Whole Body Vibration (WBV) might be interesting as it was found to have beneficial effects on a variety of physiological measures. The present study explored the effects of WBV on attention of healthy individuals and adults diagnosed with ADHD.Most of the current treatment strategies of ADHD are associated with a number of disadvantages which strengthen the need for alternative or additional approaches for the treatment of ADHD. In this respect, Eighty-three healthy individuals and seventeen adults diagnosed with ADHD participated in the study. WBV treatment was applied passively, while participants were sitting on a chair which was mounted on a vibrating platform. A repeated measure design was employed in order to explore potential effects of WBV treatment on attention within subjects. Attention (i.e. inhibitory control) was measured with a color-word interference paradigm.A period of two minutes of WBV treatment had significant beneficial effects of small to medium size on attention of both healthy individuals and adults with ADHD. The effect of WBV treatment on attention did not differ significantly between groups.WBV was demonstrated to improve cognitive performance of healthy individuals as well as of individuals with ADHD. WBV treatment is relatively inexpensive and easy to apply and might therefore be of potential relevance for clinical use. The application of WBV treatment as a cognitive enhancement strategy and as a potential treatment of cognitive impairments is discussed. Attention deficit hyperactivity disorder (ADHD) is associated with a reduced quality of life Whole Body Vibration (WBV) can be a beneficial approach to the treatment of adult ADHD.Conventional behavioral and pharmacological treatment strategies of adults with ADHD include, beside others, cognitive behavioral therapy (CBT) and stimulant drug treatment (e.g. using methylphenidate). Both intervention strategies were shown to have beneficial effects on adults with ADHD, although the first-line choice of treatment strategies is often a stimulant drug therapy while they received WBV. While some studies did not find any effect of WBV on cognition (i.e. on short-term memory and reasoning skills) WBV can be described as a training method which exposures the whole body of an individual to low frequency environmental vibration. In contrast to the use of WBV in combination with dynamic exercises in the fields of sports and fitness, a passive application of WBV is realized by holding static poses (i.e. standing or sitting) during the time of exposure to vibration. Beneficial effects of WBV were found on various physiological measures, including balance, mobility, posture control, oxygen uptake, heart rate, blood pressure, blood flow and muscle strength Thus, the aim of the present study was to explore the effects of WBV on attention in a group of healthy individuals and in a clinical sample of individuals with cognitive dysfunctions, i.e. adults with ADHD. The potential value of WBV as a cognitive enhancement strategy and its application for the treatment of cognitive dysfunctions are discussed.Participation in the study was announced to undergraduate students of the University of Groningen, the Netherlands. The description of the study objectives emphasized that the aim of the study was to examine cognition of typically developed students as well as of students with problems of attention. Therefore, a considerable number of students diagnosed with ADHD indicated their interest to participate in the study. In total, 83 healthy individuals and 17 individuals with ADHD took part in the experiment. All participants were undergraduate students from the University of Groningen, the Netherlands. Participation was voluntary and no monetary compensation was offered.Healthy individuals  had a mean age of 22.5 years (SD = 3.7 years), ranging from 18 to 31 years. The self-reported body height of individuals ranged from 163 cm to 205 cm , with a body weight ranging from 50 kg to 105 kg across individuals . Furthermore, the healthy individuals indicated to spend on average 3.8 hours per week on active exercise (SD = 3.6 hours), which ranged from no active exercise at all (0 hours) to 20 hours per week across individuals. None of the healthy individuals reported any history of neurological or psychiatric diseases and none were currently treated with medication known to affect the central nervous system. Furthermore, none of the healthy individuals indicated to suffer from red-green color deficiency which was a prerequisite to perform the Stroop Color-Word Interference task (see below). In addition, all healthy individuals successfully completed two plates of the Ishihara Color Test Individuals with ADHD  had a mean age of 24.2 years (SD = 1.9 years), ranging from 21 to 28 years. According to self-reports, the body height ranged from 159 cm to 190 cm  with a body weight ranging from 45 kg to 101 kg  across individuals with ADHD. Furthermore, individuals with ADHD reported to spend in average 3.2 hours per week on active exercise (SD = 5.1 hours), ranging from no exercise at all (0 hours) to 20 hours per week across individuals. None of the individuals with ADHD indicated to suffer from red-green color deficiency which was again ensured by successful completion of two plates of the Ishihara Color Test 2 (1) = 0.127; p = .721), body height (t (98) = 1.072, p = .286), body weight (t (98) = 0.825, p = .411) and amount of exercise (t (98) = 0.555, p = .580).Healthy individuals and individuals with ADHD did not differ significantly in either of the demographic variables, including age (t(98) = 1.778, p = .079), gender  based on participant’s behavior in the past six months  or based on the participant’s behavior in childhood up to twelve years in age . A symptom was considered to be present, if the answer given to the item was often or very often (score 2 or 3). There were two dimensions, one for inattentive symptoms (nine criteria) and one for hyperactive-impulsive symptoms (nine criteria). To qualify for a clinical diagnosis of adult ADHD, individuals must have met six or more of the nine DSM-IV criteria of inattention and/or hyperactivity-impulsivity in childhood, and at least five of the nine DSM-IV criteria of inattention and/or hyperactivity-impulsivity in adulthood Two scales of the self-report ADHD Rating Scale  were applied, one for current symptoms and one for retrospective symptoms in childhood. The ADHD Rating Scale is a self-report instrument for ADHD symptoms made up of the 18 DSM-IV criteria for ADHD Furthermore, two self-report scales were applied in order to quantify ADHD symptomatology currently and retrospectively. Childhood ADHD symptoms were self-rated with the short version of the Wender Utah Rating Scale (WURS). The WURS contains 25 items which are rated on a five-point Likert scale Vibe 300, Tonic Vibe, Nantes, France). A wooden platform (0.5 m×0.9 m) was mounted on the Vibe 300 to enlarge the platform. On top of the platform, a wooden chair was mounted  was performed. The Stroop Color-Word Interference task measure an aspect of attention, i.e. inhibitory control Stroop Color-Word Interference task were applied, the Color Block Test and the Color-Word Interference Test. In the Color Block Test, 20 squares each printed in one of four possible colors , were presented on a card. The participant’s task was to name the colors of the squares as fast as possible. In the Color-Word Interference Test, a list of 52 color names was presented . Each word was printed in one of four possible colors , however, the color ink of the words was different from the color names (e.g. the word green was printed in blue). The participant was requested to name the ink colors of the words as quickly as possible, thereby ignoring the written color name. In both tests, the time to complete the task was measured. An interference quotient was calculated by dividing the time needed for the Color-Word Interference Test by the time needed for the Color Block Test. The interference quotient represented a measure of attention (i.e. inhibitory control), with a larger quotient indicating more problems in inhibitory control. 12 parallel versions  were designed in order to apply the tests in a repeated measure design.To explore the effects of passive WBV on attention, the Stroop Color-Word Interference task. For these practice trials, four parallel versions of the task were used, separated by a resting period of three minutes between each time the task was performed. The four practice trials were applied in order to minimize practice effects during the experimental trials.At the beginning of the experiment, all participants completed a questionnaire asking for descriptive information including age, sex, body height, body weight, time spent on average per week on exercise as well as red-green color deficiency. Furthermore, participants were asked for any history of psychiatric or neurological diseases as well as pharmacological treatment. For those students who indicated to be diagnosed with ADHD, a psychiatric interview was conducted followed by the completion of four self-report scales of ADHD symptoms. Subsequently, all participants conducted four practice trials of the Vibe 300. The participant was instructed to sit in upright position throughout the whole experiment, the arms on the rest and both feet on the wooden platform. The participant was further instructed to keep body movements to a minimum. The experiment consisted of eight experimental trials. Each trial started with a two-minute period of experimental treatment, either a period of vibration (vibration condition) or a resting period of no vibration (resting condition). Immediately after the experimental treatment, the Color-Word Interference Test and the Color Block Test of the Stroop Color-Word Interference task were performed. The Color-Word Interference Test always preceded the Color Block Test. Subsequently, a resting period of three minutes followed prior to the beginning of the subsequent experimental trial. The eight experimental trials comprised four trials of vibration and four trials of resting. The sequence of the eight experimental trials followed an ABBA-design in order to balance rank order effects (i.e. practice effects) when comparing the two treatment conditions. A schematic drawing of the procedure of eight experimental trials is presented in Prior to the first experimental trial, the participant was requested to take seat on the chair mounted on the The study was approved by the Ethical Committee Psychology (ECP) affiliated to the University of Groningen, the Netherlands. All participants signed an informed consent prior to the study and were debriefed after the assessment. All participants were informed that participation was voluntary and that they had the right to refuse or stop participating in the study at any time.Since the cognitive task were performed repeatedly (eight times) under two different treatment conditions (vibration or resting), mean scores were calculated across the four trials for each treatment condition, separately for healthy individuals and individuals with ADHD. Nonparametric statistical tests (Wilcoxon signed-rank test for dependent samples) were applied in order to compare cognitive performance (mean interference quotient) between the vibration condition and the resting condition, separately for healthy individuals and individuals with ADHD. A significance level of α = .05 was applied for all comparisons. Moreover, effect sizes (Cohen’s d) were calculated for all comparisons. Following Cohen’s guidelines for interpreting effect sizes , negligible effects (d<0.20), small effects (0.20≤d<0.50), medium effects (0.50≤d<0.80) and large effects (d≥0.80) were distinguished In addition, the effect of WBV on cognition was compared between healthy individuals and individuals with ADHD. For this reason, ipsative scores were calculated for each individual by subtracting the mean interference quotient of vibration conditions per participant from the mean interference quotient of resting conditions per participant. Ipsative scores, which indicated the effect of WBV on cognition, were then compared between healthy individuals and individuals with ADHD by applying a nonparametric statistical test for independent samples (Mann-Whitney-U-Test).Furthermore, explorative analyses were carried out in order to examine whether the effects of WBV were determined by demographic variables, including age, gender, body height, body weight and amount of active exercise. This was done by correlating ipsative scores of healthy individuals (indicating the effect of WBV on cognition) with their demographic variables (Spearmen rank correlation). According to Cohen Data analysis revealed that WBV treatment significantly improved attention performance (M±SD) in both healthy individuals  and individuals with ADHD . While the difference in healthy individuals was of small size (d = 0.44), a medium effect (d = 0.64) was found in individuals with ADHD .A separate exploration of the effects of WBV treatment among different subtypes of ADHD showed beneficial effects in all three groups, including patients of the inattentive subtype , the patient of the hyperactive-impulsive subtype  and patients of the combined subtype .A comparison of ipsative scores between healthy individuals  and the entire group of individuals with ADHD  revealed a non-significant difference of small size .Explorative analyses of the association between the effect of WBV treatment and demographic variables in healthy individuals showed that WBV effects were only non-significantly related in small to negligible size to any of the demographic variables including age , body height , body weight  and amount of exercise . Female and male individuals did also not differ significantly concerning the effect of WBV treatment as also indicated by a negligible effect size, Z = −1.258; p = .209, d = 0.19.Stroop Color-Word Interference task. Even though evidence of long-term beneficial effects of WBV treatment on cognition is still lacking, the present effects of WBV on attention are promising as the treatment period was rather short (two minutes), emphasizing the significance of the effect. Furthermore, it was assumed that there is only little room for exercise related improvements of cognition in early adulthood The present study showed in a large sample of healthy young individuals that WBV treatment has a beneficial effect on subsequent cognitive functioning. Already a short interval of two minutes WBV treatment resulted in an acute beneficial effect on attention (i.e. inhibitory control) as measured with the In accordance with the studies showing that patients with neurological conditions can benefit from WBV treatment  Moreover, it has to be emphasized that the present study revealed positive effects of WBV treatment on performance in subsequent cognitive performance and differed in this respect from the majority of previous research in which participants were exposed to WBV at the same time as they performed cognitive tasks If cognition enhancing effects of WBV treatment can be replicated in controlled trials, there are several advantages related to a clinical application of WBV treatment emphasizing its value as a novel strategy in the treatment of cognitive dysfunctions of individuals with ADHD. First, WBV does not interfere with other interventions  and can thus be applied in addition to conventional interventions. Second, WBV is easy to apply and is (in comparison to other methods) cost effective. A WBV device can be set up in private or institutional settings  and short periods of WBV treatment of only a few minutes per day might be sufficient to cause clinically relevant effects. In addition, a high compliance rate is expected as this approach requires only little individual effort (e.g. in form of active exercise). Third, no detrimental side effects are currently known by the application of passive WBV. Fourth, and most importantly, WBV was found to have positive acute effects on attention (i.e. inhibitory control), an aspect of cognition which is crucial for everyday life functioning and which has been found to be impaired in both children and adults with ADHD The present study must be viewed in the context of some limitations. First, with regard to the conclusions aiming at clinical application of WBV treatment, it has to be taken into consideration that the cognition-enhancing effects of WBV treatment on ADHD were observed in a rather small sample (n = 17) of high functioning individuals diagnosed with ADHD. All individuals with ADHD were college students, implying a relatively high level of cognitive functioning. Furthermore, at the time of the assessment, four individuals with ADHD reported to be treated with stimulant medication which compromises the conclusions drawn upon the effects of WBV treatment on cognition. For this reason, the generalization of the observed effects to the population of adults with ADHD and individuals with other neuropsychological disorders might be questioned. However, assuming that there is only little room for improvement in high functioning individuals (ceiling effects), significant effects of small to medium size revealed in two intellectually high functioning groups of people  underline the potential of WBV for the treatment of neuropsychological dysfunctions. A replication of the present findings in a large group of healthy individuals and individuals with neuropsychological dysfunctions appears necessary. Future studies addressing effects of WBV treatment in healthy individuals would benefit from the application of screening instruments for psychiatric disorders (e.g. for depression or ADHD) in order to obtain more homogeneous groups and to exclude individuals with high scores on respective symptom scales suggesting a psychiatric diagnosis.Second, improvements of attention were measured directly after WBV treatment has been applied (acute effects). To establish WBV as a treatment approach, data showing longer lasting effects of cognitive enhancement are required. Therefore, sustained effects of WBV on cognition needs to be explored and should be subject of future research. Longitudinal studies should also take effects of vibratory stimuli on other domains than cognition into consideration, as it was reported that chronic exposure to WBV  is associated with alterations of mood, including fatigue, depression and anxiety Third, the present study focused on a single aspect of cognition, i.e. inhibitory control. However, it remains unsolved whether WBV has a selective effect on only particular aspects of cognition or whether a broad range of cognitive functions can benefit from WBV treatment. Hence, future studies should examine which functions are most sensitive to WBV.Finally, and fourth, so far only little is known about the mechanisms underlying the WBV induced cognitive enhancement, and the present study does not contribute to the understanding of these mechanisms. The present study compared the effects of a two-minute period of WBV treatment with a resting condition in which no vibratory stimuli were applied. The implementation of a variety of control conditions would be necessary in order to explore which elements of WBV treatment are responsible for the cognition enhancing effect. For example, no information was obtained (1) whether it might be efficient enough to stimulate particular body parts (e.g. the hands) of individuals to induce cognition enhancing effects, (2) which settings of vibratory stimuli induce most beneficial effects (i.e. frequency and amplitude) and (3) to which extent the produced noise of the vibrating device contributes to the present results.It was hypothesized that WBV changes muscle length, leading to stimulation of muscle spindles and a reflex response of the muscle In addition, it can be speculated that the beneficial effects on cognition are not only the result of the vibratory stimuli, but also of the noise which is produced by the vibrating device. Unfortunately, a condition controlling for noise was not implemented in the present study design. A recent model based on theoretical considerations on brain arousal and stochastic resonance as well as on empirical evidence suggested that auditory stimuli (background white noise) can be beneficial to cognitive performance


LBW rate is one of the most important health indices in every society. It reveals mothers and their new-born infants' health.Our aim, in the present paper, was to present a new statistical framework for analysis based on path analysis techniques.A prospective study was conducted in two maternity wards,  in Sari, Iran. In this research a check-list containing 25 questions about mother’s demographic information and her new-born infant was prepared. Every new born infant who was born weighing less than 2500 g was entered in our study and just next the newborn infant who was normal all of his/her information use to be taken too, (n = 190). Path analysis, an extension of the regression model, was used in this study.Obviously exactly half of the infants were LBW, and the remainder were normal. There were 97 boys and 93 girls. The percentage of IUGR among mothers who had preterm delivery was 19, while this percentage for mothers who had term delivery was 11.5 . LBW infants were 36.7% unexpected, while this percent for normal infants was 15.5 . Preterm delivery has a significant and direct effect on LBW , and its positive sign of path coefficient shows that if it occurs, the probability of LBW will increase, the second important was IUGR, the results showed unexpected pregnancy had direct effect on LBW but this wasn’t significant .By preventing unnecessary termination of pregnancy and keeping fit, the chances of LBW can be reduced. Low birth weight (LBW) is significantly related to mortality . ConsequOur aim in the present paper was to present a new statistical framework for analysis based on path analysis techniques.A prospective study was conducted during 2010 to 2011 in 2 maternity wards of the main general and teaching hospitals of Sari, Iran. Participants were selected from both private and governmental hospitals. The ethics committee of Mazandaran University of Medical Sciences approved the study. In this research a check-list containing 25 questions about the mother’s demographic information and her new born infants was prepared. Every new born infant who was born less than 2500 g was entered in our study and just next new born infant who was normal all of his/her information was taken too. Mothers who had severe diseases such as cancer, and diabetes and only one pregnancy were included in this study. Scales, which measured weight in both hospitals were the same and were adjusted every day by the supervisor of the ward.Path analysis, an extension of the regression model, was used in this study. A path coefficient, represented as pij, is a standardized regression coefficient indicating the direct effect of variable i on variable j. Accordingly, in a multivariate regression system, it is a partial regression coefficient controlling for other prior variables. Basically, whenever a causal, rather than spurious or coincidental, correlation among a set of variables is suspected, the path analysis is strongly suggested to be done, especially when there is a possibility to sort out the sequence of variables or when it is necessary to distinguish the spurious effect by an intervening factor from the observed relationships  The pathIn the present study, information from 190 mothers and their new-born infants was collected. Obviously, half of the infants were LBW, and the remainders were normal. There were 97 boys and 93 girls. 30.7 percent of mothers had preterm delivery and 13.8 of mothers had Intrauterine Growth Retardation (IUGR). The percentage of IUGR among mothers who had preterm delivery was 19, while this percentage for mothers who had term delivery was 11.5 . 75.7% of cases had intentional pregnancies and the rest of had unexpected pregnancies. LBW infants were 36.7% unexpected, while this percent for normal infants was 15.5 . Mothers 61.9% had 2 pregnancies , 22.8% had three pregnancies, 10.1% had four pregnancies and the rest of them had more than 4 pregnancies; Since the correlation matrix, beside theoretical concepts, is a great full for achieving Path analysis model, this was calculated .As it seen in 1 s are unobserved exogenous variables and only education is an observed endogenous variable. In the next stage, output path diagram was reached in In the current input path diagram there are 17 variables, e The straight lines show the direction of the path from the exogenous variables towards the indigenous variables. In the last decade, a lot of statistics were presented for testing the model  ; there aFor the RMR which is the absolute fit index, the closer value to zero shows a better fit  . NFI, TLPreterm delivery had a significant direct effect on LBW , and its positive sign of path coefficient shows that if it occurs, the probability of being LBW will increase. The second important entity was IUGR, the results showed unexpected pregnancy had a direct effect on LBW but this wasn't significant .The purpose of this study was to identify and confirm the direct and indirect effect of factors on LBW. A rise of LBW rate in a country increases neonatal mortality and also infant mortality rate, which is an important indicator of the level of public health in the country . LBW infPath analysis is superior to ordinary regression analysis as it provides and explains both casual relations and the relative importance of alterative paths on influence . The patUnivariate analysis revealed factors related to low birth weight, including, marriage age, mother’s age, gestational age, BMI, first pregnancy age, distance between last pregnancy and recent pregnancy, birth weight of last child, and finally infant weight and obviously all of them had a positive effect on weight of new born infants, while unexpected pregnancy had a negative effect and caused LBW. Somehow these findings are in agreement with those reported by some studies about risk factors of LBW , 25. In Unfortunately path analysis cannot demonstrate causality, and cannot be used in explanatory situations thus finding some method that has path analysis’ properties and can be used for explanatory purposes, would be very useful. Because of path analysis prerequisite, which are variables used in the model, must have at least interval scale finding some method can be used when variables have nominal scale is beneficial. Using Bayesian path analysis for the next investigation is strongly recommended.


Importantly, associations were highly significant even when few ADHD symptoms were reported. Compared to the hyperactivity component, the inattention trait was particularly strongly associated and remained significant after controlling for depression/anxiety symptoms. Our study confirms previous findings and significantly adds to existing literature especially for an age-group that has not been well-studied. Our results suggest that ADHD symptoms continue to be associated with ill-health and functional impairment in mid-life and are, therefore, likely to be a major, previously unrecognized source of late-life morbidity with associated social and economic costs. Thus, there is a compelling need for better understanding and development of age-appropriate approaches to the diagnosis and treatment of ADHD in mid- to late-life.Attention deficit/hyperactivity disorder (ADHD) is the most prevalent childhood psychiatric condition. It frequently persists into adulthood and can have serious health and other adverse consequences. The majority of previous adult ADHD studies have focused on young adults so that relatively little is known about ADHD symptoms and their effects in mid and late life. In addition, effects of subclinical levels of attention deficit and hyperactivity have not been studied in detail. In this study we investigated ADHD symptoms and related impairment in a large population-based sample of middle-aged Australian adults . Applying the WHO adult ADHD Self Report Screener (ASRS) we observed that 6.2% of participants had scores that were previously associated with ADHD diagnosis. No significant gender difference in the distribution of ASRS scores was observed. Multiple regression analyses indicated strong positive correlations between symptoms of ADHD and depression/anxiety and significant negative associations ( Attention Deficit/Hyperactivity Disorder (ADHD) is a treatable neuropsychiatric disorder characterized by inattention, excessive motor activity and impulsivity th edition, Text Revision (DSM-IV-TR) Clinical diagnosis of ADHD typically follows categorical definitions codified in The Diagnostic and Statistical Manual of Mental Disorders, 4While awareness of adult ADHD has increased over the last decade, we know relatively little about the disorder in older adults. Few studies There has been increasing recognition that midlife represents a critical period where interventions could lead to healthier and more productive ageing. However, this age-group has been largely neglected with respect to mental health research as much of the focus is on the young or the elderly. In this study we investigated the impact of self-reported ADHD symptoms on a range of measures of health, work, social life, relationship, well-being and anxiety/depression symptoms in a large population-based sample of middle-aged adults. We used the World Health Organization's adult ADHD Self Report Screener (ASRS) All participants gave written informed consent to be included in the Personality and Total health (PATH) project. The study was approved by the Human Research Ethics Committee of The Australian National University.The study sample was drawn from the middle-aged cohort of the PATH Through Life Project, which is a longitudinal study of mental health and ageing The present study used data from the third wave of assessment , which included 2179 individuals aged 47–54 years (mean age 50.7±1.5 years). Twenty-five participants (1.2%) failed to complete the ASRS questionnaire. These non-responders did not significantly (p>0.05) differ from the responders with respect to any of the sociodemographic variables. A further 63 participants who reported having epilepsy, brain tumor/infection or severe head injury were excluded, leaving a sample of n = 2092  available for this investigation. One participant reported being prescribed Dexamphetamine, which is used for treating ADHD. Inclusion or exclusion of this participant did not affect the result of our analyses (only results with this participant excluded are reported).All self-report measures used in this study were obtained using validated instruments. The ASRS was developed by the World Health Organization and the short form of the screener consists of a checklist of six questions regarding symptoms of ADHD based on the diagnostic criteria of DSM-IV-TR Categorical measures related to employment status, financial stress and married/cohabiting relationship were generated from responses to questions such as “How would you describe your current employment status?”, “Have you or your family had to go without things you really needed in the last year because you were short of money?”, “Are you currently in a relationship with someone?” and “How many times have you been married or lived in a de facto relationship?”. The 7-item short form of Dyadic Adjustment Scale (DAS-7) was used to measure adjustment in a married or cohabiting relationship. An equally weighted sum of the response scores for the seven items was used the DAS-7 total score Health-related quality of life was measured using RAND-12, which contains 12 items from the eight scales of the RAND-36 Health Status Inventory The three separate components of subjective well-being – positive affect , negative affect (reflecting subjective distress and unpleasurable engagement) and life satisfaction 2R value between each step and the p value associated with the 2R change were noted. For simplicity in interpretation we report results that were significant at the stringent α level of 0.01 instead of the more commonly used level of α = 0.05. However, the majority of results remained significant after applying Bonferroni corrections at an α = 0.05.All statistical analyses were conducted using SPSS 18 (Chicago: SPSS Inc.). Means and standard deviations were computed for the ASRS total score, ITS and HTS. Comparisons between males and females were performed using Student's t-tests and Pearson's Chi-square tests for the continuous and categorical ASRS measures respectively. Associations between the symptoms of ADHD and depression/anxiety symptoms, employment status, financial problems, RAND-12, PAS, NAS, SWLS, DAS-7 and LSNS-6 scores were analyzed using linear or logistic regressions as appropriate. Age, sex and total years of education were included as covariates in all models. Depression and anxiety symptoms were included as additional covariates in models as indicated. Regression models were generated by entering the covariates first, followed by the predictors. Change in For each individual item on the ASRS questionnaire, the frequency of participants responding to each point of the response scale is shown in r = 0.199, p<0.001), we observed that even when participants reported “often” or “very often” for all inattention items (n = 23) their HTS scores were distributed over the entire range of the scale  were normally distributed in our sample with means and standard deviations of 5.3±2.7 and 2.8±1.7, respectively. There was no significant difference between males and females for either trait, although a non-significant trend towards higher ITS in males was observed . While Ihe scale . A similhe scale . Hence, We observed significant associations between ADHD symptoms and both depression and anxiety symptoms . CompareIn our sample 8.0% and 16.7% of participants reported being currently unemployed and having financial problems respectively. ITS and HTS do not significantly alter the odds of being currently employed although there was a trend towards lower odds of being employed for higher ITS . In addip<0.01). No significant difference was observed when “never being married or in a relationship” was included in the analysis. Significant associations are also observed between ITS and measures of cohabiting/marital relationship adjustment (DAS-7), health related quality of life (RAND-12), subjective well-being (PANAS and SWLS), social interactions (LSNS-6) and affect . We included assessment of multiple symptomatic and functional domains affected by ADHD to provide a comprehensive description of functional impairment, while earlier studies have largely focused on health status and workplace impairment. We report extensive data on individuals with fewer and/or milder ADHD symptoms (ASRS strata II and III comprising of >30% of the participants), a group that has not previously been studied in detail. Importantly, we report significant impairment in health, personal and social domains in this group, which often goes unnoticed. In addition, we report results for continuous measures of ADHD symptoms, which allows us to distinguish between inattention and hyperactivity related impairment. Finally to better understand the co-occurrence between ADHD and depression/anxiety symptoms we clearly show how the regression results were affected by the inclusion or exclusion of depression/anxiety symptoms in the model. This comparison aids in gauging the unique contribution of ADHD symptoms to impairment.This study has several limitations. First, information on ADHD symptoms during childhood was unavailable and hence we could not assess participants clinically using the current diagnostic criteria. Similar limitations also apply to measures of depression and anxiety symptoms, which were not diagnosed in clinical terms. Nevertheless, the associations we observed between ADHD symptoms and functional impairment was very similar to those reported previously in both patient and population samples, albeit in a younger age group. Second, all measures were based on self-reports, which might not be completely accurate (e.g. social desirability and current emotional state could introduce biases In conclusion, we observed that a significant proportion of middle-aged individuals in the general population report impairment associated with ADHD symptoms – especially inattention symptoms with both males and females being equally affected. Irrespective of whether or not these individuals meet all the criteria required for a clinical diagnosis of ADHD, the significant functional impairment and depression/anxiety symptoms they experience clearly demonstrates that the presence of these symptoms constitutes a substantial burden for middle-aged adults. For societies with a large aging population this burden, which is currently unrecognized, is likely to result in significant costs for individuals as well as the community. Impairment associated with ADHD symptoms is responsive to interventions in children, adolescents and young adults


The Attention Network Test (ANT) generates measures of different aspects of attention/executive function. In the present study we investigated whether adults with ADHD performed different from controls on measures of accuracy, variability and vigilance as well as the control network. Secondly, we studied subgroups of adults with ADHD, expecting impairment on measures of the alerting and control networks in a subgroup with additional symptoms of affective fluctuations.n = 58; controls n = 56) performed the ANT and completed the Adult ADHD Rating Scale (ASRS) and the Mood Disorder Questionnaire (MDQ). The latter was used to define affective fluctuations.A group of 114 adults (ADHD p = .005) and their score on a test of intellectual function (WASI) significantly lower than in the control group (p = .007). The two groups were not significantly different on measures of the three attention networks, but the ADHD group was generally less accurate (p = .001) and showed a higher variability through the task (p = .033).The sex distribution was similar in the two groups, but the ADHD group was significantly older (n = 22) were slower (p = .015) and obtained a lower score on the alerting network (p = .018) and a higher score on the conflict network (p = .023) than those without these symptoms. The significance was retained for the alerting network (p = .011), but not the conflict network (p = .061) when we controlled for the total ASRS and IQ scores.The significance was only retained for the accuracy measure when age and IQ scores were controlled for. Within the ADHD group, individuals reporting affective fluctuations , but slower and more distracted by conflicting stimuli than the subgroup without such fluctuations. The results suggest that the two ADHD subgroups are characterized by distinct patterns of attentional problems, and that the symptoms assessed by MDQ contribute to the cognitive heterogeneity characterizing groups of individuals with ADHD. Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder characterized by motor restlessness and symptoms of impulsivity and inattention. The prevalence in the child population is estimated to be about 5%, and the disorder frequently persists into adulthood -4, with Neuropsychological studies have related changes in neural networks involving the frontal lobe to impairment on tests of attention, primarily those defined within the concept of executive function (EF) ,8. The iPosner and colleagues have presented one such model . Their AThe Attention Network Model has been used to develop test paradigms that have become popular during the last decades. Fan and collaborators developed the Attention Network Test (ANT) ,26, and The impact of ADHD symptoms on cognitive function is well documented e.g., ,31). Rec. Rec31])The aim of the present study was twofold. First, we investigated ANT results in a group of adults with ADHD and a control group from the general population. From earlier studies we expected the ADHD group to show impairment on the ANT measure of the control network, as well as on measures of accuracy, vigilance and variability. Secondly, we investigated ANT results in an ADHD subgroup reporting affective fluctuations. From earlier studies we expected that high arousal and EF impairment in this subgroup would influence their results on the alerting and control networks. Finally, we asked if the results would change when we controlled for ADHD symptoms and intellectual function.The present study included a subset of adults participating in a Norwegian national study of adults with ADHD.The adults with ADHD were recruited from a national registry of adults diagnosed with ADHD in Norway from 1997 to May 2005. Three national expert committees for ADHD/Hyperkinetic disorders were responsible for the diagnostic assessment, based on information from clinical records provided by the referring clinicians. The records included information collected and evaluated according to the official diagnostic system in Norway, the ICD-10. However, allowance was made for the inattentive subtype in DSM-IV to be sufficient for the diagnosis, so that the assessment also could be comparable with the DSM-IV. A total of 1700 invitation letters were sent from 2005 to 2007, mainly targeting individuals referred after year 2000. Adults with ADHD were also referred directly from Norwegian psychiatrists or psychologists to include individuals diagnosed later than May 2005. These adults were assessed by specialists in clinical psychiatry or psychology according to the national guidelines based on the criteria used by the national expert committees, but without their mandatory evaluation.The control group was recruited through a random selection from the Norwegian population, using the database of The Medical Birth Registry of Norway (MBRN), which includes all Norwegians born after January 1st 1967. Invitation letters were sent to a randomly selected sample of 2963 individuals who were between 18-40 years old. In addition, a subsample was recruited by different advertisements. The control group was not screened for ADHD before entering the study. However, the prevalence in the population was expected to be low, as the estimate among Norwegian primary school children has been reported to be only 1.7 percent . All parWe invited randomly selected participants from the main study, living geographically close to the city of Bergen, to take part in a neuropsychological examination including the Attention Network Test and two subtests from the Wechsler Abbreviated Scale of Intelligence (WASI) . The ADHTwo subtests from the WASI, the Vocabulary and Matrix Reasoning, were used to estimate intellectual function according to the norms presented in the test-manual . The exaThe Adult ADHD Self-Report Scale (ASRS) is a rating scale designed to measure current ADHD symptoms, representing the 18 DSM-IV symptoms of ADHD. The symptoms were rated on a 5-point scale (0 = never/seldom and 4 = very often), yielding a total score between 0 and 72. In this study we included the total ASRS score .The Mood Disorder Questionnaire (MDQ) was included to define a subgroup with affective fluctuations ,45. The The MDQ was originally designed and validated as a screening instrument for bipolar spectrum disorder ,45. MoreThe Attention Network Test (ANT) used in the present study is the original standard version , downloaThe ANT was administered in a quiet test room. It was run on E-Prime software, on a stationary computer with a 17" computer screen. The participants sat at a comfortable distance from the screen and responses were collected via two input keys on the keyboard, corresponding to a left or right pointing arrow. Each administration was done individually with a research technician present in the room. The participants were asked to decide as quick as possible the direction of the middle arrow by pushing the left or right mouse button. The completion time was approximately 25 minutes.d = 0.20 is small, d = 0.50 is moderate; d = 0.80 is large) [SPSS, version 18, was used to analyze group differences between individuals with ADHD and controls. The three network scores were included in a multivariate analysis within the GLM package, with group as a fixed factor. Univariate post-hoc tests with Tukey corrections for multiple comparisons were run to investigate group differences on each of the three networks. The analyses were repeated by including covariates, i.e., demographic variables that were significantly different between the groups. Group comparisons on the ANT measures of accuracy, variability and vigilance were investigated by using separate univariate analyses of variance within the GLM package, including covariates in case of statistically significant results. The statistical procedure was repeated within the two ADHD subgroups, by including MDQ score as a fixed binary factor. Effect sizes  were calculated and interpreted according to general guidelines (s large) .t = 2.86, p = .005, d = .53) and scored significantly lower on the test of intellectual function than the control group . The two groups did not differ in gender distribution. As expected, the total ASRS score was considerably higher in the ADHD than in the control group  , and higher ASRS score  than the MDQ- group  did not differ with respect to age (mean age = 34.2/33.2). However, the group of individuals defined as MDQ+ obtained a significantly lower total IQ , including the reaction-time measures of the three attention networks, showed a non-significant effect of group, Wilks' Hit reaction time (RT) for correct responses was not significantly different between the ADHD and the control group, but the total number of hits was significantly lower in the ADHD group than in the control group, F = 12.8, p = .001, d = .71. The difference remained significant after including age and intellectual function as covariates, F = 12.4, p = .001. The ADHD group committed significantly higher number of omission errors than the controls, F = 13.6, p< 001, d = .68, a difference that was retained when age and intellectual function were included as covariates, F = 13.4, p < .001.SE of all blocks, measuring the consistency of responses across the task, was not significantly different between the two groups. The variability SE score, measuring the within respondent variability throughout the task, was significantly higher in the ADHD than in the control group, F = 4.2, p = .033, d = .71. A trend towards statistical significance was retained when intellectual function was included as a covariate (p = .052), but not when age was added in the statistical model.The RT block change, measuring the slope of change in reaction time throughout the test, did not differ between the ADHD and control group. The SE block change, measuring the slope of change in standard error of reaction time between the three blocks, was significantly higher in the ADHD than in the control group, F = 5.0, p = .027, d = .43. The difference was still significant when intellectual function was included as covariate, F = 4.4, p = .038, but not when adding age in the statistical model.The The results for the selected ANT variables for the two ADHD subgroups are shown in the two right panels of Table λ = .836, F = 3.5, p = .021. Post-hoc tests showed that the MDQ+ subgroup obtained an overall lower score on the alerting network than the MDQ-subgroup, F = 6.0, p = .018, d = .64. On the conflict network, the MDQ+ subgroup obtained a significantly higher score than the MDQ- subgroup, F = 5.3, p = .026, d = .62, indicating that the former was more distracted by incongruent flankers than the latter. The group difference was non-significant on the orienting network.A MANOVA, including the reaction-time measures of the three attention networks, showed a statistically significant difference between the two MDQ-groups, Wilks' λ = .837, F = 3.3, p = .027. A statistical significant difference was confirmed by the univariate analyses for the alerting network, F = 7.1, p = .011, but not for the conflict network, p = .061.A MANCOVA including the total ASRS and IQ scores as covariates was still statistically significant, Wilks' hit reaction time for correct responses was significantly slower in the MDQ+ than in the MDQ-subgroup, F = 5.3, p = .025, d = .90. This difference was no longer statistically significant when the total IQ and ASRS scores were included as covariates (p = .078). The overall number of hits across the three blocks and the number of omissions were not significantly different between the two subgroups.The variability SE, measuring within respondent variability, the SE block change, measuring the slope of change in standard error of reaction time between the three blocks, and the RT block change, measured as the slope of change in RT throughout the task, were not significantly different between the two ADHD subgroups.The The present study showed that adults with ADHD did not differ from controls on ANT measures of the three attention networks, but they showed a lower accuracy, a higher intra-individual variability, and lower vigilance across the task. The effect sizes were mainly moderate, but only the accuracy measures retained statistical significance when we controlled for age and intellectual function. An important and novel aspect of the present study was the inclusion of a binary MDQ score to define an ADHD subgroup with affective fluctuations. In this subgroup we found an impact on the alerting and control networks, and on the measure of hit reaction time. The subgroup was significantly more distracted by conflicting stimuli and slower to respond. At the same time their results on the measure of the alerting network suggest that they were more alert. Furthermore, the total ASRS and IQ scores had a major impact on the reaction time and the control network in this ADHD subgroup, while the alerting network was left unaffected.Given the original description of the test, it was somewhat surprising that adults with ADHD and controls did not differ on any measure of attention networks. According to findings in previous studies we expected to find impairment of the control network in the ADHD group ,28,50. FArousal and alertness are known to be affected in ADHD , with a The present study showed impairment in the ADHD group on measures of accuracy, variability and vigilance, supporting findings from earlier studies of children ,55,56 anThe present study has limitations related to the diagnosis of ADHD and the definition of affective fluctuations. The adults with ADHD included in the study were evaluated by several clinicians before inclusion in the study, probably yielding a large heterogeneity within the ADHD group. On the other hand, our ADHD sample probably represents adults with an ADHD diagnosis as encountered in a clinical setting. Affective fluctuations were assessed according to a self-report questionnaire, originally designed to measure symptoms of bipolar spectrum disorders. However, it has been shown that most adults with ADHD with a positive MDQ score do not fulfill criteria for this disorder , and thaThe present study suggests that adults with ADHD are less accurate, have a higher level of variability and a lower vigilance than adults without ADHD, and that affective fluctuations make adults with ADHD more alert, but slower and more distracted by conflicting stimuli. Our results indicate that the cognitive heterogeneity among adults with ADHD at least partly is explained by affective symptoms. By these results the present study emphasizes the importance of characterizing and taking these symptoms into account in research and clinical work with adults with ADHD.The authors declare that they have no competing interests.AJL: Design, statistical analyses and writing of the manuscript.SA: Data analysis, comments on the manuscript.HH: Cognitive assessment, comments on the manuscriptKP: Comments on the manuscript.AH: Comments on the manuscript.JH: Head of the national ADHD project, comments on the manuscript.All co-authors have read and accepted the final version of the manuscript.


This article addresses the boundary layer flow and heat transfer in third grade fluid over an unsteady permeable stretching sheet. The transverse magnetic and electric fields in the momentum equations are considered. Thermal boundary layer equation includes both viscous and Ohmic dissipations. The related nonlinear partial differential system is reduced first into ordinary differential system and then solved for the series solutions. The dependence of velocity and temperature profiles on the various parameters are shown and discussed by sketching graphs. Expressions of skin friction coefficient and local Nusselt number are calculated and analyzed. Numerical values of skin friction coefficient and Nusselt number are tabulated and examined. It is observed that both velocity and temperature increases in presence of electric field. Further the temperature is increased due to the radiation parameter. Thermal boundary layer thickness increases by increasing Eckert number. There is a substantial interest of the recent researchers in the flows of non-Newtonian fluids. Such motivation in these fluids is mainly because of their use in the industrial and technological applications. Many materials like mud, pasta, personal care products, ice cream, paints, oils, cheese, asphalt etc. are non-Newtonian fluids. Most biological fluids with higher molecular weight components are also non-Newtonian in nature. The usual properties of polymer melts and solutions together with the desirable attributes of many polymeric solids, have given rise to the world-wide industry of polymer processing. The non-Newtonian fluids in particular have key importance in geophysics, chemical and nuclear industries, material processing, oil reservoir engineering, bioengineering and many others. Rheological properties of all the non-Newtonian fluids cannot be predicted using single constitutive equation (unlike the case of viscous fluids). Therefore many models of non-Newtonian fluids are based either on “natural” modifications of established macroscopic theories or molecular considerations. The additional rheological parameter in the constitutive equations of non-Newtonian fluids are the main culprit for the lack of analytical solutions. The resulting equations are more complex and higher order than the Navier-Stokes equations. Hence these equations have been attracted from modelling as well as solutions point of view. The advancement in the study of non-Newtonian fluids has been made even by the recent investigators  third grade fluid over a porous stretching surface. Here the fluid is electrically conducting in the presence of applied magnetic If The local skin friction coefficient is defined asThe velocity and temperature can be expressed in the set of base functionsThe initial guesses The zeroth order problems areSetting th order of approximation in We note that the series solutions (33) and (34) contain the non-zero auxiliary parameters 1E and Eckert number This section illustrates the impact of physical parameters. The results are displayed graphically in the The flow of third grade fluid and heat transfer in the presence of thermal radiation and Ohmic dissipation are examined. The graphs are prepared to study the influence of the pertinent flow parameters including the second grade parameter (The effect of third grade parameter The maximum velocity is attained for higher values of electric parameter Effect of suction parameter, unsteadiness parameter and Reynolds number on boundary layer thickness is similar in a qualitative sense.Effects of The velocity field Magnitude of skin friction coefficient Electric parameter


Pseudomonas syringae pv. tabaci (Pstab) is the causal agent of wildfire disease in tobacco plants. Several pathovars of Pseudomonas syringae produce a phytotoxic extracellular metabolite called coronatine (COR). COR has been shown to suppress plant defense responses. Interestingly, Pstab does not produce COR but still actively suppresses early plant defense responses. It is not clear if Pstab produces any extracellular metabolites that actively suppress early defense during bacterial pathogenesis.Pstab extracellular metabolite extracts (Pstab extracts) remarkably suppressed stomatal closure and nonhost hypersensitive response (HR) cell death induced by a nonhost pathogen, P. syringae pv. tomato T1 (Pst T1), in Nicotiana benthamiana. We also found that the accumulation of nonhost pathogens, Pst T1 and P. syringae pv. glycinea (Psgly), was increased in N. benthamiana plants upon treatment with Pstab extracts . The HR cell death induced by Pathogen-Associated Molecular Pattern (INF1), gene-for-gene interaction (Pto/AvrPto and Cf-9/AvrCf-9) and ethanol was not delayed or suppressed by Pstab extracts. We performed metabolite profiling to investigate the extracellular metabolites from Pstab using UPLC-qTOF-MS and identified 49 extracellular metabolites from the Pstab supernatant culture. The results from gene expression profiling of PR-1, PR-2, PR-5, PDF1.2, ABA1, COI1, and HSR203J suggest that Pstab extracellular metabolites may interfere with SA-mediated defense pathways.We found that the Pstab extracts suppress plant defense responses such as stomatal closure and nonhost HR cell death induced by the nonhost bacterial pathogen Pst T1 in N. benthamiana.In this study, we found that  Pseudomonas syringae species survive on the plant leaf surface as epiphytes  were used for this experiment. The bacterial pathogens were cultured in KB medium with appropriate antibiotics overnight at 28°C on a rotary shaker (250 rpm). Bacteria were collected by centrifugation (3500 rpm/10 min) and resuspended in MES buffer . The bacterial suspension was syringe-infiltrated to fully expanded N. benthamiana leaves for determining bacterial growth (for Psgly) and nonhost HR cell death (for Pst T1). To determine whether the bacterial growth is promoted by Pstab extracts, the nonhost pathogen Psgly that does not induce HR cell death was inoculated with either MG medium or the Pstab extracts. The bacterial population in the apoplast was examined for 0, 1, 3 and 5 days. For nonhost HR cell death assay, each metabolite sample was infiltrated with Pst T1 using a needle-less syringe on six-week-old N. benthamiana leaves. We selected fully extended upper leaves for the inoculation. In all experiments, the extracts from Pstab supernatant and MG medium were included as positive and negative controls. To eliminate any contaminating proteins in Pstab extracts, the extracts were treated at 95°C for 5 min. Two additional nonhost bacterial pathogens, Psp and Psm, including Pst T1 were inoculated along with the boiled Pstab extracts in N. benthamiana. Symptoms of nonhost HR cell death were determined from 12 hrs to 72 hrs after inoculation.Five Pstab extracts suppressing nonhost HR cell death, we used several Avr-R gene combinations (35S:AvrPto-35S:Pto and 35S:Avr9-35S:Cf9) [Agrobacterium containing the respective constructs were cultured in 5 mL LB medium containing respective antibiotics for 24 hr at 28°C. The bacterial culture was centrifuged at 1,500 g for 10 min and resuspended in 5 mL of infiltration buffer (10 mM morpholinoethane sulfonic acid (MES) and 200 mM acetosyringone). Then, the culture was incubated at room temperature for three to five hrs. After incubation, bacterial cells were harvested by centrifugation and diluted to 5×105 CFU/ml  and 2×107 CFU/ml (Cf9 and AvrCf9) for infiltration. Pto and AvrPto, and Cf9 and AvrCf9 constructs were mixed to 1:1 ratio before infiltration to N. benthamiana leaves.To determine the specificity of 35S:Cf9) ,52. AgroPstab extracts were resuspended in 150 μl of 80% methanol in H2O and analyzed using a UHPLC-ESI(-)-qTOF-MS instrument (Waters Premier qTOF) with a reverse-phase column , which was maintained at 60°C, and components were eluted using a multi-step gradient from 95 to 30% A  over 30 min, 30 to 5% over 3 min and 5 to 95% A over 3 min at a flow rate 0.56 mL/min. The complementary eluent B was acetonitrile. TOF-MS spectra were acquired under the following conditions: spectral acquisition rate: 3.13 per second; detector voltage: 2600 V; threshold: 2037; ESI: -4500 V; desolvation temperature: 300°C; nebulizer pressure: 350 kPa; interface: 100°C. Mass measurement accuracy was within 20 ppm. The MS system was calibrated using sodium formate, and raffinose was used as the lock mass for internal calibration. Data obtained from metabolite analyses were processed using MarkerLynx 4.1 (Waters) for accurate data mass extraction. Relative abundance was normalized by dividing each peak area by the value of the internal standard peak area.The dried N. benthamiana leaf samples were collected at various time points after treatments. RNA was isolated from leaves at 0, 6 and 12 hrs after inoculation with Pst T1 + Pstab extracts (Pstab ext./Pst T1) or with Pst T1 + MG medium extracts as control (MG ext./Pst T1). All RNA samples were extracted using Qiagen RNeasy Mini Kit , and cDNA was synthesized using Superscript III reverse transcriptase . Quantification and purity of RNA and cDNA were determined using NanoDrop . Expressions of PR1, PR2, PR5, PDF1.2, ABA1, and COI1, representative genes for each ABA, SA and JA signal pathway, and HSR203J for HR cell death, were determined by quantitative real-time PCR. At least three biological replicates of each sample and three technical replicates of each biological replicate were analyzed for real-time PCR analysis. The amount of transcripts for each gene in different RNA samples was normalized with the transcripts of the internal control gene NbActin to ensure an equal amount of cDNA was used for individual reactions.To examine the expression patterns of genes involved in SA-, JA- and ABA-related plant signal transduction pathways, The authors declare that they don’t have any competing interests.Pstab extracts and carried out mass-spectrometry analysis for Pstab extracts; SRU carried out confocal images of GFPuv-expressing bacteria in stomata and apoplast space; LWS designed bacterial metabolomics work and edited this manuscript; KSM participated in designing and coordinating the project. SL and KM wrote the manuscript. All authors read and approved the final manuscript.SL performed major parts of the experiments; DY prepared P. syringae pv. tabaci using UHPLC-qTOF-MS. List of extracellular metabolites secreted from Click here for filePR5, PDF1.2, ABA1, HSR203J and COI1 genes after treating with MG or Pstab extracts in N. benthamiana. The expression level of PR5, PDF1.2, ABA1, HSR203J and COI1 as determined by qRT-PCR after treatment of Pstab extracts. Gene expression analyses were performed using three biological replications. Bars represent the means ± standard deviation (SD). Same letters above bars indicate no statistically significant difference (P<0.05) among plant genotypes for a given time point using one-way ANOVA followed by LSD test analysis. The qRT-PCR data were normalized to NbActin transcript and shown as relative to that of target gene expressions in 0 hr N. benthamiana leaves without any treatment. Expression patterns of Click here for file


Attention deficit hyperactivity disorder (ADHD) is the most commonly diagnosed neurobehavioural disorder in childhood, affecting over 5% of children worldwide. As well as the core symptoms of inattention, hyperactivity and impulsivity, patients often exhibit learning difficulties and impairment in social functioning. The frequency of referral is higher for boys than for girls (about 2:1), and girls are generally older at the time of referral.Pharmacological therapy is considered the first-line treatment for patients with severe ADHD and severe impairment. Stimulant medications are licensed in the UK for the management of ADHD in school-age children and young people, and are effective in controlling ADHD symptoms.While immediate-release preparations of methylphenidate (MPH) have proven effective in the treatment of ADHD, there are a number of problems associated with their use, most notably compliance, stigma and medication diversion. Modified release preparations are now available that overcome the need for multiple daily dosing, and which offer different MPH release profiles, thereby enabling the physician to match the medication to the patient's particular requirements.®) is illustrated with case studies.This review describes the diagnosis, referral and treatment pathways for patients with ADHD in the UK and the practical considerations when initiating pharmacological treatment. The clinical experience of treating ADHD with a modified-release MPH preparation (Equasym XL Attention deficit hyperactivity disorder (ADHD) is the most commonly diagnosed neurobehavioural disorder in childhood; a recent meta-regression analysis estimated a worldwide prevalence of 5.29% among children and adolescents . It is cIn the UK, patients with suspected ADHD, identified through concerns from school  or family members, are brought to the attention of the general practitioner (GP) via parents. Children are then referred for further specialist assessment for ADHD. The referral pathway varies in different parts of the country, with paediatricians carrying out the diagnostic assessment in some areas and child psychiatrists in others; some centres provide a joint service involving both paediatricians and child psychiatrists.Children referred to their GP usually present with concerns of inattention, hyperactivity and impulsivity. Symptoms impact on their academic achievements and social interaction at school; home life can also be very difficult, as children with ADHD are constantly active and demanding, which tends to cause conflicts with their families. The frequency of referral is higher for boys than for girls (about 2:1), and girls are generally older at the time of referral. This is probably because girls are more likely to have the predominantly inattentive subtype of ADHD , which, Pharmacological therapy is considered the first-line treatment for patients with severe ADHD and severe impairment . Stimula®) and MPH-MR 30:70 (Equasym XL®) have been shown to be equivalent to twice-daily MPH-IR [®) is equivalent to MPH-IR, three times daily, although at a 20% higher dose [Immediate-release formulations of MPH (MPH-IR) have been used since the 1960s to control ADHD symptoms. With MPH-IR, peak plasma concentrations and optimum behavioural effects are reached approximately 1.5-2.0 h after administration . The limy MPH-IR ,19, whilher dose -23. HaviAt the start of treatment with any MPH formulation, careful dose titration is necessary. IR and long-acting formulations of MPH can both be used to initiate treatment of ADHD -26. In sFrom a clinical perspective, the regimen that achieves satisfactory symptom control at the lowest total daily dose and with the fewest adverse events (AEs) should be employed. In cases where treatment effects wear off too early, patients can be given an extra dose of MPH-IR in the late afternoon or early evening if needed ,26; for The choice between treatment options should be determined on an individual basis, with particular consideration of the requirement for symptom control in the latter part of the day. MPH treatment is generally well tolerated by patients and severe AEs are rare. Increased insomnia, other sleep-related problems and reduced appetite are common, and there is some evidence for increased levels of emotionality, social withdrawal, nausea and stomach aches, although it is not clear which of these AEs are related to pre-existing problems associated with ADHD prior to treatment . FurtherLong-term side effects of MPH include weight loss from reduced appetite and reduction in height velocity ; the magThis MPH-MR 30:70 formulation of MPH contains a 30:70 ratio of IR to DR MPH by weight . It usesThe efficacy of MPH-MR 30:70 in children with ADHD has been demonstrated in three 3-week randomised, double-blind studies: a placebo-controlled non-inferiority study compared with a twice-daily IR formulation  and a paThese trials show that MPH-MR 30:70 is an effective and well tolerated once-daily treatment for ADHD ,27,33-37Diagnostic and Statistical Manual, fourth edition (DSM-IV) criteria and which assesses the core symptoms of ADHD: concentration, hyperactivity and impulsivity. The P4 was designed by one of the consultant child psychiatrists in the team and has been in use for 15 years as one of the tools available for screening the core symptoms of ADHD. The questionnaire has shown good correlation with information received from school and home in identifying children with ADHD, although it has not been validated in population studies. The diagnostic assessment in our unit involves: (1) diagnostic interview with the parent/carer and the child/young person in the clinic (the interview lasts on average 1 h). (2) School observation of the primary school child to assess for core symptoms of ADHD. This observation is usually carried out by the ADHD nurse specialist, using a structured form. The process includes observation of the child in the playground to observe social interaction with peers, observation of the child during lessons to check for impulsive and inattentive behaviours as well as overactivity, and a review of the child's completed class work. (3) Review of the screening questionnaires (P4) sent to home and school. Screening questionnaires are usually sent to the different subject teachers for the secondary school child.In the specialist ADHD clinic in East and North Hertfordshire, UK, assessment is by use of the P4 screening questionnaire, which is a 33-item screening questionnaire based on the After the conclusion of the diagnostic assessment by the paediatrician, the child psychiatrist, or both, a discussion is held with the parents and the young patient about the diagnosis and the different types of management options available. Information on where to access further parenting courses in managing the child's behaviour and psychoeducational materials are made available. When pharmacological therapy is recommended, the various types of medication available and their risks and benefits are discussed, and it is general practice to make this as visual as possible for the child and his/her parents by showing them dummy tablets of the proposed medication. Each of the child's difficulties is considered, to evaluate areas of particular concern. It is worth noting that the majority of parents accept pharmacological treatment for their children when indicated, although it is worth spending some time explaining how the medication works and allowing them to ask any questions they might have. Families also have further access to the ADHD nurse who sees the families after the initial clinic appointment and who discusses further questions that families may have and provides information on additional resources needed. Consent is usually obtained from the families to contact the school, and information on managing ADHD within the school is also forwarded to the class teacher.In primary school children, who carry out most of their schoolwork in school with little requirement for homework after school, preparations such as MPH-MR 30:70 are very useful. The child feels better as all the medication is taken at home before leaving for school and there is a lower risk of poor compliance, as parents ensure the child takes the medication. In addition, there is a lower risk of stigmatisation in school.pro forma that is used to review the core symptoms of ADHD and side effects of medication (in children treated with medication). The instrument also captures information on progress with learning and any emotional concerns. A summary of discussions with the family is maintained, including an action plan and plan for reviews.The ADHD nurse specialist is a key team member in the East and North Hertfordshire ADHD service. This nurse will usually follow-up, by telephone, with the family, 1-2 weeks after the medication regimen has started in order to assess the child's response to the medication, and to start titration to the therapeutic dose. All follow-up visits use a structured pro forma described above is used during all follow-up visits, including telephone consultations.Children started on medication are usually seen in the clinic after 1 month, and the optimal dose is determined. They are subsequently followed up on a 6-monthly basis if their symptoms are stable, and their height, weight and blood pressure are monitored; this is sometimes performed by the ADHD nurse specialist in the nurse-led clinic. Parents are instructed to contact the ADHD team  if they have any concerns that require an earlier review. Side effects are usually transient and tend to subside. Children treated for ADHD with more complex issues, who have poor tolerance to medication or who experience side effects are usually seen more frequently, and follow-up varies from monthly to 3-monthly. There is flexibility within the service to see children earlier if the need arises. The structured It is useful to have an up-to-date progress report from the school for the follow-up visits. This helps to monitor progress on the core symptoms of ADHD and also to find out about school, home and sibling progress. Where there is a lack of response to the medication, it is advisable to explore possible reasons through a discussion with the child, rather than stop treatment abruptly.Children who are stable on the 8-h preparation of MPH-MR 30:70 can be prescribed an additional MPH-IR dose in the evening when they make the transition to secondary school. This prevents changing the preparation to an entirely different one, particularly when it has been well tolerated, and extends symptom control to allow management of homework or other after-school activities.The majority of children respond well to long-acting MPH, although a few patients show appetite suppression and other side effects such as emotional concerns, anxiety, mood changes and tics. In some cases, temporary withdrawal of long-acting MPH may be necessary to see if the side effects subside.To manage poor weight gain, children may receive additional calories in the form of milk shakes or additional foods recommended by dieticians. With the 8-h MPH preparation there is usually a catch-up period in the evenings, when the medication effect wears off and children eat normally. Children are usually advised to eat a substantial breakfast before taking their medication and most are able to eat a healthy portion of food in the evening.Children with reduced height velocity may need to discontinue the medication temporarily if their height velocity continues to drop. As mentioned above, referral to a paediatric endocrinologist will determine whether there is an underlying growth problem.Headaches and abdominal pain usually improve after the first week of treatment; however, if they persist, analgesia can be given to relieve the symptoms. Emotional lability also usually improves with time; if it persists, the dose of the medication should be reviewed.Patient 1, age 14 years, presented with behavioural difficulties at home and school, and was first seen by clinicians following referral to the ADHD clinic at the age of 10 years. Concerns raised included challenging behaviour, impulsive behaviour, hyperactivity and fidgeting. Patient 1 lashed out very easily and struggled to calm down when he had an outburst; he had many outbursts at school, which made his peers wary of him, and was worried about his social skills.Patient 1 had some initial risk factors. He was born following a full-term pregnancy, weighed 3.5 kg and was in the special care baby unit for 2 days as a result of low blood sugar. He was the second child born to his mother. There was a history of domestic violence from patient 1's father, and his mother also had a history of psychiatric illness. Patient 1 had normal motor development milestones, but his speech and language development were delayed, and he also suffered from sleep difficulties.Patient 1 was diagnosed with ADHD at age 6.5 years in a different county but had not been treated with medication. Patient 1 and his mother then relocated to a different county and a further review of his symptoms was requested following increasing concerns regarding his behaviour at home and at school. The assessments consisted of a diagnostic interview by clinicians and a screening of the information received from home and the school. It was confirmed that patient 1 had ADHD combined type.Patient 1 started treatment with MPH-OROS, but significant symptom control was not achieved; his dosage was steadily titrated up to the maximum recommended dose of MPH-OROS (72 mg) but he felt that the medication effect wore off easily and also affected his appetite. Patient 1's medication was subsequently changed to 50 mg/day MPH-MR 30:70, and then titrated up to 60 mg/day, which he tolerated better than MPH-OROS. He made significant improvements: his concentration and his school grades improved . Patient 1's weight, height and blood pressure were normal for his age.Patient 1 is now making good progress in school and is generally happier, as confirmed by school reports, parental reports of school progress and by the medication monitoring document. He has also been able to form friendships. He is being followed up every 6 months in the ADHD clinic.Patient 2 was referred at age 5.5 years, following review in a child development centre, for concerns relating to poor concentration, impulsive behaviour and poor interaction in school. Patient 2's difficulties first became apparent when she was in preschool, where she required one-to-one support. She had problems with balance and motor skills, and walked with her feet turned in. She also had sleep difficulties and was very restless during sleep. At nursery, she had been functioning at an average level. Patient 2's behaviour had a significant impact on the whole family; she had defiant and attention-seeking behaviours.Patient 2 was born 1 week after her due date of birth; there were no concerns following her birth and she had been in good health. There was a family history of psychiatric illness in her mother's grandfather, as well as a history of hyperactivity and defiant behaviours in patient 2's cousin. Patient 2's clinical examination showed joint laxity but her neurological examination was normal.Patient 2 had a diagnostic assessment for ADHD and was found to have very high scores for inattention, hyperactivity and impulsivity, leading to a diagnosis of ADHD combined type with comorbid oppositional defiant disorder. ADHD management was discussed with the family, and her parents' decision was to try behavioural strategies at home and at school, and review patient 2's behaviour and progress in 1 year.At 1 year later, her sleep problems had worsened; she was started on melatonin to help with her sleep, which improved slightly, but continued to have significant ADHD symptoms that had an impact on her learning. Patient 2 was started on MPH-MR 30:70 10 mg to help control ADHD symptoms during the school day and her dose was gradually titrated to 30 mg once daily. Patient 2's ADHD and comorbid symptoms improved, including her concentration, her play and social skills, her relationship with friends, parents and sibling, and her sleep difficulties. Her dyspraxia and motor difficulties also improved.Patient 2 has made good progress on MPH-MR 30:70 30 mg and has had no side effects; she continues to have 2 mg of melatonin at night to improve her sleep pattern. She is being followed up on a 6-month basis.Patient 3, age 10 years, was referred at age 8 years with significant concerns about her behaviour in school. She was very talkative in class, fidgety and disruptive.Patient 3 was born following a normal pregnancy and had no problems after birth. She was an only child and was brought up following a very strict routine. Her developmental milestones were advanced, and she had many falls and emergency-room visits in the first few years of life. She also struggled significantly with learning and was found to have dyslexia. Although her dyslexia was well supported, she struggled continuously with her concentration; she frequently got into trouble in school and this caused significant difficulties for her parents, whose work life was constantly disrupted by calls from the school.Patient 3's parents had her referred for further assessment for ADHD. The positive and problem profile questionnaire (similar to the strengths and difficulties questionnaire) was sent to her parents and the school, and school observation was arranged by the ADHD nurse specialist. Patient 3 showed borderline scores for all the core symptoms of ADHD.Patient 3 was initially started on MPH-IR, 10 mg twice daily, following her parents' request for a short-acting preparation, to help them monitor her response during medication titration. The effect of the medication wore off quickly so her symptoms were not fully controlled. Her medication was then switched to MPH-MR 30:70, 30 mg once daily, to which she responded better. Patient 3 was satisfied with the once-daily dosage of MPH-MR 30:70 as she did not need to take medication in school and be different from her peers. Patient 3's relationship with her peers improved, and although she had slight appetite suppression whilst on the medication, she was able to have a normal evening meal with her family when she got back home, after the medication effect wore off.Patient 3 has made good progress on MPH-MR 30:70 and her symptoms are well controlled during the school day. She is due to start secondary school education and the plan is for patient 3 to continue taking MPH-MR 30:70 for the school day, with the option to add an MPH-IR preparation for the late afternoon when she is required to concentrate on homework. Patient 3 is satisfied with continuing the medication in secondary school.Patient 4, age 10 years, had a long history of poor concentration, and defiant and challenging behaviour. She was born following a normal pregnancy and delivery, and had a history of delay in all areas of her development; she walked late, talked late (age 3) and found mainstream schooling very challenging.Patient 4's parents separated when she was 4 years old, and a shared contact arrangement with both parents was agreed. After the separation of her parents, patient 4's behaviour became increasingly challenging. She found it difficult to settle in mainstream school and made little progress in her learning; she was, therefore, transferred to a special school for children with moderate learning disabilities. Patient 4's behaviour continued to deteriorate in the special school. She was very impulsive, defiant and constantly fidgety; she lashed out frequently at teachers and other children, and had a very poor concentration span. She had a structured behavioural management plan in school as well as a period of monitoring. However, although her behaviour improved slightly, she made no progress in her learning, as reflected by her poor school grades and her teachers' reports, and she continued to have problems with concentration and constant fidgeting.Patient 4 was assessed for ADHD and her symptoms met the diagnostic criteria for ADHD with comorbid oppositional defiant disorder. She was started on a low dose of MPH-IR and showed a slight improvement but had significant rebound symptoms and several emotional side effects. She was moody, very tearful and her behaviour was of concern at home and at school. Her medication was then changed to MPH-MR using MPH-MR 30:70. She showed a slight improvement for a few weeks at a dose of 20 mg/day but had significant problems with poor appetite and poor sleeping patterns; according to her parents, she was also more aggressive on MPH-MR 30:70. The dose was reduced to 10 mg without any appreciable reduction of side effects. As she did not tolerate even small doses of MPH, MPH-MR 30:70 was discontinued and clonidine , a non-stimulant preparation, was started to help with ADHD symptoms. Although clonidine is not currently approved in ADHD, evidence suggests it may have some benefit . After 1Patient 4 had all medication discontinued, and a period of monitoring was carried out with more behavioural support and one-to-one management. She continued to struggle with poor attention and concentration, showed a lack of progress with learning and exhibited high levels of anxiety. A meeting of health, education and social services professionals was held to address patient 4's needs. She was reassessed by the doctor and diagnosed with ADHD, comorbid oppositional defiant disorder and additional comorbidities, such as anxiety symptoms and learning difficulties. She was also assessed for autistic spectrum disorder but did not meet the diagnostic criteria.Patient 4 was trialled on atomoxetine and given access to a nurse support service for patients on this medication, run by an independent provider. She was started on 10 mg once daily for 2 weeks, titrated to 18 mg once daily for 2 weeks, and then maintained on 25 mg once daily thereafter. Titration was performed slowly, with close monitoring. Patient 4 showed a significant response to atomoxetine: her core ADHD symptoms improved, she was less anxious and her appetite and sleep improved. She still has some residual symptoms of impulsivity but, overall, she has made progress through a combination of atomoxetine and behavioural strategies.The early identification of ADHD symptoms in children is essential to prevent the complications that arise from late diagnosis. Children with risk factors for ADHD  -41 need Treatment with MPH-MR 30:70 prevents disruption in the child's school day programme by removing the need for a lunchtime medication dose administered in school. Parents who have doubts about medication treatment and concerns about the child taking medication in school are more likely to accept treatment with a flexible once-a-day preparation such as MPH-MR 30:70.Children treated with MPH-MR 30:70 can have problems with appetite suppression, but as the effect wears off in the evening, the child is usually able to eat a normal evening meal, which prevents weight loss in most children.Some children with learning difficulties and ADHD can have a poorer response to MPH compared with children without comorbidities. In these cases, the side effects of MPH-MR 30:70 can be seen with very small doses of MPH. Children with poor response to MPH-MR 30:70 and other MPH preparations should have their symptoms re-evaluated to rule out comorbidities such as anxiety disorder and autistic spectrum disorder, which may account for the poor response.Providing adequate support for children treated with MPH-MR 30:70 is essential to ensure compliance with treatment.Formal consent has been obtained by the Author for all cases reported in the article.Support was received from Shire Pharmaceuticals Ltd to attend conferences.IT is the lead paediatrician for ADHD services in East Hertfordshire, UK, where she runs a weekly joint ADHD clinic with the Child and Adolescent psychiatrist and works within an ADHD specialist team. IT also sees children with other neurodisability issues who may have comorbid ADHD, where the presentation may be more complex and challenging to manage. IT has vast experience in managing children with complex ADHD. She has 18 years of experience in paediatrics and also has extensive experience in the use of psychopharmacologic agents in managing children with ADHD.