fill of smaller studies >1 SD from the summary estimate. Heterogeneity was assessed by I2 statistics and χ2 tests for heterogeneity. The meta‐analysis protocol was published on PROSPERO  before data extraction, with subsequent focus on BP alone because of insufficient reporting of other modifiable risk factors from the same studies.Where the inverse variance for a β coefficient could not be estimated from reported information, an inverse variance was estimated from the ratio of the study size to the size of all studies in which the inverse variance was known, multiplied by the sum of the product of the inverse variance and study size for each study in which the inverse variance was known , with no significant heterogeneity between studies , including after exclusion of the study reporting carotid‐radial PWV . This association was consistent for studies assessing cfPWV or brachial‐ankle PWV , and the effect was similar when excluding studies that also reported unstandardized coefficients .In 9 populations including 11 781 participants, there was a consistent standardized association between baseline SBP and increase in arterial stiffness in adjusted linear models , particularly because of limited interventional studies reporting negative correlations. On restricting the analysis to noninterventional studies, there was no significant heterogeneity and a consistent positive association between SBP and progression of arterial stiffness , corresponding to 0.94‐m/s cfPWV per 20–mm Hg SBP per decade, with no significant heterogeneity. Associations were similar when excluding studies where measures of uncertainty were imputed .There was a similar magnitude of effect in studies reporting unstandardized, adjusted β coefficients between SBP and progression of cfPWV  between studies reflecting variation in population characteristics and adjusted covariates. However, there was no statistically significant difference in the association between baseline SBP and progression of arterial stiffness when comparing studies with a mean age of <50 years compared with studies with a mean age of >50 years , or for the interaction between mean age and the association between baseline SBP and change in PWV in a metagression (P=0.28). Furthermore, sensitivity analyses including only studies that adjusted for both baseline age and baseline arterial stiffness were highly consistent, with similar effect sizes to the primary meta‐analysis . As such, pulsatile blood flow may be more important in driving increases in arterial stiffness caused by either a greater intermittent maximum pressure or a greater shear stress, rather than the total BP burden. Unfortunately, studies did not report associations with pulse pressure compared with mean pressure to assess this more directly. Also, despite the temporal order of the relationship, it is still possible that these associations are caused by reverse causation, with elevated arterial stiffness inducing a decreased DBP and increased SBP, reflecting an increase in pulse pressure  attributable to increased reflection of the cardiac pulse wave from the peripheral circulation.This review has some limitations. First, there was limited quantitative data available for both MBP and DBP, limiting the strength of conclusions as to the relative effect of the pulsatile (SBP) and the constant (MBP/DBP) components of BP, although the strength of association with SBP compared with available MBP data suggests that a significantly greater association with MBP is unlikely. Second, there was a large variation between studies in reporting of method of measurement, population characteristics, and adjustment for confounding variables. However, there was little heterogeneity between studies in estimates of the standardized β coefficient, after adjustment for age in particular. Third, studies varied in reporting of estimates of uncertainty. As such, these measures were conservatively estimated or imputed from available information, resulting in a potential underestimate of the precision of the meta‐analysis. However, sensitivity analyses in the more completely reported studies showed similar effect sizes. Fourth, there was a limited number of studies for each outcome measure, preventing stratification of analyses to identify interactions with SBP by age and sex.This study provides a reference value for further studies to determine the magnitude of the effect of hypertension on progression of arterial stiffness and therefore the maximum potential effect of antihypertensive treatment mediated by BP reduction. This supports calculation of the power required for clinical trials to prevent progression of arterial stiffness where previous estimates of the direct effect of interventions are not available, both for antihypertensive medications and for other treatments. In addition, it provides a reference value to compare the relative effect of different classes of antihypertensive medications on arterial stiffness, and whether the demonstrated effect is as could be expected for the achieved reduction in SBP or whether non–BP‐mediated effects may be important. However, further studies are required to determine whether the estimated effect size is consistent between different demographic groups and provide a better estimate of the association with MBP or DBP and progression of arterial stiffness.This study provides the best estimate of the relationship between elevated SBP and progression of arterial stiffness, demonstrating consistent associations across independent studies, equating to approximately a 1‐m/s increase in PWV per 20–mm Hg SBP per decade. This is of sufficient magnitude to be associated with approximately a 15% greater relative mortality per decade. It therefore provides a reference to understand the potential role of arterial stiffness in mediating the clinical effects of hypertension, as well as the potential long‐term benefits of blood pressure lowering on clinical events through control of arterial stiffening, in addition to the impact of age. Finally, as the most accurate estimate available, it provides an expected effect size for determining sample sizes for future trials of agents to reduce progression of arterial stiffness. However, although this association may imply a greater importance of pulsatile hemodynamics in determining progression of arterial stiffness than the constant components of BP, further research is required to accurately determine the association with MBP and DBP, to reliably exclude an age‐dependent modification of these associations and exclude the possibility of reverse causation.This study received no specific funding. Dr Webb is funded by a Wellcome Trust Clinical Research Career Development Fellowship (206589/Z/17/Z) and a British Foundation Project grant (PG/16/38/32080).None.Data S1Tables S1–S3Figures S1–S6ReferencesClick here for additional data file.


The world does not have too much time to ensure that the fast-growing population has enough land, food, water and energy. The rising food demand has brought a positive surge in fertilizers’ demand and agriculture-based economy. The world is using 170 million tons of fertilizer every year for food, fuel, fiber, and feed. The nitrogenous fertilizers are being used to meet 48% of the total food demand of the world. High fertilizer inputs augment the reactive nitrogen levels in soil, air, and water. The unassimilated reactive nitrogen changes into a pollutant and harms the natural resources. The use of controlled-release fertilizers for slowing down the nutrients’ leaching has recently been practiced by farmers. However, to date, monitoring of the complete discharge time and discharge rate of controlled released fertilizers is not completely understood by the researchers. In this work, corn starch was thermally processed into a week gel-like coating material by reacting with urea and borate. The granular urea was coated with native and processed starch in a fluidized bed reactor having bottom-up fluid delivery system. The processed starch exhibited better thermal and mechanical stability as compared to the native starch. Unlike the pure starch, the storage modulus of the processed starch dominated the loss modulus. The release time of urea, coated with processed starch, remained remarkably larger than the uncoated urea. The world does not have too much time to ensure that there is enough land, food, water, and energy for the fast-growing population. The United Nations warns that if humans remain unsuccessful in curbing overpopulation, more than three billion people will be in poverty in coming years. The growing food crisis also presents an opportunity for researchers and investors in the farming sector, especially in fertilizer production, to invest more in this profitable business. The rising food demand has also brought a positive surge in the fertilizer demand. Due to large input of mineral fertilizers, the global production of crop and livestock has increased significantly over the past century. As revealed by the International Fertilizer Association, the world uses 170 million tons of fertilizer every year for food, fuel, fiber, and feed. Among this, the nitrogenous fertilizers are being used to meet 48% of the total food demand of the world2. Over-fertilization augments the pollutants’ level in the soil, air and water. The excessively available nitrogen during fertilization of crops also contributes to environmental pollution. The unassimilated reactive nitrogen acts as a pollutant and harms the natural resources.The world is facing the problem of exponential population growth. The population of this planet was around 3 billion in 1960, which is expected to reach 9 billion in 20403. The nitrogen cycle in terms of fixation, ammonification, nitrification and denitrification is explained in Fig. 4. Nitrogen fertilizers, nitrogen in foods and airborne nitrogen emissions are the three main sources of reactive nitrogen. The food products represent the major part of reactive nitrogen (38–75%) in the world. The airborne emissions of ammonia and nitrogen oxides, and the subsequent deposition from the atmosphere contribute about 11–36%, while nitrogen fertilizers contribute about 11–32% to the reactive nitrogen5. The surplus reactive nitrogen can cause pollution problems in the environment, such poor air quality, acidification of lakes and rivers, disruption of foresting process and degradation of coastal water quality.Most of the pollution in the world today is caused by human beings. The contribution of nitrogen to the environment pollution is increasing with growing human population. Sources of manmade pollution include excessive fertilization of crops, sewage, stormwater, industry, automobiles, burning of wood and fuels, etc7. A better understanding of denitrification and dynamics of nitrogen transformation associated with it are crucial. Nitrate is the main nitrogen species for loss of nitrogen and is influenced by several nitrogen flows that produce and consume 2). The key biological pathways of 2 and (iii) dissimilatory 8. Dissimilatory reduction can result in denitrification under limited conditions and provide an energetically favorable alternative to denitrification9. Nevertheless, there is still a need for further work to recognize the importance of DNRA in terrestrial systems and to understand perfect methods for studying the mechanism.A core process in nitrogen cycle is denitrification, a heterotrophic process carried out by facultative anaerobic organisms which use various C substrates as donors of electronsmentclass2pt{minim10. Ţolescu and Iovu11, revealed that a controlled-release fertilizer contains at least one nutrient, which delays its availability to plant after application, or available to plant over a substantially longer period of time than a normal quick release fertilizer. Shaviv12 criteria for a controlled-release fertilizer is that the factors affecting the release rate, release pattern and release time should be well understood and controllable during preparation of a fertilizer.Researchers are trying to investigate the different methods and mechanisms to minimize nitrogen losses, particularly due to fertilization. The performance of a fertilizer can be enhanced through many ways, including nitrification inhabitation, urease inhabitation and controlled-release fertilizer. Farmers around the world have recently explored the use of controlled-release fertilizers to slow down leaching of the nutrients. The added advantage of such fertilizers is the controlled availability of nutrients in the soil for longer time periods. The acceptable properties of a fertilizer to qualify as a controlled-release fertilizer vary from researcher to researcher. Under ambient conditions and absence of any external stress, Trenkel guidelines for slow release fertilizer are: (i) no more than 15 percent release within 24 hours, (ii) no more than 75 percent release within 28 days, and (iii) at least about 75 percent release after specified timeframe14. The coated layer acts as a semipermeable or impermeable membrane having tiny pores. This membrane temporarily isolates the core from the surrounding environment15. The leaching of nutrients from the membrane barrier depends on the properties of the material17. The leaching process is not much affected by salinity, pH, texture, microbial activity and cation exchange capacity of the soil. It reveals that monitoring of nutrients’ leaching from the coating membrane is not a trivial case.A controlled-release fertilizer is generally produced by coating the granular fertilizer and producing a physical barrier at the surface to control the water penetration into the core. The release of nitrogen from the coated core slows down and the farmer gets good fertilizer performance. One determined advantage of the coated fertilizers is availability of the nutrients to the plant for longer periods of time. The rate of nutrients’ leaching normally depends on properties of the material. The common materials, reported in the past literature, are neem, resins, sulfur, natural carbohydrate polymers and synthetic polymers19. Starch, lignin and cellulose have limited controlled release characteristics due hydrophilicity22. Other coated fertilizers use thermoplastics, ethylene-vinyl acetate or surfactants as diffusion retardent materials. Some zeolite-based controlled-release fertilizers have also been developed. Bansiwal et al.23 used surfactant-modified zeolite to coat Phosphorus fertilizers. Notario et al.24 prepared Phosphorous and Potassium slow release fertilizers from concentrated solutions of Potassium Dihydrogen Phosphate and Dipotassium Phosphate. Other coating materials include soda flax lignin25, graphene oxide films26 and gypsum plaster19. Gonzales et al.27 reported some polymeric materials for slowing down the urea hydrolysis. These polymers include ethyl cellulose, acetate cellulose and sodium alginate. Solihin et al.28 incorporated K+, NH4+ and PO4− ions in kaolin structure as nutrients for plant. Costa et al.29 coated urea with polyhydroxybutyrate and ethyl-cellulose in the presence of different emulsifiers.Many research efforts are underway to understand the release time, release rate and mechanism of interaction of coating with water in the soil. Sulphur coated fertilizers are costly and the coating cracks easily because of its friability30. The high toughness, chemical resistance, flexibility and abrasion resistance of polyurethane make it an attractive material for coating applications. The reported literature shows that materials containing urea or urethane groups within the backbone are gaining more significance in coating industry31. Although, synthetic polymeric coating materials have shown several merits over natural polymers32, these materials form impermeable or semi-impermeable membranes of tiny pores. The main issue in producing the polymer coated urea is the choice of right material for coating and the associated coating process33. The release of nitrogen through a membrane is mainly influenced by physical and moisture permeability properties of the coating. The soil properties did not influence much the release rate. The moisture permeability of the coating materials may be regulated by altering their composition. Therefore, the nutrient release from a polymer-coated urea can be predicted much more accurately over a given period of time than that covered with inorganic materials33. Most of the used polymers, however, are quite costly and non-degradable, so emphasis should be on low-cost, environmentally friendly polymers. The presented work is focused on the thermal processing of corn starch into a coating material using di-sodium tetraborate and urea.Polyurethane is also a versatile polymeric material first developed in 1930s for use in aerospace and military industries34. The specific rheological properties, needed to improve the adhesion and coating properties, are often incorporated through chemical modification of the starches. Chemical modification of the starch produces esters and ethers35. A chemical reaction also gives anionic or cationic character to the starches. Through chemical modification, the starches receive additional properties enabling their applications in foods industry and various technical sectors.Corn starch is a low cost, biodegradable and eco-friendly carbohydrate polymer. In the presented work, processed corn starch was used to produce controlled-release urea. To reduce the process cost, the starch with terminated shelf life can also be tested for the stated purpose. Since pure starches show poor mechanical strength, tacking ability and viscosity, they can not be used to produce good water retardant coatings36. In the given work, de-ionized water was used as a standard solvent. The solute was a premix of corn starch, urea and borate (Na2B4O7.10H2O). Corn starch was commercial grade product whereas the Analytical Reagent (AR) grade chemicals were supplied by R and M Chemicals. Four compositions of the coating material were formed and tested for their rheological, physical and slow release coating properties. The coating material was prepared by adopting the procedure of Naz et al.37. The details of formulation of coating material and processing temperature are presented in Table Comprehensive alteration of physical and chemical properties of pure starches is possible through their reaction with various chemical regents. These chemical additives convert a pure starch system into a long chain biopolymer complex of improved viscosity, tacking ability, mechanical strength and surface tension. The interactions can be intra or intermolecular or both, depending on nature, length, groups, hydration capacity, degree of polymerization, salinity, pH and co-solvents. Since polymeric chains in a starch are more flexible than polymeric chains in cellulose, starches are highly soluble in many solvents Na2B4O7.0H2O. CorOnce the physical parameters of the coating material were fully depicted, it was coated over granular urea in a conventional fluidized bed spray coater. In the coating reactor, as shown schematically in Fig. Both the uncoated and coated urea samples were inspected for coating thickness, percentage of coating material, coating morphology, nutrient discharge rate, complete dissolution time, and coating strength. Scanning electron microscopy was used to elaborate the surface morphology and coating thickness of the coated urea. The crushing strength of the urea samples was measured with a tablet tester. The crushing strength was measured in terms of constant force (N). The force required to crack the coating is called coating sensitivity. A dissolution rate test was conducted to measure the discharge time of the uncoated and coated urea. In this test, the urea was released in distilled water under a shear rate of 200 rpm. Both coated urea and control were weighed to 10 g and placed in separate glass beakers. A total of 200 mL of deionized water was added to the sample and the urea-water mixture was stirred at room temperature by using an overhead stirrer. The time for complete release of urea in distilled water was noted.This article does not contain any studies with human participants or animals performed by any of the authors.38. The possible changes in the viscosity of the modified and native starches over time are reported in Fig. 0 sample achieved maximum viscosity at a constant heating temperature of 80 °C. The viscosity of the native starch suspension was reduced by 34 points when the suspension was further heated after 15 min. After 25 min, the suspension viscosity remained unchanged over time. the peak viscosity of S0 was measured about 300 cP. Other samples also showed similar viscosity plots. The peak viscosity of S1, S2, and S3 samples was found relatively higher than the pure starch. The viscosity curves of these samples attained the peak values slightly later than the peak value of native starch. The lessening of viscosity of the modified starch after attaining the peak value had not been as noticeable as in case of pure starch.The processing conditions notably change the time and temperature of gelatinization of the starch suspension39.The alleviation of viscosity with time from the peak value might be ascribed to high process temperature and prolonged heating of the suspension. Because the temperature of decomposition of the starch granules is reported as lower than its melting point, the granules rapidly expand and crack over time. Figure 40. Figure 3 sample gained the highest viscosity among the investigated samples. The high viscosity was attributed to addition of di-sodium tetraborate in the dispersion, which dissociated into borate and sodium ions. The reactive borate ions formulated the polymer chains through hydrogen bonding with the starch whereas the charge on the developed chains was shielded by the free Na+ ions.The suggested viscosity breakdown in Fig. 0 and S3 samples is provided in Fig. 3 over S0. The pure starch destabilizes after 300 seconds, which suggests low stability of material over time. The gel of native starch breakdowns more sharply over time. In contrast, the modified samples retained their gel structures over longer periods of time. Strain sweep also reveals that after critical strain, the samples behave like a fluid (G′ < G″). It is an indication that beyond the critical strain, the material response is more complex and is no longer a function of strain alone but G′ and G″. Figure A comparison of the storage modulus of S10. The amount of coated material influences the surface morphology and release parameter of the product. The coating content depends on the physical and chemical traits of the coating material and the process parameters. In this work, the coating morphology and surface properties of the finished product were studied from SEM micrographs. As a thick layer of coating material was formed on the surface of urea granules, 20 granules from each sample were randomly selected and scanned through SEM technique. Figure The coating content typically accounts for 3 to 15% of the weight of the finished product0, S1, S2 and S3 materials, clearly differ in terms of surface morphology. As shown in Table 0 material produced the thin coating layer, whereas S3 produced the thickest coating layer among the tested materials. The coating percentage of S3 material was higher than all other tested materials.High surface roughness was seen in SEM micrograph of uncoated urea. Without coating a layer, the surface was less rigid and highly porous. Compared to uncoated urea, surface of the coated urea was highly dens and smooth. The coated surface also looked hard, uniform, compact and water resistant. SEM micrographs of the samples, coated with S42. The researchers are still designing a standardized method for commercial purposes to test the slow release fertilizers. The laboratory methods under controlled conditions are however the best and easiest way of screening the slow release fertilizers quickly11. In this work, dissolution rate testing of the coated and uncoated urea was performed in water. In a beaker, 10 g of each urea sample was taken, and 200 ml of deionized water was also added to the system. At room temperature, an overhead stirring at a constant speed of 200 rpm agitated the water-urea mixture. The time of complete dissolution of each sample was noted, as shown in Fig. 3 material was relatively greater than those coated with other rest of the materials. Shi et al.43 coated the urea with a mixture of plastic and starch and revealed prolonged nitrogen release time as compared to the pure starch coating.Different methods are available for testing the controlled release fertilizers, including the laboratory, greenhouse, growth chamber and field methods44. The mechanical resistance was measured by firmly pressing on the individual coated granules and observing the surface cracks. The mechanical strength greatly depended on the coating composition and thickness. The uncoated urea granules and those coated with S1 and S2 exhibited very low mechanical strength as compared S3 coated urea. In addition, the surface strength was considerably improved with an increase in the coating thickness to a certain point (0.54 mm), after which the coating thickness was not significantly influenced. The overall mechanical strength of coated urea varied from 22 N to 20 N. The uncoated urea exhibited the coating strength of 20 N.In addition to the above stated parameters, the coated product should also show adequate mechanical resistance to normal handling and storage for avoiding the surface fractures3 coated urea gained the highest viscosity among the investigated samples. SEM analyses showed a less dense surface morphology of the uncoated urea with a high degree of roughness. The porosity of the uncoated granules was also quite high compared to the coated granules. The surface of the coated granules was uniform, dense, and hard with low porosity. Fast release of the uncoated urea was predicted compared to the coated samples. The uncoated urea was completely released into water after 6 min. Conversely, the slowest release was predicted from the urea coated with the S3 material. The coated granules exhibited the highest crushing strength of 30 N, which was noticeably higher than the crushing strength of the uncoated urea (20 N).High urea inputs raise the level of reactive nitrogen in the soil, air, and water. Unused reactive nitrogen acts as a pollutant and harms the natural resources. The use of controlled-release fertilizers for slowing down the nutrients’ leaching has recently been practiced by farmers worldwide. The added advantage of such fertilizers is the availability of controlled amount of nutrients in the soil for longer periods of time. However, to date, monitoring of the complete discharge time and discharge rate of controlled released fertilizers is not completely understood by the researchers. The starches, modified with urea and borate, showed good stability and mechanical strength over time. A decrease in the storage modulus of the native starch showed unstable gel structure, which may break after some time. The viscous component dominated the elastic component at lower angular frequencies for the native starch. A small difference between the peak and end point viscosities of the modified starch suggested that the presence of urea and borate in the starch suspension considerably reduced the starch cracking. The S


The authors are grateful to the Editor for allowing them the opportunity to publish this Corrigendum, and wish to apologize to the readership of the Journal for any inconvenience caused.


The hydrogel formulation was applied as a carrier for escin included in the dry extract of Aesculus hippocastanum. Six hydrogels were evaluated  with various concentrations of the modified starch. The kinetic studies of in vitro β-escin release were carried out in purified water at 37 ± 0.5 °C using a paddle apparatus at 50 rpm and a time period of 7 h. The criterion for the most suitable model was based on a high correlation coefficient of evaluated release profiles. The addition of modified annealed acetylated potato starch resulted in prolongation of β-escin release.Naturally sourced products introduced to human nutrition and rediscovered for therapy include polysaccharides from potatoes. The starch may obtain unique properties via acetylation with acetic anhydride at 13 cm Modern pharmaceutical technology is based, among others, on different carriers of medicinal substances, including synthetic and natural polymers. Among the latter, the high availability in plant sources should be considered an advantage, but the disadvantage is the variability of the composition, depending on the origin of the raw material. Starch and cellulose are known as very common natural polymers ,2. PreviAn example of physical modification of starch is hydrothermal treatment, which includes annealing, i.e., native starch incubation with an excess of water at a temperature between the glass transition temperature and the initial gelatinization temperature. The purpose of this transformation is to receive such a modification temperature that stimulates the molecular mobility of starch molecules without transforming them to the gelatinized form. This process leads to an increase in the homogeneity and stability of the crystal structure of hardened starch, thereby protecting the structure of the final products ,5. The pEscin is the main active pharmaceutical ingredient in a horse chestnut seed (EH). It occurs as a mixture of triterpenoid saponins, existing in two forms, α-escin and β-escin (βE). They are characterized by different melting points, specific optical rotation, solubility in water and hemolytic index. βE is the major active component, and may be transformed into α-escin at elevated temperatures . The appThe aim of the study was to evaluate the influence of the modified acetylated potato starch polymer (MSA) addition on the release profile of βE, depending on the amount of MSA added, and the type of basic hydrophilic gel, preformulated for the topical application.A previous study on release kinetics from hydrogel formulations has been used, and the same cellulose and acryl derivatives polymers have been explored . The preAesculus hippocastanum seeds  from Herbapol S.A.  was used as a model medicinal substance. The modified acetylated potato starch polymer (MSA) from the University of Environmental and Life Science  was used at 20% and 40% as a studied component of the gels.The following polymers were used as hydrogel components: Methylcellulose , Carbopol 980 NF  and polyacrylate crosspolymer 11 . The thick extract of The composition of the prepared gels is shown in 3/100 g of starch as the basic dose of reagent used in industrial conditions. After drying the acetylated starch, an initial gelatinization temperature of 49.17 °C using a Mettler differential scanning calorimeter was determined [A large starch knob fraction with an average volume diameter D4,3) equal to 61.7 µm was isolated from natural potato starch with an average volume diameter D of 39.1 µm, determined using a Malvern laser particle size analyser [,3 equal termined . Two lit2. Purified water was used as a dissolution medium in a volume of 900 mL at 37 ± 0.5 °C [The release kinetics study was performed in a drug dissolution Tester Erweka GmbH DT 700  paddle-over-disc apparatus using the pharmacopoeial method at a stirring rate maintained at 50 rpm. A dialysis tubing cellulose membrane 43 mm × 27 mm in size with pores of 14 kDa  was applied to the extraction cells with an area accessible to the dissolution of 28.26 cm± 0.5 °C ,11,12,13± 0.5 °C ,16, acco± 0.5 °C . The Wei± 0.5 °C . J is the amount of solute passing through a unit area perpendicular to the surface per unit time, D is the diffusion coefficient, and dC/dx is the concentration gradient, which represents a driving force for diffusion [The models applied in the study  come froiffusion . There aiffusion . The firiffusion ,20. In siffusion . The Weiiffusion .The initial amount of EH in the formulations is presented in The flow of first-order kinetics model function indicated a departure of linearity, especially applied to formulations with PC-11 .The charts for the second-order kinetics model were well suited to the linear course of the function, especially used to formulations with MC .The Higuchi model best reflected the course of reactions with PC-11 hydrogel .The logarithmic equation of the Weibull model introduced a good fit for the rectilinear course of graphs .Additionally, the probable course of release reactions in the Weibull model was statistically adjusted .−2 %·min−1 to 9.50 × 10−2 %·min−1 starcConsidering the aqueous conditions of the reaction, there is a likelihood of hydrogen bonds between the carbonyl groups of MSA and βE .−2 %·min−1 and 9.50 × 10−2 %·min−1 for the zero-order kinetics and between 4.93 × 10−4·min−1 and 1.29 × 10−3·min−1 for the first-order kinetics. For the second-order kinetics, they were between 5.59 × 10−6 %−1·min−1 and 1.80 × 10−5 %−1·min−1, and for the Higuchi model, they were between 1.05 %·min−1/2 and 2.31 %·min−1/2. The highest values of release rate were observed in the case of the formulations with MC, and the lower values were similar to each other in the case of the preparations with PA1 and PC-11. MC was applied in the formulations F0, F20, and F40. MC exhibits water- and organo-solubility and thermal gelation properties. Its wide range of viscosity  corresponds to an average molecular weight range of 10,000–220,000 Da, making it useful as a carrier, a coating agent, and a disintegrant for tablets and matrix tablets [The most interesting parameter which reflects the expected release prolongation is the half-release time calculated on various equations according to available sources . The rel tablets . MC 0512 tablets , Berger  tablets . The aboAccording to the Weibull model, a β-factor has been established . The ranThe influence of MSA concentration in the evaluated hydrogel formulations on the release rate of βE was confirmed. The formulations of MSA with MC (F40) and PA1 (G40) had the highest impact on the release prolongation. The highest release prolongation was obtained in the formulation G40 containing PA1 and MSA. The PC-11 (H0) itself decreased βE release, whereas, the MSA addition slightly influenced the process (H40). Studies are still needed on the mechanism of binding the active substance to the PC-11 hydrogel, as there may exist strong interaction of βE with the polymer, presumably via the amide bonds. This may be ascribed to the presence of amide groups bonding to the carboxyl groups of βE and carboxylic groups interacting with polar solvents, such as water. The best fit of βE release pattern belonged to second-order kinetics and the Higuchi models. The Weibull model adapted to the experimental data. The appearance of β-value between 0.5 and 1.0 pointed to the mixed mechanism of the occurred processes.