Cercocebus atys atys) and western chimpanzees (Pan troglodytes verus), we tested what properties of potential partners influenced grooming decisions, including their relative value based on available alternatives and the social relationships of potential partners with bystanders who could observe the outcome of the decision. Across 1529 decision events, multiple partner attributes  influenced choice. Individuals preferred to initiate grooming with partners of similar global rank, but this effect was driven by a bias towards partners with a high rank compared to other locally available options. Individuals also avoided grooming partners who had strong social relationships with at least one bystander. Results indicated flexible decision-making in grooming interactions in both species, based on a partner's value given the local social environment. Viewing partner choice as a value-based decision-making process allows researchers to compare how different species solve similar social problems.Living in permanent social groups forces animals to make decisions about when, how and with whom to interact, requiring decisions to be made that integrate multiple sources of information. Changing social environments can influence this decision-making process by constraining choice or altering the likelihood of a positive outcome. Here, we conceptualized grooming as a choice situation where an individual chooses one of a number of potential partners. Studying two wild populations of sympatric primate species, sooty mangabeys ( To balance short- and long-term costs and benefits, animals have to decide when and how to interact with conspecifics so that the choice yields higher profit than an interaction with a random partner . IncreasPrimate grooming has been interpreted as an important commodity that can be exchanged for other services –17. GrooPrimate grooming interactions thus represent an ideal opportunity for examining the flexibility of the decision-making process underlying partner choice. Market theories predict that individuals adapt their partner choice to the local social environment which determines the supply ,14; for In grooming, bystanders can impact the outcome of interactions by actively disrupting or joining grooming , or by iThe presence and absence of group members can influence grooming interactions by changing the relative value of a commodity a partner has to offer ,36. PrevCercocebus atys atys) and western chimpanzees (Pan troglodytes verus) both live in large multi-male, multi-female societies, but with social systems that should differ in terms of the impact of the social environment on cooperative interactions. Sooty mangabeys are female philopatric, probably matrilineal [Sooty mangabeys  and field assistants for the Taï Chimpanzee Project's long-term database. Dominance ranks of all communities were calculated using a modification of the Elo rating method  with withglobx  with bin = 1529 grooming initiations over n = 8809 potential partners. We tested whether those individuals who were chosen differed significantly from those who were not, and if there were group differences. Model 2, focusing only on the chimpanzees, consisted of n = 1372 grooming initiations and n = 7781 potential partners. We tested whether chimpanzee males and females followed the same patterns when choosing grooming partners.The impact of partner rank can occur on two levels: Individuals have a global rank that describes their status in the community, and a relative rank in the party, capturing shifting partner value based on availability. The global and relative ranks are highly correlated and can therefore not be included in the same model; however, they might still vary in meaningful ways. For example, only 6 out of 52 potential partners in our sample were ever the highest-ranking individual by global rank, but 27 individuals at some point held the highest relative rank in the party. The same was true for the global and relative relationship strength. We fitted both Model 1 and Model 2 twice, once with the global ranks and DDSI of focal individual and partner, and once with their relative ranks and DDSI. We can use differences between global and relative rank/DDSI models to understand whether focal individuals represent potential partners independent of the social environment , or whether they represent individuals flexibly based on the availability of other options . We thus created two models to test the effect of multiple dimensions on grooming partner choice, and fitted each of them twice, using the global and relative variables, respectively. Model 1 consisted of each combination of grooming bouts with all potential partners for N = 32) and potential partners (N = 52), and their dyad combinations (N = 342) in models as random effects [n = 20 cases) and females with young offspring in East (n = 36 cases) led to relative uncertainty in the estimates for these variables in interaction with group identity.We included the identities of the focal individual . In the Global Model, the interaction between the squared global partner rank with global focal rank  and the three-way interaction between global partner rank, global focal rank and group  were significant. Taken together, these interactions revealed that in the mangabeys, there was an attraction to closely ranked partners, especially in high-ranking individuals (a). In the East community, low-ranking initiators targeted medium-ranked partners, while medium- and high-ranking initiators focused on closely ranked partners. In the South community, individuals targeted closely ranked partners, and this effect was stronger in low-ranking individuals. In the Relative Model, no interactions of rank were significant and the main effect of relative partner rank revealed that focal individuals in all three communities targeted partners who were high-ranking within the party .The full null model comparisons of both models using global and relative rank for all three communities were significant . Focal individuals in all groups targeted close social partners for grooming, but this effect was more pronounced in the mangabeys (a). There was also a significant main effect for the reproductive state of the partner in the Global Model  and the Relative Model . In both chimpanzee communities and the mangabeys, focal individuals preferably initiated grooming with females with infants less than 3 months of age .Both models showed a significant interaction between global/relative relationship value and group, respectively . Focal individuals preferably targeted individuals with whom they had an aggression in the 30 min prior.There were no group differences related to the effects of the bystander relationships in either model. The maximum DDSI of partner . The results for global ranks matched those of Model 1 . For the relative rank, male chimpanzees continued to show attraction to individuals with high relative rank, while females showed a bias towards individuals who were close to them in relative rank . Both models showed a significant interaction between the relationship value of the dyad and focal sex , with female chimpanzees targeting partners with whom they had a closer social relationship, while males did not or only weakly show this effect (b). The maximum DDSI of the partner in both models showed no sex differences and results matched those of Model 1. The effect of previous aggressions also matched the results of Model 1. In the Global Model, we found a significant interaction between the sex of the focal and the sex of the partner , with females in both communities preferably initiating grooming with males, but no specific preferences in males. In the Relative Model, there was a significant interaction between the two sex variables and group identity , indicating that while the aforementioned effect persisted in the East community, there were no preferences of focal individuals for either sex in South.The full null model comparisons of both the models using global and relative rank for the two chimpanzee communities were significant (Global Model: s effect b. The ma4.In this study, we conceptualized grooming as a decision-making event where individual chimpanzees and sooty mangabeys selected a partner from a group of available individuals. This allowed us to test the flexibility of grooming partner choice with regard to the number of variables both species integrate. We found that multiple partner attributes had an impact on partner selection, but also that the availability of alternative partners and their relationships influenced partner choice. Individuals avoided grooming partners that had strong social relationships with at least one bystander, suggesting these primates use flexible decision-making that assesses a partner's value given the local social environment. Partners are associated with different benefits and risks, and it seems that individuals in both species flexibly distributed their grooming to maximize benefits and minimize costs.Our results suggest that focal individuals in both species incorporated a number of different variables into their grooming decisions. Females in both species preferably initiated grooming with potential partners with whom they already had a strong social relationship, either due to a preference for bond partners  or as reIn both species, the wider social environment also influenced partner choice. Groomers in mangabeys and South chimpanzees focused their efforts on individuals that were close in global rank, as did medium- and high-ranking individuals in East chimpanzees, while low-ranking individuals in East chose medium-ranked partners. However, locally, focal individuals in both species preferably initiated grooming with individuals that had a high relative rank compared to other potential partners. Only female chimpanzees also preferred partners with a similar relative rank. This divergence between the two rank variables indicates that either, initiators were attracted to the highest-ranking individual available , but assThe presence of close social partners of a grooming target might make it more likely that these individuals intervene into the grooming bout  or that Though we predicted species differences in the bystander variables and the impact of rank on partner choice, due to the differences in hierarchy steepness ,100 and When discussing the cognitive requirements facing cooperating animals, researchers have focused on the challenge of representing previous interactions of the cooperators ,101. Her


We aimed to find the exposure level of triclosan (TCS), a known endocrine disruptor, related to the use of personal care products using a nationally representative data of the general population in Korea.This study included data of 6288 adults aged 19 years and older , based on the Second Korean National Environmental Health Survey (KoNEHS 2012–2014). The data were divided according to gender. The frequency and proportion of each variable were determined by dividing participants into two groups based on the top 75th percentile concentration of urinary TCS . Odds ratios (ORs) were calculated using logistic regression analysis for the high TCS exposure and low TCS exposure groups.Overall, the proportion of participants using personal care products was higher in women than in men. There was a significantly higher proportion of participants in the high TCS exposure group with younger age, higher education and income levels and with more frequent use of fragrance products, hair care products, body cleansers, cosmetics, and antimicrobial agents. In both men and women, ORs tended to increase with increased frequency of use of hair care products, body cleansers, and cosmetics before and after adjustment.Our findings demonstrate that as the frequency of use of personal care products increases, urine TCS concentration increases. Because TCS is a well-known endocrine disruptor, further studies are needed and explore other health effects with exposure to TCS in general population in Korea.The online version of this article (10.1186/s40557-019-0283-y) contains supplementary material, which is available to authorized users. Triclosan (TCS), chemical name 5-chloro-2-phenol, is a synthetic antimicrobial and antifungal agent, which is widely used throughout the world. TCS is used mainly as a disinfectant in soaps, detergents, toothpaste, mouthwash, fabrics, deodorant, shampoo, and plastic additives, and it is used in many personal care products, animal products, and industry and household products .TCS is absorbed into the body through the mouth and skin . TCS is TCS is known to be an endocrine disruptor that is structurally similar to polychlorinated biphenyls, bisphenol A, dioxins, and thyroid hormones . TCS incBecause of these health problems, various regulations have recently been established in relation to TCS in many countries. Various studies on TCS exposure levels have also been carried out. However, studies on TCS levels in Korea and related factors have not yet been conducted. In this study, we used a nationally representative data for the general population in Korea to analyze the level of TCS exposure in the general population according to the frequency of use of personal care products, which are the main exposure source of TCS.This study was based on data of the Second Korean National Environmental Health Survey (KoNEHS 2012–2014). According to Article 14 of the Environmental Health Act, the KoNEHS is conducted every 3 years to investigate the human exposure levels of harmful environmental factors in the Korean population, explore the influencing factors, and continuously investigate the spatial and temporal distribution and change in these factors .The survey area consisted of 16 cities and provinces nationwide. For the survey sample, the enumeration districts of the National Population and Housing Census 2010 were used for the sample population with the initial stratification classified by local administration. Secondary stratification was according to socioeconomic factors, using stratified multistage cluster sampling applied with proportional allocation of the square root of the population to extract 400 sample enumeration districts .In this study, after excluding 190 participants with missing urinary TCS concentration data, 6288 participants  were included from among a total of 6478 participants.To determine the association between TCS exposure and frequency of personal care products use, the frequency of use was classified as used rarely, less than once a week, and more than once a week. Personal care products were classified as hair care products, body cleansers, make-up products, nail care products, antibacterial agents, and fragrance products. Hair care products referred to products such as waxes, gels, and sprays. Body cleansers included foam cleansers, body wash, and shampoo, but not soap. Make-up products included cosmetic products other than basic cosmetics, such as skin care products and lotions; sun block products were also included. Antimicrobial agents refer to liquid-type antibacterial or sterilizing products .Sociodemographic variables and health behavior-related variables of participants were analyzed as follows. Age and body mass index (BMI) were averaged as sociodemographic variables. Education level was classified as below a middle school graduate level, high school graduate level, or college graduate and above. Marital status was classified as unmarried, married, or other , and socioeconomic status was classified into quartiles according to household income. Participants were classified as never, former or current smokers and alcohol drinkers. Participants were also categorized according to physical activity level as regularly performing no exercise, moderate exercise, or vigorous exercise.Urinary TCS concentration was measured using ultra performance liquid chromatography – tandem mass spectrometry (UPLC–MS/MS) with the Xevo TQ-S  using a spot urine sample . After hp < 0.05.The frequency and proportion of each variable were presented after stratification by gender to determine the general characteristics of participants. First, participants were divided into a high TCS exposure group and low TCS exposure group, based on the top 75th percentile concentration of urinary TCS . The frequency and proportion of each variable were then determined by gender. Chi-square tests were performed to analyze the difference in the distribution of each variable. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression for the high TCS exposure and low TCS exposure groups. Unadjusted models are presented and a multivariate adjusted model was adjusted for age, BMI, socioeconomic variables, and health behavior-related variables. IBM SPSS version 19 for Windows  was used for statistical analysis and the statistical significance level was set at The distribution of the independent variables in the present study was as follows Table . A totalUrine TCS concentration was determined according to high and low TCS exposure groups, based on the upper 75th percentile concentration; the distribution of independent variables is presented in Table Logistic regression analysis was applied to determine the degree of association between the frequency of personal care products use and urinary TCS concentration according to low TCS and high TCS exposure groups Table . In the In this study, general characteristics for high urinary TCS concentration were younger age, higher educational level, higher household income level, drinkers, and vigorous exercise group. In a previous study in Canada, higher urinary TCS concentrations were found among women with higher education and income levels, with higher TCS exposure levels in those over 25 years of age than in those under age 25 years . In the According to analysis of the relationship between the frequency of use of personal care products and urinary TCS concentration, we found that the frequency of use of hair care products, body cleansers, and cosmetics were consistently related to urinary TCS concentration in both men and women. In the upper 75th percentile of urinary TCS concentration, the proportion of more frequent products use was higher than among participants with rarely products use and ORs were higher in participants who used these products more often. Similar results were found in a study of breastfeeding mothers in Sweden. Mothers who used personal care products containing TCS showed significantly higher breast milk and plasma TCS concentrations than those who did not use these products . In addiAs a result of analyzing a list of the raw materials of cosmetics reported to the Korea Food & Drug Administration (KFDA) by domestic manufacturers in 2015, 127 of the 100,190 (0.13%) cosmetics products manufactured in Korea were found to have used TCS . It has According to the results of previous studies both on TCS toxicity in humans and use of personal care products as the main exposure source of TCS, regulations on the use of TCS for personal care products have been established in many countries. In Korea, KFDA launched a new regulation with TCS concentration in personal care products, such as, body cleansing products that are rinsed off after use, deodorants (excluding spray products), face powder, and foundation like concealer, that the concentration limit of TCS in personal care products was 0.3%; moreover, TCS could not be used in toothpaste and mouthwash in 2015 . In EuroIn the present study, similar to those of other countries, we found a tendency for urinary TCS concentration to increase in younger age, higher income level and education level. The present study findings also confirmed that personal care products represent the main cause of TCS exposure. People with higher levels of income and education tend to have greater interest in personal hygiene and tend to purchase personal care products, which may lead to increased exposure to chemicals such as TCS. Likewise, young people in their 20s and 30s are more concerned about personal care than children, adolescents, and elderly adults; therefore, this young population is more exposed to TCS through greater use of personal care products. TCS in women of childbearing age can be a potential neurotoxic agent for the fetus during pregnancy  and can The limitations of this study are as follows. First, we did not identify the usage amount of personal care products, only the frequency of use. Second, we did not consider the simultaneous use of other personal care products, use of other personal care products not included in the survey, and other TCS exposure factors apart from personal care products. Third, in about 60% of participants, urinary TCS concentration was measured below the detection limit. However, it did not affect the statistical analysis of this study. Fourth, the health effects of increased urinary TCS concentration were not analyzed. Despite these limitations, this study suggested the exposure level of TCS and the relationship with use of personal care products, which are major exposure sources of TCS using a representative data in Korean population.Regulation of TCS was initiated in Korea in 2015 and it is expected that the effect of reduction of TCS exposure by the regulation will be confirmed through the analysis of third KoNEHS data, which was conducted in 2015–2017 and not publically released yet. Furthermore, children over three years old were included in the study population in the third KoNEHS, therefore, the TCS exposure level and health effects could be studied in the susceptible population. Based on future studies, it could confirm the effect of the regulation and suggest another more powerful policy to minimize TCS exposure in Korean population.This study found out the association of the use of personal care products and the concentration of urinary TCS in general population in Korea. According to this study, the levels of urinary TCS were higher in female, younger people, and higher-income people. Because TCS is a well-known endocrine disruptor and several health problems related with exposure to TCS have suggested, further studies are needed to monitor the trend of urinary TCS level and explore other health effects with exposure to TCS in general population in Korea using a representative data for general population.Additional file 1:Medians (interquartile range) of Urinary TCS concentration according to age. The urinary TCS concentration tended to decrease as age increased. (XLSX 11 kb)


Predicting impact of plant tissue culture media components on explant proliferation is important especially in commercial scale for optimizing efficient culture media. Previous studies have focused on predicting the impact of media components on explant growth via conventional multi-layer perceptron neural networks (MLPNN) and Multiple Linear Regression (MLR) methods. So, there is an opportunity to find more efficient algorithms such as Radial Basis Function Neural Network (RBFNN) and Gene Expression Programming (GEP). Here, a novel algorithm, i.e. GEP which has not been previously applied in plant tissue culture researches was compared to RBFNN and MLR for the first time. Pear rootstocks (Pyrodwarf and OHF) were used as case studies on predicting the effect of minerals and some hormones in the culture medium on proliferation indices.Generally, RBFNN and GEP showed extremely higher performance accuracy than the MLR. Moreover, GEP models as the most accurate models were optimized using genetic algorithm (GA). The improvement was mainly due to the RBFNN and GEP strong estimation capability and their superior tolerance to experimental noises or improbability.GEP as the most robust and accurate prospecting procedure to achieve the highest proliferation quality and quantity has also the benefit of being easy to use. Pyrus communis were used. Pyrodwarf a hybrid of “Old Home” and “Gute Luise” is particularly tolerant to winter cold temperatures, calcareous soils and has a highly significant compatibility with all pear varieties. Moreover, it is characterized by a high precocity, good productivity, and producing uniform in size fruits with pear cultivars [Graft incompatibility and fruit quality are the present and future challenges that pear orchards are facing with them , 2. In tultivars . OHF as ultivars , 5. Therultivars . Microprultivars , hyperhyultivars –10, fascultivars  and hookultivars , while sultivars .3− (52 to 60 mM), low to moderate NH4+ (data not shown) and high mesos concentrations (1.5 × MS) for the best growth results. Another approach for optimization of MS medium was performed by [According to the previous studies,  (MS) is ormed by  who suggDue to various nutrition necessities of different plant species, it is difficult to obtain an optimized culture medium. Therefore, it is important to employ a trustworthy modeling system to achieve the highest growth performance .Biological systems are difficult to understand and model, largely due to the complexities of their system and non-linear nature; moreover, their dynamic characteristics are poorly understood. Usually, it is difficult to clarify biological interactions by traditional models and algorithms, particularly in the complex and noisy data set. Additionally, many studies have demonstrated that plant biology needs more attempts to find developing platforms for combining multidimensional data in order to draw biological interactions.In recent decades, several meta-modeling techniques have been emerged as promising methods for modeling high dimensional and non-linear processes. Artificial neural networks (ANN) , 23, genThe capability to quickly and effectively emulate nonlinear trends in data operation have helped setting up AI technology as a reliable meta-modeling platform for surrogate modeling in a wide variety of practical assignment, including science and engineering, because of their ability to utilize learning algorithm and detect input–output relationships in intricate, nonlinear processes. Among the numerous aspects of the AI paradigms, ANN technique has a wide range of applications in the field of plant biology and prediction of bioprocess quantitative properties. Successful applications of this approach have been reported in many studies. Among others, ANN was found as a promising technique to assess the effects of mineral nutrients on plant growth and productivity . ANN andRadial basis function neural network (RBFNN) is one of the most popular feed-forward ANN architectures in the literature for forecasting problems, among which the back-propagation (BP) algorithm is the most extensively used, and is a supervised learning model. The RBFNN can be considered as a special three-layer feed forward network which has certain advantages including better approximation capabilities, fast learning algorithms, simple network structures, and will not encounter the local minima problems , 34. RBFAlthough the reported approaches are fitting for modeling culture media, no approaches have been reported to provide effective and clear modeling results as well as explicit formulations of the studied phenomenon without presuming previous shape of the relationship , 40. ThiThe researches mentioned above exhibit the potential of AI methodologies as appropriate modeling tools for plant tissue culture. However, the literature survey revealed that no investigation has been done to use GEP for predicting new culture medium. This gave new impetus to the present study.Investigating the application of the GEP and RBFNN for modeling the effects of macronutrients and hormones on in vitro culture of Pyrodwarf and OHF rootstocks.Development of GEP-GA models in order to evaluate how Pyrodwarf and OHF microshoots respond to the mineral medium based on the number and length of new formed shoots obtained from the design of Box-behnken.Finding the optimal culture medium composition for maximizing the proliferation rate (PR), the average shoot length (SL), the quality index (QI), and minimizing shoot tip necrosis (STN) and vitrification (Vitri) by optimizing the obtained model using GA.The purpose of this paper is to apply two soft computing techniques namely RBFNN and GEP and to compare their prediction accuracy to Multiple Linear Regression (MLR) method as well as using GA algorithm aiming to predict and optimize pear culture media. The main contributions of this paper are as follows:This section evaluates the performances of the proposed models by analyzing the accuracy of each modelling approach for predicting the plant tissue culture media composition to studied fruit tree rootstocks micropropagation. Then GA-optimization of the most accurate modeling approach results is evaluated to achieve the most appropriate media compositions for each studied parameter. A framework of the performed experiments to achieve the best model is presented in Fig. 2, RMSE, MARE and MBE statistics of each developed model are given in Table The models were developed using MLR, RBFNN and GEP methods considering the media components variables that mainly affect the explant proliferation parameters. The MLR predictive model could not explain high variability of growth parameters due to the interaction of the variables considered, which may cover the media components effects. The mathematical equations obtained from GEP method that best approximate the growth parameters are given in Table 2 for GEP and RBFNN vs. MLR models were: PR = 0.992 and 0.957 vs. 0.583, SL = 0.974 and 0.990 vs. 0.904, STN = 0.961and 0.882 vs. 0.674, Vitri = 0.969 and 0.883 vs. 0.511 and QI = 0.943 and 0.891 vs. 0.668 in OHF and PR = 0.994 and 0.908 vs. 0.315, SL = 0.978 and 0.924 vs. 0.357, STN = 0.954 and 0.906 vs. 0.855, Vitri = 0.936 and 0.901 vs. 0.909 and QI = 0.944 and 0.923 vs. 0.902 in Pyrodwarf, respectively  corresponding to the GEP and RBFNN showed a substantially higher accuracy of prediction than for MLR models. As, the amounts of calculated R2 = 0.974 and 0.990, RMSE = 0.14 and 0.22, MARE = 0.034 and 0.058 and MBE = 0.012 and 0.040 for RBFNN and GEP, respectively). Therefore, to find the optimized medium for achieving the highest quality and quantity in proliferation, we optimized constructed GEP models using GA technique.Comparing the accuracy results of GEP and RBFNN Table  showed t4NO3, KNO3, mesos nutrients, micro-nutrients and 6-benzylaminopurine (BA) and indole-3-butyric acid (IBA) hormones to be used in the culture medium for achieving the maximum PR, SL and QI, as well as the minimum STN and Vitri occurrence in Pyrus rootstocks. The predicted values and the optimization of studied growth parameters by the GEP models are presented in Table Finally, the GEP models were analyzed to find the optimum levels of NH4NO3, 1.19 KNO3, 1.75 mesos nutrients, 3.28 micro-nutrients, 2.08 BA and 0.13 IBA could lead to optimal PR in Pyrodwarf (13.0) and media containing 2.00 NH4NO3, 1.19 KNO3, 0.62 mesos nutrients, 2.13 micro-nutrients, 1.59 BA and 0.17 IBA resulted in optimal PR in OHF (9.4). The optimal SL in pyrodwarf (5.0 cm) could be obtained with media comprising 1.83 NH4NO3, 0.51 KNO3, 1.74 mesos nutrients, 2.60 micro-nutrients, 0.60 BA and 0.16 IBA and in OHF (5.0) with media containing 0.90 NH4NO3, 1.35 KNO3, 2.04 mesos nutrients, 3.45 micro-nutrients, 1.81 BA and 0.10 IBA. Results of our study exhibited that media containing 0.93 NH4NO3, 0.50 KNO3, 2.30 mesos nutrients, 0.64 micro-nutrients, 0.51 BA and 0.07 IBA and 1.08 NH4NO3, 0.51 KNO3, 1.58 mesos nutrients, 2.36 micro-nutrients, 1.93 BA and 0.15 IBA could lead to minimum STN in pyrodwarf (0.00) and OHF (0.02), respectively. In Pyrodwarf rootstock (4.0), media with 0.50 NH4NO3, 0.50 KNO3, 2.50 mesos nutrients, 2.76 micro-nutrients, 0.50 BA and 0.05 IBA could result in the optimal point for Vitri, whereas in OHF rootstock (0.02) the optimal point for Vitri could be achieved with media supplemented with 0.50 NH4NO3, 1.27 KNO3, 1.49 mesos nutrients, 1.52 micro-nutrients, 1.31 BA and 0.14 IBA. Lastly, the optimization results of RBFNN models revealed that media containing 0.89 NH4NO3, 0.50 KNO3, 2.50 mesos nutrients, 4.0 micro-nutrients, 0.50 BA and 0.05 IBA in Pyrodwarf (4.99) and 0.99 NH4NO3, 0.53 KNO3, 1.88 mesos nutrients, 2.12 micro-nutrients, 2.59 BA and 0.18 IBA in OHF could produce optimal explant quality.Comparing observed and predicted outputs showed the behavior of the constructed models from investigating inputs. The GA optimization analysis on the GEP model showed that media containing 1.56 NH4NO3, KNO3 and micro-nutrients and BA and IBA hormones and increase in mesos nutrients may reduce PR but it also may reduce STN and Vitri occurrences which cause the higher QI of in vitro multiplied Pyrodwarf rootstock. But it was a little different for OHF rootstock as decrease in NH4NO3 and KNO3 and increase in mesos nutrients and BA hormone caused lower STN and higher QI, but decrease in KNO3 was not effective on Vitri reduction. The positive effect of reduction in NO3− and NH4+ concentrations on PR has also been previously reported [2 has also been stated b by [The media components suggested by the optimized GEP model revealed that although decrease in NHreported  on G × Nted b by .Actinidia deliciosa) [AI has recently been successfully and progressively applied in plant bio-researches  as well liciosa)  and the liciosa)  are someliciosa) . The menliciosa) .Pyrus rootstocks.In the present study, we used RBFNN as a more robust predicting tool than MLPNN due to working as an interpolator in multidimensional space whereas MLPNN works in stochastic manner. In the other words, RBFNN is more ‘function approximator’ than ‘pattern recognizer’ whilst MLPNN is the contrary . GEP alsThe main advantage of ANN-based models is that they do not require a preceding specification of appropriate fitting function so; they have a general approximation capability to estimate practically all types of non-linear functions. This flexibility characteristic may benefit the modeler to construct a model with the highest probable prediction accuracy.One of the most important advantages of using GP-based methods like GEP, over other approaches is their ability for production of prediction equations without any assumption for prior form of the relationship. GP as well as its variants have been employed by many researchers to discover any complex relationships which fit various experimental data –55. A poPyrus rootstocks showed that the performance of explant in response to macronutrients concentrations varies according to the pear rootstock genotype, as well. So that, NO3− was found to be critical for OHF explant while NH4+ was found to be critical nutrient for Pyrodwarf explant growth and therefore, we suggested that the use of ANN-based model analyses would lead us to detect the optimized macronutrient concentrations essential to maximize the PR and SL and minimize the occurrence of STN and Vitri [Pyrus genotypes because of the incidence of the physiological disorders like hyperhydricity and necrosis at the explant multiplication stage. In order to design an optimized culture medium, use of a trustworthy mathematical modeling and optimization technique is necessary to achieve an optimal and efficient growth [Our previous results on the same nd Vitri . Due to nd Vitri . Moreovet growth , 50, 51.t growth . RSM andt growth , 19. Thet growth , 58. It t growth , 59.Pyrus rootstocks to nutrients and hormones concentrations. These optimized models could reveal the importance of each studied nutrient or hormone in increasing or decreasing each studied feature. Previous studies using ANN-GA models on G × N15 Prunus rootstock from a gathered data proposed that the role of NH4+, NO3−, PO42−, Ca2+, and K+ were more important than SO42−, Mg2+, and Cl− in in vitro proliferation [Briefly, we found different RBFNN-based models with optimization algorithm to integrate the obtained data set of the in vitro responses of 4NO3 and KNO3 are the major sources of nitrogen and potassium for Pyrus rootstocks micropropagation. The importance of the ratio between NO3− and NH4+ concentrations has been widely discussed in literatures [4+ concentration and optimizing NO3− concentration, simultaneously. But they predicted that enhancing the NH4+ concentration will increase SL while producing non-healthy shoots while reducing its amount will increase the quality of plantlets. It has been suggested that an optimized culture medium would produce a higher number and length of shoots. Andreu and Marín [NHeratures –63. The eratures , 64, 65.eratures . Comparieratures , 50, 51 eratures  predictend Marín  reportednd Marín , 67, 68.nd Marín , 50, 51 nd Marín , 50, 51 Prunus rootstock showed that using cytokinin and auxin together in the medium will make higher shooting than using each alone. They indicated that the concentration and interaction of hormones are two important factors on in vitro shooting. In accordance with these results and the findings of [Interactions between plant hormones make a critical complexity in regulating plant growth processes. Cytokinin has been shown that regulates cell proliferation  and auxidings of , 72, we dings of . The advdings of  was repodings of  with hordings of , we consIn general, the use of ANN-based models such as RBFNN leads to the high accuracy of estimation whereas GEP models are easier in the use to give it an explicit mathematical equation in prediction of explant growth parameters as well as being more accurate than RBFNN method. No studies have been done on the superiority of RBFNN or GEP approaches for estimating in vitro explant proliferation parameters with optimal use of media components. Therefore, according to the current results, the approaches presented here would allow more accurate estimations without the need for the availability of all data.The main objective of this paper was to compare the performance of MLR, RBFNN and GEP models for predicting the concentrations of in vitro medium components to achieve the optimal growth parameters. Different combinations of the nutrients and hormones were used as inputs for the MLR, RBFNN and GEP techniques. The proliferation parameters were estimated from the GEP equations. PR, SL, Vitri, STN and QI were chosen as the main indices of proliferation state. Our results suggested that using RBFNN and GEP techniques leads to more accurate results. The optimized GEP models gave us the most appropriate formulation for each studied parameter so, these results can cause finding the most efficient protocol. The GEP constructed models were the most accurate models as well as being easier to apply, as they estimate growth parameters using explicit statistical equations. Using further optimization techniques are suggested for future studies on predicting and optimizing plant tissue culture media by GEP modeling procedure to achieve the most appropriate results.MLR, RBFNN and GEP modeling procedures were used to construct models by using different combinations of minerals and hormones concentrations as inputs and various measured proliferation parameters as outputs. The GEP models were applied to find the optimized models using GA. Two case studies were performed using two pear rootstocks which have described details of the used techniques to realize the optimized inputs compositions as follows.−2 s−1 (121 °C) for 15 min. All cultures were incubated at 25 ± 2 °C with a 16-h light period (80 µmol m2 s−1) of white fluorescent light for 4 weeks. Afterwards, variables including PR, SL, Vit, STN and QI were recorded. In each set of experiments, each treatment consisted of 10 replicates (jam jars) and each replication included four explants for both Pyrodwarf and OHF rootstocks.Pear rootstocks Pyrodwarf (“Old Home” × “Gute Luise”) and OHF (“OldHome” × “Farmingdel”) from in vitro cultures were grown in modified macro- and micro-nutrient MS media supplemented with 30 g/l sucrose, 8 g/l agar (DuchefaH) and different concentrations of cytokinin and auxin hormones. Media pH was adjusted to 5.7, distributed into 250 ml jam jars with polyethylene caps and autoclaved at 1 kg cmIn recent years, multivariate experimental designs such as Central Composition and Box–Behnken designs (BBD) have been frequently used for evaluating the effects of variables in many processes. The most important advantage of these designs is decrease in the number of experiments essential to conduct the studies, which results in saving time and cost as well as a decrease in materials and reagents consumption. Additionally, the statistical analysis carried out on the results is quickly realized and the percentage amount of experimental error is diminished –79. In t3, NH4NO3, Mesos, minors, BAP and IBA were determined as independent (input) variables and PR, SL, Vit, STN and QI were selected as dependent (target) variables. Different concentrations of independent variables were determined based on their content in MS medium (1 × MS concentration) , 0 (mid) and + 1 (high) Table , the expAt least 10 replicates were used for each experimental run. 357 experimental sets  were randomly selected among 510 sets in order to train the modeling procedures and the other 153 sets  were used to test the models generalization capacity.MLR analysis is considered as a multivariate statistical technique to analyze the relationship between a dependent single variable and a group of independent variables. Prediction and explanation are two main objectives of MLR. The prediction of MLR involves the extent to which the dependent variables can be predicted by the independent variables. The explanation of MLR evaluates the regression coefficients, their sign, statistical interface and magnitude, for each independent variable .Linear regression is characterized as the oldest statistical technique in regression and it is thought to be a benchmark method to be employed by new techniques. Like other regression techniques, MLR models the relationships between two or more independent variables and a response variable; this is accomplished a linear equation fitted to the observed data. In this approach, every value assigned to the independent variable k is associated with a value assigned to the dependent variable M. The regression line of population for n input variables × 1, × 2, …, kn is as follows:M is the dependent variable, α0 denotes a constant named intercept, k =  represents an input variables vector and α denotes the regression coefficients vector, each of which belongs for each explanatory variable. The observed values of Y have different means and are assumed with the equal standard deviation ε. The software package of SPSS 19 was utilized in the MLR model.The RBFNN is able to simulate the brain of human to accomplish several different tasks easily. It can also crystallize the complex relation between the inputs and outputs using a fitting process which leads it to an approximation of any nonlinear function , 86, 87.j; The RBFNN is comprised of three different layers: an input layer, a hidden layer and an output layer. The input–output relationship of this RBFNN network can be described by:d method , 89 was GP is also utilized to model the behavior of structural engineering problems. It is a genetic algorithm extension which uses a program space for search, instead of employing a data space. One of the most important advantages of using GP-based methods over other approaches is their ability for production of prediction equations without any assumption for prior form of the relationship. GP as well as its variants have been employed by many researchers to discover any complex relationships which fit various experimental data , 25, 42 GEP is rooted from evolutionary algorithms like GP and GA. A population of individuals is used in this method and then, better individuals are selected by employing genetic variations and fitness function. Genetic operators introduce the genetic variations. GEP as a learning machine, is supposed to learn the relationship between variables in groups of data. The difference between GEP and its precursors GP and GA is in the way of individual programming as in GEP, individuals are programmed as fixed length linear strings (chromosomes) which are shown eventually by expression trees which are a simple diagram presentation. However, individuals are expressed in GP and GA as fixed length linear strings (chromosomes) and nonlinear entities of different shapes (parse trees) and sizes, respectively. Genetic operators work at the chromosome level in GEP making creation of genetic diversity very simple, which is considered as one of its strengths over GP and GA. The unique, multi-genic nature of GEP is its other significant point allowing more complex programs with several sub-programs to be evolved. The benefits of both GP and GA are combined in GEP, while some of their limitations are met , 45, 92.In GEP the individuals are encoded as fixed size linear strings (chromosome), which are then shown as non-linear entities with different shapes and sizes, known as Expression Trees. For example, the expression of Eq.  can alsoThe actual phenotype of GEP chromosome is this representation and the genotype can be easily explained from the phenotype as shown in Eq. 5\documenAs we read a page of text, the genotype is characterized as the straightforward reading of the expression tree from left to right and from top to bottom. The Eq. , for exaThe GEP functional steps are shown in Fig. GEP system uses roulette wheel sampling with elitism to select and copy the individuals into the next generation based on the fitness. This guarantees that the best individuals are survived and cloned to the next generation. When single or several genetic operators are conducted on selected chromosomes, including rotation, mutation and cross over, variation is introduced in the population.The software package of GeneXpro was employed to run the GEP models. All parameters used in the GEP models are shown in Table The mathematical operators and functions chosen in the present study are illustrative and not conclusive as the plant modeling designer as the freedom to choose such functions so as suit the anatomy of the problem under study. The operators and functions were chosen with a perspective of invoking simplicity of the evolved model promising faster convergence. The population size (number of chromosomes) sets the number of programs in the population. Larger population size takes longer for an iteration run. A large number of chromosomes were tested to find models with minimum error. The program was run until there was no significant improvement in the performance of the models. The present study was undertaken to attain explicit relationship between response variables and decision variables. GEP explicit formulations for PR, SL, STN, Vit and QI were obtained as a function of experimental parameters as follows:3, NH4NO3, Mesos, Micro, BA and IBA).PR, SL, STN, Vit and QI = f  were used with the following formulas:Oi and Pi are observed and predicted amounts, respectively; and In order to evaluate and compare the precision of different models, four statistical indices including root mean squared error (RMSE), mean absolute relative error (MARE), mean bias error (MBE) and correlation coefficient (R


The following results were obtained. First, there was significant difference in RMR between sexes when body-weight effects were factored out. Second, significant local variation in RMR was detected by analyses of both variance and covariance, with one population showing significantly reduced RMR and another significantly increased RMR. Third, regression analysis indicated that the local mean temperature and mean annual days of rainfall were the two significant factors associated with the aforementioned inter-population difference in RMR. The implication of such an association was discussed.Scorpions are well known for their reduced resting metabolic rate (RMR) in comparison to typical arthropods. Since RMR is a key physiological trait linked with evolutionary fitness, it is expected that there may exist intraspecific RMR variation given the ecological and geographical heterogeneities across the distributional range of a species. Nevertheless, it is unclear whether RMR variation exists among scorpion populations. Here, we compared the RMR (VCO Summary: Metabolic rate variation is observed between the two sexes and among populations in the Chinese scorpion, with the latter being correlated negatively with local mean temperature and positively with annual days of rainfall. Scorpio maurus palmatus (Scorpiones: Scorpionidae) and the surface-dwelling Leiurus quinquestriatus (Scorpiones: Buthidae) , posits that RMR variation is primarily a consequence of an organism's body weight and temperature differences (Scorpions are well known for their low resting metabolic rate (RMR) . Lightonuthidae) . Among tferences , whereasferences . Howeverferences .Smeringurus mesaensis (Scorpiones: Vaejovidae)  .Second, the widespread occurrence of ecological and geographical heterogeneities over the distributional range of a species constitutes another potential source of RMR variation, since this would promote local adaptation  . Indeed Mesobuthus martensii as a study model to investigate (i) whether there exists a difference in RMR between sexes, that is, do scorpions follow the general pattern of RMR being higher in males than in females? And (ii) whether intraspecific RMR variation exists among populations, and if it does, whether any ecological factors are associated with it. M. martensii belongs to the family Buthidae of the arachnid order Scorpiones, and is endemic in East Asia  in the eastern region of China across an area of about 0.4 million km2. RMR was measured under identical experimental conditions and the possible effects of weight, sex, along with local environmental factors  were examined.Here we used the Chinese scorpion ast Asia , 2015. Eears ago . M. martcapacity  associatcapacity . This stM. martensii individuals from 21 localities (groups) (2 h–1 (mean=45.5510). All data were pooled together and each individual was regarded as a data point. By plotting log10RMR against log10Weight (10RMR=(0.8362±0.055)×log10Weight+(1.6926±0.01) , which can be re-transformed to:2 h−1, Weight in g and parameters were expressed in mean±standard errors of the mean (s.e.m.). Hence, the allometric exponent b was 0.8362 for M. martensii. The mass-corrected RMR was estimated based on the parameter b  and used for the subsequent analysis of variance (ANOVA).A total of 189 (groups) , Table 110Weight , the estN=84) and females (N=105) showed slight difference  (with weight effects factored out), male RMR was about 42.93 versus 41.04 μl CO2 h−1 in females. The significance of sex-based difference in RMR was rejected by ANOVA (P=0.157) but supported by ANCOVA (P=0.00525)  .Table 2post-hoc P<0.05) (post-hoc P<0.05)  found no significant RMR difference between any two populations, whereas that of a similar ANOVA (data not shown) revealed only two significant pairwise differences, that is BJYQ (No. 1) versus SDZC (No. 14), and BJYQ versus AHBZ (No. 19).Multiple pairwise comparisons following the two-way ANCOVA and two-way ANOVA  revealed P<0.05) A, wherea P<0.05) A. When pP<0.02) deviated from the normal distribution. Moreover, using non-averaged values, the two-sample t-test also showed markedly reduced mass-corrected RMR in population LCGX versus all individuals pooled together (P=5.67e–05), and increased mass-corrected RMR in SDDY versus all individuals pooled together (P=1.34e–03).We further compared the mean RMR of population LCGX (SDDY) with that of all studied populations. Based on both mass-corrected RMR and adjusted RMR by ANCOVA (hereafter termed collectively as weight-independent RMR), the LCGX and SDDY samples were the two extreme data points, with relatively low RMR in population LCGX and high RMR in SDDY B. Two apM. martensii. The following linear relationship was obtained :2 g−0.8362 h−1, Temperature in °C, Altitude in m, and the intercept P=1.12e–05  correlated with the variation in RMRs  instead of group-specific coefficients for each group  adopted. That is, when the exponent was arbitrarily given as 1 (i.e. b=1) such as in P-value of 0.03 (data not shown). By contrast, when accounting for the mass differences with b=0.8362, the corresponding P-value was 0.157  in M. martensii. This was in accordance with previous finding in the arid zone scorpion Urodacus yaschenkoi (Scorpiones: Scorpionidae)  is the masking effect of the treatment temperature. It is noteworthy that sexual dimorphism in mass-specific RMR was common in many invertebrates. For example, Phoracantha recurva and Phoracanthasemipunctata; Aphonopelma anax; 2 production associated with sexual dimorphism in the thynnine wasp Zaspilothynnus nigripes.With body weight as covariate, ANCOVA has been regarded as a superior approach to ANOVA . Our ANCionidae) , but incesaensis . It has M. martensii.It is believed that RMR variation between sexes is mainly due to the male and female's different lifestyles see , and hig2 in the eastern region of China (Our results of both ANOVA and ANCOVA demonstrate that RMR variation existed among the Chinese scorpion populations. This adds scorpions to the list of arthropods that exhibit population-level metabolic rate difference such as the springtail (six populations) , the Colof China . We assuof China , Fig. 4Aof China , Fig. 4Bof China . The RMRof China  and 3, aof China .M. martensii, great geographic and ecological heterogeneity exists, which can create diverse local environments, which in turn may lead to differential adaptation among different scorpion populations (M. martensii populations (unpublished data). This would provide a genetic basis for complex phenotypic plasticity as well as potential local adaptation, both of which can lead to the metabolic rate variation observed here. Given the current debates on the role of evolution on RMR variation, the observations reported here in M. martensii clearly deserve a further in-depth study.The significant association of RMR with environmental factors observed here signals some kind of metabolic response to the local climate, as a result of either adaptation or more immediate acclimatization, although our experimental design in the present study does not permit to make the discrimination. It is worth noting that differences in temperature response between populations from different locations have frequently been found to be the result of genetic differences rather than being attributable solely to acclimatization . Actuallulations . Ongoingulations  and the M. martensii, between sexes and among populations. Local mean temperature is significantly negatively correlated with population-level RMR, while the mean annual days of rainfall positively correlated with population-level RMR. The significant association of population-level RMR with local environment is likely to reflect the scorpions' metabolic response to local climate, either as a result of adaptation or acclimatization.We demonstrate that intraspecific RMR variation exists in the Chinese scorpion M. martensii samples were collected during July and September 2015, from 21 geographic localities (populations) from seven provinces covering an area of roughly 0.4 million km2 in the eastern region of China  at 25±2°C, relative humidity 50±10% and a natural photoperiod. Measurements began after an acclimation period of at least 7 days in incubator, during which mealworms were given to the scorpions twice a week. Laboratory acclimation helped to minimize within-individual RMR variation of field-collected scorpions through the experiment period, hence maximizing the repeatability of RMR measurement and reducing noises in between-individual/population differences , Chinese Academy of Sciences (CAS). The of China , Table 1ferences .2 production was determined using an open flow-through respirometry . The outside air firstly passed through the Sub-Sampler Pump (SS-4), then into the Mass Flow Controller (MFC2), finally into the Carbon Dioxide Analyzer (CA-10A). Data were collected, analyzed using Universal Interface (UI-2) and ExpeData data acquisition software , which also controlled the eight-channel multiplexer. Data were recorded every 1 s. All measurements were conducted during the daytime, which was the resting phase of the nocturnal scorpions. Each individual was weighed to the nearest 0.01 g with an electronic balance  following the flow-through respirometry measurements.The CO2 fluctuations, an additional ∼30 l dry and empty plastic container was supplied in front of SS-4. We set the flow rate at 60 ml min–1. Four respirometry chambers attached to a multiplexer were placed in the incubator, with one acting as a baseline and the other three containing scorpion individuals. Glass chambers that had relatively small volume (∼10 ml) were used to reduce the possibility of the scorpions moving, which may have lead to a several-fold increase in CO2 production.In order to avoid air CO2 release in our experimental condition was continuous, which indicated a continuous pattern of gas exchange in M. martensii here; (ii) we have also extended the stationary phase to 10 min and similar result was obtained. Scorpion activity was determined when a sharp increase of CO2 release was detected at lag or stationary phase. For each experimental run, the initial 30 min were not recorded and the first one to two cycles were usually abandoned as well, because scorpion activity was sometimes detected during these times. Median value of the remaining eight to nine cycles was calculated as the final result for each individual.A complete experimental run lasted for 120 min, consisting of ten cycles (repeats). Each cycle lasted 12 min, with a 1.5-min baseline each at the start and end of the cycle, and three 3-min measurement periods of scorpion-containing chambers. The 3-min measurement period consisted of three phases : lag phahttp://data.cma.cn) and rp5.ru website. For a few collection sites where no climate records are available, data from the nearest weather stations were employed instead.Latitude and longitude were determined by a GPS receiver. Altitude information was then produced via importing position information into Google Earth (version 7.1.5.1557). Climate data, including the mean temperature (Temperature), mean relative humidity at a height of 2 m above the ground (RH), mean annual rainfall , and mean annual days of rainfall  from 2005 to 2015, were mainly obtained from the National Meteorological Information Center (P>0.07) for all analyses, except for the variance homogeneity  between males and females for ANCOVA. In such a situation, we followed To explore the RMR differences among populations, ANOVA and ANCOVA was conducted in R (version 3.1.3). The assumptions of data normality and homogeneity of variances were satisfied (2 h−1) tend to exhibit highly regular (power-law) relationship with body mass (in g)  as the dependent variable (in μl CO2 g−b h−1), while group (sample collection sites) and sex as two independent variables . We elected the simple model ‘group+sex’ for ANOVA, omitting interaction effects across predictors because of the interaction P>0.05 (see Results). The post-hoc analysis was based on Tukey's HSD test that used a correction of P for multiple testing.Animal RMRs (here in μl COs (in g) :(3)To prs method . The val10RMR being used as dependent variable (in μl CO2 h–1) whereas log10Weight as covariate (in g). Group (collection site) and sex were the two predictors. Homogeneity of regression slopes was confirmed by checking whether there were interactions between covariate and predictors (P>0.05 here). ANCOVA run with simple model, as described above. For the post-hoc analysis of ANCOVA, we used the glht function  in the package ‘multcomp’ to identify significant differences between the group means adjusted for contributions of body weight.A two-way ANCOVA was also performed, with logTo find the relationship between RMRs and local environment, a multiple linear regression was used. Regressors were selected via both an automatic method and all possible regressions approach; the former used the function stepAIC from package ‘MASS’, whereas the latter the function regsubset in the package ‘leaps’. These two algorithms yielded identical results with three out of seven factors being retained, and the best model was ‘(Mass-corrected RMR)∼Temperature+Rainfall-Days+Altitude’.


P = <0.001; R2 = 0.1279), while GAS  or Influenza infection  were not associated with failed OAE screening. Correlation between number of AOM infections and number of failed OAE screenings was not strengthened by presence of asthma. This study found evidence of an association between childhood history of AOM and failed OAE screenings in adolescence. Since this population may be at a higher risk for developing permanent or fluctuating hearing losses, further studies to clarify indications and timing of standard audiological testing among these children should be considered.This study aims to assess prospectively whether there is an association between frequencies of upper respiratory tract infections (URTI) or asthma in early childhood and failed otoacoustic emission (OAE) screenings later in life. There are no clear recommendations for hearing testing following acute otitis media (AOM) infection. This is a retrospective, practice based chart review. Participants from a primary care setting were 517 pre-adolescent and adolescent children  , who had presented with at least one specific bacterial URTI  tonsillitis, or Influenza) during childhood. Hearing testing was recorded incidentally at all subsequent routine health care maintenance visits (OAE hearing screen). Simple linear regression analyses were performed using R (v3.4.4). We found that number of episodes of AOM infections strongly correlated with number of failed OAE screenings later in life (F = 76.37;  Streptococcus pneumoniae, Haemophilus influenzae and others) or viral , rhinovirus, influenza, adenovirus, and others) [Upper respiratory tract infections (URTI) (acute otitis media (AOM), group A streptococcus (GAS), acute pharyngitis and tonsillitis) are common childhood conditions  that hav others) –6. Howevet al. studied long-term hearing outcomes and middle ear pathology in a 30-year follow-up in individuals with onset of recurrent AOM (rAOM) before the age of three [Krakau, of three . They reof three . Howeverof three . In contof three .Possible mechanisms by which AOM can cause direct hearing loss may include pathogens or inflammatory immune responses, which damage the middle ear –6. StrucStudies have shown that there is no long-term impact of otitis media with effusion (OME) on language development in children –10. HoweOAE testing is a helpful diagnostic tool which is gaining higher adoption rates in the primary care setting for objectively assessing hearing status . A stimuWhen considered among the middle school and high school aged population, a persistently obliterated OAE response assumed to be due to middle ear conditions may overshadow permanent noise-induced hearing changes. These changes are fully preventable and highly topical when considering health risks for this age bracket. Therefore, it is important to understand the long-term otological and audiological changes that may persist in the ears of children with strong early histories of various URTIs.In the current study, we compared the OAE outcomes in pre adolescent and adolescent children with AOM, GAS, or influenza infections and asthma using data from electronic medical records. This investigation addresses a gap in the literature, which is important for understanding URTIs in early childhood and their possible sequelae including hearing loss.We used data obtained from an electronic medical record (EMR) database from an outpatient pediatric private practice  between 2003–2018. For this retrospective chart study, all patients were older than 10 years at the time of this study, and had at least one lifetime episode of presumed bacterial URTI . Inclusion criteria also included serious viral URTI such as influenza A or B. The SUNY Downstate Medical Center Institutional Review Board approved this study without the need for written informed consent due to lack of patient identifiers.et al [Physician diagnosis of unilateral or bilateral AOM was based on symptomatology and determined by otoscopy as recommended by the American Academy of Pediatrics guidelines described in Leiberthal, et al . Symptomet al . PhysiciAudiological testing was administered using a Distortion Product Otoacoustic Emissions hearing screener , which was performed on all patients at routine health care maintenance visits. The frequency of OAE measurements was between 2000 and 5000 Hz. Abnormal hearing result was defined as absence of otoacoustic emissions at 2/6 frequencies between 1000 and 8000 Hz, with a pass/fail result recorded. Patients with a failed screen were ultimately referred to an audiologist for comprehensive evaluation.P values for differences in male and female patients (i.e. failed hearing screen). A two-sided P value of < 0.05 was considered statistically significant. All statistical analyses were performed in R using R-Studio (version 3.4.4).The association between AOM, GAS or influenza and failed hearing screenings later in life was modeled using binomial logistic regression and linear regression, with baseline characteristics at study entry. The effect of variable asthma status was determined by linear regression. Adjusted odds ratios are presented with 95% confidence intervals. Mann-Whitney U-tests were performed to calculate P = 0.16). Of the patients, we report asthma (4.1%), atopic dermatitis (AD) (15.3%) and both asthma and AD (1.5%) (D (1.5%) .P = <0.001; R2 = 0.1279)   (2 = 0.07785).In our total population, number of episodes of AOM infections strongly correlated with number of failed otoacoustic emission screenings later in life  , while n 0.0016)  or numbe 0.0031)  were notP = <0.0001; R2 = 0.5188)    , while n 0.0014) , or numb= 0.019)  infectioAge range of AOM infections is represented in In the present work, we examine URTIs in early life and sequelae later in life. This is illustrated by a significant association between numbers of AOM episodes in early-life and failed hearing screenings via OAE later in life. Interestingly, there was no independent effect of asthma status. Our study could not reveal significant differences in the numbers of GAS or Influenza infections and failed OAE screenings. The combination of these findings suggests that specifically AOM early in life may contribute to persistent abnormal hearing results in certain patients, even through adolescence. This underlines the importance of closer monitoring for relapse of temporary hearing loss or development of permanent hearing loss, in order to ensure accurate diagnosis and treatment in this at-risk population.AOM is characterized by otoscopic findings and mostly causes conductive hearing loss by damaging the middle ear . Our maiThe role of URTIs in the context of hearing loss has been theorized in the literature. AOM pathogenesis can involve interplay between virus, bacteria, and the host immune response . It has Other explanations by which AOM can directly cause hearing loss include that fact that subjects who have had more frequent AOM are more likely to have effusion at the time of the hearing tests . Current effusion would explain a degree of hearing loss. Lastly, rAOM is associated with an increased risk of chronic otitis media with effusion (COME). Both rAOM and COME are often treated with tympanostomy tube placement (TTP) . This suet al. demonstrated that history of OM in children aged 2 to 11 years was associated with history of asthma and wheezing [Prior literature has reported that repeated infections during childhood are linked to the development of asthma or atopic disease –18. Studwheezing . Howeverwheezing –22. Theswheezing , 23. Riswheezing ; howeverwheezing .The second important finding reported was that diagnosis of asthma did not have any significant effect on the association observed between numbers of AOM and failed hearing screens. Even though previous studies have demonstrated a positive association between asthma and recurrent ear infections in children –25, it iEven though the American Academy of Pediatrics (AAP) published recommendations for hearing screening beyond the newborn period, pediatricians have little guidance on screening and/or referral criteria past the infant stage –30. The This study has several limitations that need consideration. First, patients in this study diagnosed with AOM do not have a specific microbiologic diagnosis. Second, we do not report non-infectious disease related diagnoses, as these are not consistently documented for all patients in the study population. Third, the distortion-product OAE method used for hearing screening finely detects abnormalities of the auditory pathway which do not always translate into clinical hearing loss. It should also be mentioned that the lack of association between numbers of AOM, GAS, or Influenza infections and number of failed OAE screens in asthma may be due to the small sample size. However, our study has several strengths, including the inclusion of a pediatric cohort from a large single practice with excellent follow-up from birth to adulthood in the same children. This allows a complete chart review analysis in order to ascertain exact numbers of lifetime AOM and other respiratory infections based on clinician assessment and not patient recall, therefore, avoiding differential and non-differential recall bias.It should be stressed that middle ear pathology can obscure the presence or absence of a permanent hearing issue, which is why it is advisable to preventatively screen later in life once peak incidence of AOM has passed . There iAOM is a public health concern with significant financial burdens on the healthcare system –33. Our The data presented in this study show that there exists an association between AOM infections in children early in life and failed OAE screenings later in life. This finding has potential implications, in terms of understanding the relationship between AOM and subsequent permanent hearing loss, as well as developing new universal screening approaches to better identify individuals at risk for hearing management and audiological intervention. Since noise-induced hearing loss is a growing public health concern in the adolescent population, it is important that key clinical features arising from early history of OM do not mask new, preventable changes to hearing. Future studies should prospectively evaluate such public health approaches and the impact on hearing loss.


The burden of severe hearing impairment is increasing with two-thirds of these hearing impaired people residing in developing countries. Newborn hearing screening helps to identify early, babies who need intervention in order to prevent future disability. Neither universal nor targeted hearing screening programme is available in Nigeria.Objectives: This study was carried out to assess the prevalence of hearing impairment among high-risk newborns in UCH and the associated risk factors.Materials and Methods: Two hundred one newborns in the neonatal unit of UCH with risk factors for hearing impairment had hearing screening done using automated auditory brainstem response (AABR) at 30, 45, and 70 dB at admission and discharge, and those that failed screening at discharge were rescreened at 6 weeks post-discharge.Results: Eighty-three (41.3%) and 32 (15.9%) high-risk newborns failed at admission and discharge screening respectively, and 19 (9.5%) still failed at follow up screening. The majority of hearing loss at follow up was bilateral (94.7%) and severe (52.6%). The risk factors associated with persistent hearing loss at follow up were acute bilirubin encephalopathy , IVH , meningitis , recurrent apnoea , severe perinatal asphyxia NNE III .Conclusion: Severe and bilateral hearing impairment is a common complication among high risk newborns in UCH persisting till 6 weeks post-neonatal care. Severe perinatal asphyxia with NNE III, ABE, IVH, meningitis and administration of amikacin for more than 5 days were significant risk factors. We recommend that SCBU graduates with these risk factors should have mandatory audiologic evaluation at discharge. Intact hearing is an essential requirement for speech and language development, so children with hearing loss will be unable to develop speech and this puts such children at a disadvantage socially, emotionally, educationally, and economically among their peers , 2 HeariThe prevalence of hearing impairment has been on an astronomical increase especially in the last three decades. World Health Organisation (WHO) reported 42 million people affected globally in 1985, which has increased to 360 million people by the year 2012 –9. A retThe tests of auditory function recommended for use in newborns are the otoacoustic emmission tests (OAEs) and automated auditory brain stem response (AABR). These two methods provide non-invasive recordings of the physiologic activities of the auditory system and also require minimal patient cooperation. Both technologies are affected by fluids and debris in the auditory canal in the first few days of life. AABR reflects the integrity of the entire auditory pathway, while OAEs will only assess the peripheral auditory system . A sensiThe actual prevalence of hearing impairment in Nigeria is unknown but Olusanya, Wirz, and Luxon in a community-based infant hearing screening programme using a two-stage screening protocol (TOAE and AABR), reported an incidence of permanent hearing impairment (≥30 dB hearing level) among infants attending immunization clinics most of whom were born outside regular hospitals as 28 per 1,000 babies screened . This prMost children with hearing impairment in Nigeria are diagnosed only when speech has failed to develop, partly because of the absence of routine or targeted newborn hearing screening , 14 and This study set out to perform hearing screening in all neonates admitted into the neonatal unit of the University College hospital with risk factors for hearing impairment pre and post exposure to the risk factors. This was with a view to defining the prevalence of hearing impairment in high risk neonates and determine the associated risk factors.This was a longitudinal cohort study of babies with risk factors (JCIH risk factors)  for heart-test was used to compare the mean TSB of subjects with hearing impairment and those with normal hearing. Relative risk was calculated for each risk factor at 95% confidence interval. Logistic regression analysis was utilized for multivariate analysis to determine predictors of hearing and statistical significance was set at 5%.Data was entered and analyzed using SPSS version 20.0 software. Descriptive statistics such as means, standard deviations and medians (ranges) were used to report continuous variables while categorical variables were summarized by percentages. Pearson Chi-square test was utilized for bivariate analysis of dependent and independent categorical variables (risk factors associated with hearing impairment), while student The calculated minimum sample size required at 95% confidence interval was 200 subjects.Ethical approval for the study protocol was obtained from the University of Ibadan/ University College Hospital Joint Ethics Review Committee (UI/EC/13/0355).n = 106, 52.7%) while 95 (47.3%) were preterm. The mean ± SD weight on admission was 2350 ± 910 g , mean length was 45.0 ± 5.5 cm and mean occipito-frontal circumference was 32.1 ±3.4 cm. Birth weight was ≥ 2,500 g in 97 (48.3%), 1,500– < 2,500 g in 60 (29.9%) babies., 1,000– < 1,500 g in 36 (17.9%) babies and < 1,000 g in 8 (4%) babies. Five (2.5%) were large for gestational age (LGA) while 31 (15.4%) were small for gestational age (SGA) and the rest  were appropriate for gestational age (AGA).During the study period, 227 newborns were admitted into the neonatal unit, 216 were recruited into the study but only 201 (93%) completed the study as shown in Figure n = 95, 47.3%) were delivered in UCH, the rest were outborn. Neonatal sepsis was the most prevalent risk factor for hearing loss in 189 (94%) of the newborns, followed by amikacin administration, hyperbilirubinaemia, and severe perinatal asphyxia. Other risk factors for hearing loss among the subjects are as shown in Table Almost half of the subjects  failed at admission screening and 32 (15.9%) failed on discharge. Of these 32, 26 presented for follow up, 1 had died at home and 5 (15.6%) were lost to follow up. Among the 26 that presented 19 (9.5%) still failed screening. Table ABE and severe perinatal asphyxia were significantly associated with failed AABR sreening while ABE had the greatest risk of failed screening during admission screening as shown in Table Eleven babies presented with TSB >20 mg/dl of which 5 had acute bilirubin encephalopathy. Nine of the 11 failed admission screening. At discharge screening, 1 of these 9 had passed, 2 move from severe to mild impairment. Of the 8 that still had impairment at discharge, 1 died at home, 1 was lost to follow up, and 1 moved from mild impairment to pass at follow up screening, and 5 still failed at follow up.Newborns with neonatal encephalopathy stage III from severe asphyxia were 7.5 times more at risk of failing AABR screening than those without asphyxia. Stages I and II encephalopathy were not significantly associated with failed AABR screening. Intraventricular hemorrhage (IVH), ABE, meningitis, recurrent apnoea, vancomycin administration and administration of amikacin for longer than 5 days were significantly associated with the risk of failed AABR screening during the discharge screening as shown in Table The effect of hearing impairment on the newborn, the family and the community is lifelong if intervention is not sought early in life. Early diagnosis and appropriate and timely intervention remain the only way to mitigate its effect on speech, language and cognitive development , 2. The The high prevalence of failed result during admission screening may be partly due to the presence of fluid and debris in the middle ear expected during the first 48 h of life. This is why multistage screening is advisable and as seen in this study, the prevalence of failed results reduced with time. Though not all the subjects presented within the first 48 h of life, hence failed screening in those ones may be due to the risk factors present in them, such was the case with newborns with severe hyprbilirubinaemia in whom 9 out of 11 failed on admission, 8 at discharge and 5 still failed at follow up. Similar result was reported by Lasisi et al in a pilot Newborn hearing screening programme in a rural/sub-urban community in Nigeria, in which a prevalence of failed AABR was 49.4% in the first screening  either from their conditions or interventions received . Though Overall, about a tenth of the high-risk newborns treated in the newborn unit of UCH still failed screening at follow up 6 weeks after discharge, this is higher than 4.4 and 8.5% reported by Olusanya and Akinola respectively , 22 ThisThe multiple screening as seen in this study reduces the likelihood of false failed screening as demonstrated by Mishra . MultiplThe risk factors associated with hearing impairment in our study were similar to the findings of Martinez-Cruz et al.  who repoIn view of the multiplicity of risk factors in some cases and the fact that exact causal relationships between some of the identified risk factors and hearing impairment could not be established with certainty, it is recommended that all these factors be taken into consideration in the management of these newborns especially as it relates to ototoxic medications. For instance, dosage modifications in the presence of other clinical risk factors particularly in settings where drug levels cannot be monitored.The presence of stage III encephalopathy has previously been identified as a definitive marker of hearing loss in asphyxiated infants and its tendency for persistent abnormal AABR in the newborn , 31. ThiThe relative of risk of failed screening due to meningitis, IVH and amikacin in this study is similar to what was reported by Martinez-Cruz et al in their evaluation of high-risk newborns in another developing country .Aminoglycoside induced ototoxicity in newborns has been documented by several authors, , 34–37 iIn conclusion, there is a high prevalence of hearing impairment persisting till 6 weeks post-neonatal care in high-risk newborns in UCH, the majority of which are severe and bilateral. Severe perinatal asphyxia with NNE III, ABE, IVH, meningitis and administration of amikacin for more than 5 days were significant risk factors. Based on the fact that hearing impairment is of public health concern and is a remediable condition when detected early, hearing screening is cost effective but not widely available in resource limited settings such as ours and on the basis of our findings, we recommend that SCBU graduates with stage III encephalopathy, acute bilirubin encephalopathy, intraventricular hemorrhage, meningitis and amikacin therapy for more than 5 days should have mandatory audiologic evaluation at discharge. This should be incorporated into the management protocols of newborn units pending widespread availability of facilities for routine UNHS. The ultimate is to have a universal hearing screening programmes combining TOAE and AABR in order to identify babies with auditory neuropathy as well as those with cochlea abnormalities.This study was carried out in accordance with the recommendations of The National Code for Health Research Ethics, University of Ibadan/University College Hospital Ethics Committee with written informed consent for all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by University of Ibadan/University College Hospital Ethics Committee.LA: Conceptualization and design of the work, drafting of proposal, data collection, analysis and interpretation, drafting of manuscript for publication; TO: Conceptualization and design of the work, drafting and revision of proposal, data analysis and interpretation, drafting and revision of manuscript for publication; BO: drafting of proposal, data interpretation, revision of manuscript for publication; FJ design of the work, revision of proposal, data interpretation, revision of manuscript for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Most older adults prefer to “age in place” and maintain independent regarding activities of daily living (ADL). Dependency in ADL might be caused by frailty. This study explored the relationship between multidimensional frailty and ADL dependency, and if protective factors, derived from a systematic literature review, moderate this relationship. A longitudinal study with a 24-month follow-up was performed among 1,027 community-dwelling older adults. Multidimensional frailty was assessed with the Tilburg Frailty Indicator, and ADL dependency with the Groningen Activity Restriction Scale. Other measures included socio-demographic characteristics and seven protective factors against ADL dependency, such as physical activity and non-smoking. Logistic regression analyses showed that frail older people had a twofold risk of developing ADL dependency in comparison to non-frail older people after 24 months . Analyses with interaction terms indicated that the selected protective factors against ADL dependency did not signiﬁcantly moderate this relationship. Nonetheless, higher levels of physical activity and having suﬃcient ﬁnancial resources decreased the risk of becoming ADL dependent in the overall sample . In conclusion, multidimensional frail older people are at higher risk of developing ADL dependency and the studied factors against ADL dependency did not signiﬁcantly moderate this relationship. To develop prevention strategies for ADL dependency and facilitate aging in place, future studies might explore the relationship between each specific frailty domain and ADL dependency, and the role of (other) moderating factors.