Racial disparities persist in adverse perinatal outcomes such as preterm birth, low birthweight (LBW), and infant mortality across the U.S. Although pervasive, these disparities are not universal. Some communities have experienced significant improvements in black (or African American) birth outcomes, both in absolute rates and in rate ratios relative to whites. This study assessed county-level progress on trends in black and white LBW rates as an indicator of progress toward more equal birth outcomes for black infants. County-level LBW data were obtained from the 2003 to 2013 U.S. Natality files. Black LBW rates, black-white rate ratios and percent differences over time were calculated. Trend lines were first assessed for significant differences in slope . For counties with parallel trend lines, intercepts were tested for statistically significant differences . To assess progress, black LBW rates were compared to white LBW rates, and the trend lines were tested for significant decline. Each county’s progress toward black-white equality was ultimately categorized into five possible trend patterns (n = 408): (1) converging LBW rates with reductions in the black LBW rate ; (2) converging LBW rates due to worsening white LBW rates ; (3) diverging LBW rates ; (4) parallel LBW rates ; and (5) overlapping trend lines . Only four counties demonstrated improvement toward equality with decreasing black LBW rates. There is significant county-level variation in progress toward racial equality in adverse birth outcomes such as low birthweight. Still, some communities are demonstrating that more equitable outcomes are possible. Further research is needed in these positive exemplar communities to identify what works in accelerating progress toward more equal birth outcomes. Worldwide, low birth weight contributes to 60–80% of all neonatal deaths  and is aOne of the strongest predictors of infant mortality is LBW, a category which can include both premature babies and those who are small for gestational age. Infants who are LBW weigh 2,500 grams (5.5 pounds) or less at birth, while very low birthweight (VLBW) infants weigh 1,500 grams (3.25 pounds) or less at birth . VLBW inWhile much of the literature on perinatal outcomes reinforces the theme that racial disparities are pervasive and persistent, Fry-Johnson and colleagues have demonstrated that disparities in infant mortality are not inevitable and that there are counties with more equitable birth outcomes . Recent Therefore, we conducted this study to assess trends in county-level black-white disparities in LBW rates, in order to identify counties with trend lines demonstrating progress toward more equitable outcomes. Positive progress at the county-level would be demonstrated by improvement in outcomes  with concomitant improvement in relative disparities . Such positive progress in even a small proportion of counties would demonstrate the real possibility of eliminating racial disparities in LBW rates and achieving both optimal and equitable outcomes for all babies, regardless of race.County-level LBW data were obtained from the 2003 to 2013 U.S. natality files. Data were obtained with approval from the National Association for Public Health Statistics and Information Systems through the all-county data files for counties with populations of 100,000 or greater. After selecting counties with at least 10 LBW babies in each racial group by year to protect confidentiality, 408 counties from 50 states and the District of Columbia were eligible for study inclusion, with data restricted to live births for whom race was categorized as non-Hispanic white or black. While this number represents only 13% of US counties, these counties include approximately 85% of all the black births in this country on average for each year included in the analysis. Data were deidentified before receipt by the authors, and this study was approved by the Florida State University Institutional Review Board.when a county’s rates are converging, they cannot tell you how a county’s rates are converging. That is, they cannot distinguish between whether a county’s rates are converging because the black rate is declining or because the white rate is increasing.In order to determine how disparities are changing over time, we modeled separately for each year the county-level incidence rate of LBW babies for all black births and all white births. We chose to model incidence rates as opposed to rate ratios because, while rate ratios can tell you Based on the work of Rust et al ,16, we i1) Persistent disparities ;2) Sustained equality ;3) Convergent ; and4) Divergent .Each county’s black LBW rate and white LBW rate from 2003–2013 were calculated annually. These rates determined if, and to what extent, counties made progress towards equal  levels of LBW rates.p-value thresholds to reduce the probability of a Type I error. Accordingly, all hypothesis tests were two-tailed and conducted at the 0.005 level [We conducted a log-linear model using OLS regression with race represented as a dummy variable for black rates, year included as a linear trend, and with each county modeled separately via a full set of county-specific dummies and corresponding county-specific interaction terms. This specification estimated the trend patterns for all counties by race across the 11-year study period. For this model, the county-specific time by race interaction served as the main independent variable, and the log of the low birthweight rate for each race was the dependent variable. The analysts generated the code for the analysis using SAS software, version 9.4. Based on the model results, counties were then categorized by trend pattern. A convergent trend pattern was identified when the estimated slope for the black rate was statistically significantly negative, the estimated slope for the white rate was statistically flat, and the difference between the two rates (the coefficient on the interaction term) was statistically significantly negative. A divergent trend pattern was identified when the estimated slope for the black rate was flat or statistically significantly positive, the estimated slope for the white rate was statistically significantly negative or flat, and the difference between the two rates was statistically significantly positive. Sustained equality and persistent disparity were identified when the difference between the two rates was statistically indistinguishable, with sustained equality determined when the difference between the intercepts was not statistically significant and persistent disparity determined when the difference in intercepts was statistically significant and positive for the black rate. Recent discussions on multiple hypothesis testing have emphasized the need to adjust 05 level .After these classifications were made, more detailed information  was compiled for counties demonstrating positive progress with convergent trend patterns and concomitant reductions in black LBW rates. A graph of aggregated data for all counties in this trend pattern category based on the black and white LBW rates from 2003 to 2013 was also produced. This graph provides a visual representation of the convergence trend to better understand the counties that are achieving progress towards equality in black and white LBW rates.We also projected the total potential number of low birthweight births averted if we had eliminated the gap in black-white LBW rates in all included counties during the study period. This was conducted by setting the white LBW rate as a function of the black total births and LBW births per year per county for a cumulative total. That is, for each year and county, the following calculation was made: Potential averted black LBW births = Total number black LBW births–.Additionally, the potential number of LBW births averted for all counties during the study period were black-white LBW rates to be equal was calculated to be 371,176. According to the most conservative estimate, an average LBW hospitalization stay in 2001 was estimated at $15,100. If we applied this to the study period, $5,604,757,600 in immediate hospitalization costs could have been avoided had black-white equality in LBW rates been achieved ,19. It iThe purpose of this study was to better understand county-level black-white disparities in LBW rates, with the goal of identifying counties demonstrating progress toward equal outcomes. Our main finding is that not only is there significant U.S. county-level variation in both black and white LBW rates, but that there is also evidence of meaningful progress in specific counties.The slow progress in achieving reductions in racial disparities in LBW rates has already been well documented at a national level, but the local-area variation provides a more nuanced picture. The four counties moving toward equitable outcomes reinforce the growing body of evidence that racial disparities in health outcomes are not inevitable ,20. FromWe chose to examine all categories of LBW infants given their increased vulnerability for poor short- and long-term health outcomes, across a continuum of risk from extreme VLBW to mild LBW. While VLBW births are especially important given their correlation with infant mortality rates, especially in the black population, they are a subset of the larger problem of LBW births . IntervePrevious literature suggests that different risk factors and stressors may be associated with LBW outcomes in different racial groups. Black women who had a LBW infant were more likely to be of low socioeconomic status than white women, despite also being more likely to be in good health . HoweverAcross racial groups, neighborhood-level social determinants and individual psychosocial stressors can be difficult to tease apart as risk factors for LBW or very preterm birth. Data from the Early Childhood Longitudinal Study Birth Cohort linked to county-level neighborhood disadvantage index demonstrated that across all neighborhood strata, but especially within the most disadvantaged neighborhoods, LBW risk was exacerbated by the experience of stressful life events before conception . El-SayeChronic stress has been shown to be notably higher in the daily lived experiences of black women compared to whites ,27, and Although childhood poverty may have long-lasting and even epigenetic effects on women as they enter childbearing years, data on 2,463 women from 52 clinics in five Michigan communities suggests that upward mobility (moving from low-SES to middle or upper-class SES) could be significantly protective of fetal growth, as measured by the birth outcome of small for gestational age . Upward Structural equation modeling of preconception processes influencing birthweight using data from 1,580 mother-daughter pairs in National Longitudinal Survey of Youth found that birthweight was shaped not only by factors in women’s early background , but also by conditions dating back as much as three generations . Two othData on 3,869 women from the 1998–2000 Fragile Families and Child Wellbeing Study showed significant associations between known social and behavioral stressors  and low birthweight, but did not fully explain the racial disparities in LBW . AnalysiGeographically granular analysis at the census tract and neighborhood levels in New York City found a positive association between residential segregation and low birthweight, after controlling for individual-level risk factors and neighborhood poverty . ResidenSeeking to tease out the differential effects of individual and neighborhood-level factors, Vang and Elo examined the association between neighborhood minority diversity and infant birthweight, among black non-Hispanic women stratified by country of birth (U.S. born vs. foreign born). Black women born in Africa or the Caribbean had significantly higher birthweights than did U.S.-born black women, even after controlling for neighborhood deprivation, residential instability, individual-level sociodemographics, maternal health behaviors, and gestational age. Neighborhood non-white racial-ethnic diversity (minority heterogeneity) at the census tract level had a positive association with higher black infant birthweights, as did living in a majority-minority neighborhood . Moving The trend of increasing LBW rates among white mothers in some counties also merits attention. Factors driving increases in white LBW rates in pockets of the country might include the impact of the economic downturn, increasing rates of opioid use and addiction, variable access to prenatal care, variation in smoking rates (including youth adoption of e-cigarettes), and other biopsychosocial stressors. Further study is needed to understand specific drivers of increasing white LBW rates in these counties.Interventions to decrease prematurity and LBW births could be both obstetrical and social-contextual. For example, one survey at the hospital level demonstrated that LBW infants born in high-black (patient-mix) hospitals had more severe levels of nurse understaffing and higher rates of infection and infant discharge without breast milk than low-black hospitals . ReducinInterventions to improve these birth outcomes, especially in minority communities, often focus only on a single risk factor, even when evidence strongly suggests multifactorial etiologies. For example, pilot studies demonstrate the ability to increase maternal knowledge about health literacy and preterm birth but show no proven impact on birth outcomes . SpecifiA growing number of multi-dimensional, place-based efforts to address racism are emerging and may further illuminate the paths by which communities may achieve maternal-child health equity . For exaAdditionally, further research is needed on formal and informal policies impacting health systems and community-level factors that improve care and support of women before, during, and after conception, as well as the broader upstream social and economic context and built environment in which people live .This study is subject to all the known limitations of vital statistics data and, specifically, the designation of race and ethnicity on birth certificates. The lack of inclusion of paternal race-ethnicity is another relevant factor emphasized by Fulda et al . Our stuLBW is a significant driver of the black-white gap in birth outcomes and in the resultant impact on child health and development over the life course. It is thus an appropriate target for achieving greater racial equality in birth outcomes. Progress has been slow at the national level. Local-area variation, and especially the ability of some counties to make progress in reducing black LBW rates and the black-white disparity, suggests that there are paths for other counties to follow in achieving more optimal and equitable birth outcomes for everyone. Further research is needed to understand what is working in positive exemplar counties and to test multi-dimensional interventions for improving birth outcome equity in high-disparity locales.


Background: Early assessment and intervention are crucial to alleviate symptoms and prevent long-term negative outcomes in children suffering from Attention-deficit/hyperactivity disorder (ADHD). In Germany, at present, no standardized screening for ADHD is routinely administered. This study aims to evaluate a potential screening measure in a study population that is representative for a primary school entrance exam population in a German metropolitan region.Methods: Based on various socio-demographic variables, a sample of n = 500 5-year-old children , representative of a primary school entrance exam population from a German metropolitan region, was selected. Their parents completed a written survey consisting of the CBCL and a brief screening tool for ADHD symptomatology based on the DISYPS-II questionnaire. Demographic data were also collected.Results: The subscale “Attention problems” of the CBCL/4-18 showed results in the clinical range for n = 10 (2%) participants. The ADHD screening identified n = 23 (4.6%) participants as suspect of having ADHD with a statistically significant gender difference . In n = 5 (1%) participants, all boys, both CBCL/4-18 and the ADHD screening were indicative of ADHD.Conclusions: Results indicate that screening for ADHD in this population may be both feasible and reasonable given the high prevalence and chronic nature of this disorder and the benefit of an early initiation of treatment. Results match previously reported figures for prevalence of ADHD-related symptoms and gender differences in preschool and older pediatric populations and thus do not support the hypothesis that the prevalence of ADHD in a metropolitan region is significantly higher than in other regions. Attention-deficit/hyperactivity disorder (ADHD) is characterized by impulsivity, hyperactivity and inattention . It is oRegarding early assessment of ADHD, useful and valid screening tools should be available and routinely administered to children, ideally at the primary school entrance level. The main objective of this study is to evaluate such a measure in a study population that is representative for a real-world primary school entrance exam population in a German metropolitan region. In Germany, at present, no such standardized screening for ADHD is routinely administered.Parents of 5-year-old preschool children from the German metropolitan region Hamburg were asked to complete a written survey. Five hundred families were selected based on the following socio-demographic variables in order to generate a sample representative of this metropolitan region: number of children, mother's marital status, mother's, and father's work status and position. Identification and selection of parents and participants as well as conduction of the written survey were performed by a private survey institute and financially supported by Lilly Deutschland GmbH . Inclusion criteria were: 5;0–5;11 years of age at the time of survey, sufficient level of understanding of the nature and the content of the study by parents, general agreement to potentially be invited to a personal examination by one of our research team's child and adolescent psychiatrists and to be asked to complete a follow-up survey at a later time. Main exclusion criteria were: serious unstable illnesses, non-agreement to further investigation, and previous treatment for ADHD. The latter was chosen in line with previous, similar studies  and in oT score < 67), borderline (T 67–70), or clinical range (T score >70). For this study in preschool children, two items were changed to address behavior at kindergarten rather than at school (items 23 and 30). Additionally, two items regarding school were dismissed (items 61 and 101) resulting in a number of total items of 116.The CBCL/4-18 is a questionnaire for parents of children aged 4–18 years acquiring information on competencies and problems of children  and has A short and easy to complete questionnaire asking parents about core symptomatology of ADHD within and outside of the home/family setting was used for this study . This soFurther information to be collected from the participants was, among others, data on previous and current treatments and medications and various demographic data.n = 5 for several items. P-values reported are two-sided. P-values of 0.05 or less were deemed statistically significant. Data were collected in Microsoft® Office Excel. All analyses were performed with IBM® SPSS® Statistics Version 22.Demographics were summarized descriptively using participant count and percentages of the total population. Furthermore, demographic variables  were compared using Fisher's exact tests as participant counts were to be expected lower than n = 260 boys (52%) and n = 240 girls (48%), all between 5;0 and 5;11 years old and selected in order to create a representative sample, took part in this study. The questionnaire was completed by mothers in n = 450 (90%), by fathers in n = 41 (8.2%), and by other family members in n = 9 (1.8%) of cases.Parents of n = 1 (0.2%) participant was treated by a child and adolescent psychiatrist, n = 8 (1.6%) by a psychologist. Parents reported that their children had been treated because of mental or conduct problems in the past (>6 months ago) in n = 16 (3.2%), and recently or currently in n = 31 (6.2%) cases. None of the participants received psychotropic medication  at the time of survey. No statistically significant gender differences were found for all characteristics describing the study population  cases. The other subscales showed the following results, sorted from highest to lowest percentage: aggressive behavior , rule-breaking behavior , anxious/depressed , thought problems , social problems , somatic complaints , withdrawn . Statistically significant gender differences were not present in any of the CBCL scores. For a full depiction of CBCL/4-18 results, see Table Most relevant for the aim of this study, the subscale “Attention problems” of the CBCL/4-18 showed results in the clinical range for n = 10 % cases. n = 23 (4.6%) participants were suspect of having ADHD. This group consisted of n = 17 (6.5%) boys and n = 6 (2.5%) girls. This gender difference was statistically significant .According to the cut-off described in the methods section, n = 5 (1%) of the children, which were all boys, both CBCL/4-18 and the ADHD screening were indicative of ADHD .For HD Table . Yet, thn = 3,501 children (5–7 years old) found a prevalence of problems of hyperactivity/inattention in 0.7% with a gender ration boys vs. girls of 2:1 , 4.6% (ADHD screening), and 1% (CBCL and ADHD screening combined). Prevalence rates between 2% and 9.6% have previously been reported for ADHD in preschool children –25. For s of 2:1 . These rWhile data on preschool children is limited, evidence for the prevalence of ADHD in school-age children around 5% is extensive , 4. DepeIt is important to note that the questionnaires used in this study cannot provide or be a substitute for a full child and adolescent psychiatric diagnostic assessment. Yet, for purposes of a routine screening of preschool children the “ADHD sheet” used in this study may be useful as it can easily and quickly be administered, yet follows the diagnostic criteria of ICD-10. Taking into account the relatively high prevalence of ADHD, its probable impairments and the fact that symptoms might not be apparent in a routine physical exam (in contrast to other disorders such as autism), a screening for ADHD could prove useful. If a child was screened positive and thus ADHD may be present, a full diagnostic workup could be performed by a child psychiatrist in a second step. Such a process could identify children with ADHD more reliably before symptoms and/or development of comorbidities may lead to severe negative outcomes, and could allow for adequate treatment. For this reason it would also prove to be cost-effective by avoiding later healthcare and social welfare cost. Nevertheless, these positive aspects must be carefully weighed against the potential negative effects related to a general screening for 5-year-old children. Most importantly, a screening would also result in false positive and false negative cases. For false positive cases, the result of the screening could prove stressful for the parents and families affected, and may cause them to see their children in a “new light”. It may appear to the parents that their child has more problems than before and this could be a negative factor for the children's healthy development. False negative cases would not benefit from the screening.A diagnostic assessment for ADHD at the school entry age needs to be performed very carefully considering the developmental stage of each individual child. This is especially important in the population of preschool children, which shows a physiologically wide distribution for attention abilities, impulsivity, and hyperactivity. Further studies could further investigate whether the positive effects of routinely performed early screening for ADHD exceeds its potential negative effects.Since this study investigated screening measures and did not include a full diagnostic assessment, the actual prevalence of ADHD in the study popoulation might be even lower. Consequently, these results are not in support of the hypothesis that the prevalence of ADHD in a metropolitan region is significantly higher than in other regions. If this were the case and environmental factors in a metropolitan region did cause a higher prevalence, one would expect much higher rates of children suspect of having ADHD in this study. Additionally, this set of data seems to further substantiate previous research suggesting that ADHD prevalence is rather robust across geographical regions , 31, 32.n = 5 boys and no girl being suspect of having ADHD. This gender difference may seem obvious, yet did not reach statistical significance . The gender difference, when using the results of the ADHD screening instrument only, was statistically significant .CBCL/4-18, by its design, does not specifically assess ADHD symptomatology. Thus, for this study the subscale “Attention Problems” was used as an estimate in combination with the ADHD-specific screening instrument. The combination of data from both instruments led to more refined results with This study was designed to reflect the real world setting as all participants and parents agreed to be possibly invited to a personal examination by one of our research team's child and adolescent psychiatrists and also to be asked to complete a follow-up survey some years after the initial survey. It is planned to perform, analyze and publish a comprehensive clinical investigation of a subgroup identified as suspect of having ADHD in the future.Regarding early intervention and following the model of gene-environment interaction, the question arises whether environmental factors could be influenced early on to benefit children with a genetic predisposition to develop ADHD. Children growing up in urban areas are exposed to very different environmental conditions than those in rural areas. They may be exposed to more potentially harmful agents from pollution, to a higher number of psychosocial stressors, play less outdoors in natural environments, and consequently may consume more electronic media –36. The This study has several limitations. First, children/families with an earlier ADHD diagnosis or respective treatment were intentionally excluded from this study (cf. Methods). This limits comparability with earlier reported rates from studies investigating prevalence of ADHD. Yet, prevalence of ADHD has previously been investigated elsewhere and was not the focus of this study. Main focus was rather the evaluation of a screening measure which is most adequately done in a sample population without a portion of subjects who have already undergone a diagnostic workup and therapeutic interventions for the disorder in question. This reflects a real-world situation where a child with a diagnosis and treatment of ADHD would not be screened for ADHD. Second, a selection bias may have occurred. A general and widespread problem in clinical research, only willing and interested parents may have participated. Though relatively small, the financial reimbursement may also have acted as an additional incentive to participate. This might have led to a non-representative sample. Yet, in this study, a large sample was recruited and social and demographic variables were taken into account for the final selection of participants in order to create a representative sample. Third, the data relied on parent report, solely. Although the confidential nature of the survey was clearly communicated to the parents, it remains possible that some did not honestly complete all questions due to response bias. In order to eliminate this limitation, a follow-up clinical examination of a subgroup of participants by a child and adolescent psychiatrist is currently under way. Fourth, the instruments applied fulfill only a screening purpose and therefore show clear limitations regarding the diagnostic validity of their results. Fifth, interpretation of these results mandates caution due to the young age of participants and a possible overlap of relevant symptoms with physiological developmental phenomena. Sixth, the families participating in this study were selected from a large database of families by the private survey institute according to the inclusion criteria described above. Unfortunately, the latter was not able to provide the authors with exact figures on how many families did not accept the invitation to participate or were excluded. This data is consequently missing in the analysis and discussion of this study.These results from a large sample representative of a primary school entrance exam population in a German metropolitan region indicate that screening for ADHD in this population may be both reasonable and feasible given the high prevalence and chronic nature of this disorder and the benefit of an early initiation of adequate treatment. Furthermore, the results match previously reported figures for prevalence of ADHD-related symptoms and gender differences in preschool and older pediatric populations. Considering the limitations of this study, results do not support a hypothesis that the prevalence of ADHD in a metropolitan region is significantly higher than in other regions. A comprehensive clinical investigation of a subgroup of children identified as suspect of having ADHD has been planned to be performed, analyzed, and published in the future.KM performed the statistical analysis, interpreted the data, wrote the manuscript with AH, and approved the final manuscript as submitted. TK conceptualized and designed the study, collected and interpreted the data, critically reviewed the manuscript, and approved the final manuscript as submitted. ML interpreted the data and provided substantial clinical and statistical input, critically reviewed the manuscript, and approved the final manuscript as submitted. RD conceptualized and designed the study, interpreted the data and provided substantial clinical and statistical input, critically reviewed the manuscript, and approved the final manuscript as submitted. AH interpreted the data and provided substantial clinical and statistical input, wrote the manuscript with KM, and approved the final manuscript as submitted.KM has served as investigator in clinical trials conducted by Lundbeck, Shire, Sunovion and Teva, plus in EU FP7 programme and Horizon 2020 funded projects. TK reports no potential conflicts of interest. ML has served as investigator in clinical trials conducted by Lundbeck plus in EU FP7 programme funded projects. RD has received compensation for serving as consultant or speaker, or he or the institution he works for have received research support or royalties from the organizations or companies indicated: EU (FP7 Programme), US National Institute of Mental Health (NIMH), German Federal Ministry of Health/Regulatory Agency (BMG/BfArM), German Federal Ministry of Education and Research (BMBF), German Research Foundation (DFG), Volkswagen Foundation; Boehringer Ingelheim, Ferring, Janssen-Cilag, Lilly, Lundbeck, Otsuka, Servier, Shire, Sunovion/Takeda and Theravance. Dr. Dittmann owns Eli Lilly stock. AH has served as investigator in clinical trials conducted by Janssen-Cilag, Otsuka, Shire, Lundbeck, Sunovion and Teva, plus in EU FP7 programme and Horizon 2020 funded projects. He has received conference travel support and compensation for serving as consultant or speaker by E. Lilly and Shire. The remaining 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.


P) hydrous-silicate melts has been investigated, little is known about solute enrichment and fractionation in UHP (>3.5–4 GPa) solute-rich aqueous fluids released along colder geothermal gradients. Here, we performed in situ LA-ICP-MS trace-element analyses on selected UHP prograde-to-peak fluid inclusions trapped in a kyanite-bearing quartzite from Sulu (China). The alkali-aluminosilicate-rich aqueous fluid released from the meta-sediments by dehydration reactions is enriched in LILE, U, Th, Sr, and REE. Inclusions trapped at increasing temperature (and pressure) preserve a gradual and selective trace-element enrichment resulting from the progressive dissolution of phengite and carbonate and the partial dissolution of allanite/monazite. We show that, at the investigated P-T conditions, aqueous fluids generated by dissolution of volatile-bearing minerals fractionate trace-element distinctly from hydrous-silicate melts, regardless of the source lithology. The orogenic/post-orogenic magmas generated in a mantle enriched by metasomatic processes involving either solute-rich aqueous fluids or hydrous-silicate melts released by the slab at UHP conditions can preserve evidence of the nature of these agents.The geochemical signature of magmas generated at convergent margins greatly depends on the nature of fluids and melts released during subduction. While major- and trace-elements transport capacity of ultrahigh pressure (UH Trace-element systematics based on experiments and natural rocks indicate that hydrous-silicate (HS) melts generated by high-pressure (HP) and ultrahigh-pressure (UHP) dehydration melting along high-temperature gradients are very efficient metasomatic agents, enriched in LILE, LREE, Th, U18 by at least one order of magnitude with respect to aqueous fluids released by sub-solidus dehydration reactions along low-temperature gradients25. At intermediate geothermal gradients, aqueous fluids are released at P and T near or just above the second critical end-point of the H2O–pelite and H2O–granite systems 27. At these conditions, fluids have physicochemical properties intermediate between aqueous fluids and hydrous-silicate melts, and their solute load increases dramatically even for small temperature rise by progressive mineral dissolution26. The only, semi-quantitative trace-element data from a natural UHP aqueous fluid released during deep subduction  show strong enrichment in LILE, LREE, Pb, Sr, U, and Th28, i.e. enrichments similar to that observed in fluids produced by experiments at P-T conditions above the second critical end-point of H2O–silica(te) systems30. Whereas some authors13 suggest that there are no significant differences in trace-element content and fractionation between aqueous fluids  and HS melts generated at similar temperature conditions, others30 argue that the UHP aqueous fluids have higher capacity than melts to mobilize LREE. The fluid evolution, as dissolution processes move forward, is also poorly constrained.Hydrous fluids and silicate melts-released by dehydration or melting of subducting slabs at sub-arc depthsP “alkali-aluminosilicate-rich aqueous fluid” (hereafter “aqueous fluid”) released from a meta-arenite subducted at P > 3.5 GPa along an intermediate P-T gradient. The composition was obtained by in situ Laser Ablation Inductively Coupled Plasma Mass Spectrometer (LA-ICP-MS) analyses on multiphase-solid inclusions trapped in kyanite during UHP prograde-to-peak evolution of a kyanite-bearing quartzite from Sulu (China).Here, we report the trace-element composition of a natural, UHP meta-sediments. Dissolution processes occurring in the investigated P-T range generate solute-rich aqueous fluids  with similar trace-element fractionations , regardless of the involved lithology. These fractionation patterns are distinct from those in HS melts produced by partial-melting processes. Potassic-ultrapotassic magmatism can preserve the trace-element fractionations of the subduction-related metasomatic agent, with implications on the geodynamics of convergent margins.This study allows characterizing, for the first time, the gradual and selective enrichment of trace elements in a natural aqueous fluid released by prograde-to-peak dissolution of phengite, carbonate and allanite/monazite from subducted UHP porphyroblastic kyanite of a kyanite-quartzite from Hushan . The Qinling-Dabie-Sulu orogen formed by Triassic subduction and collision of Yangtze craton beneath Sino-Korean craton. In southern Sulu terrane, the UHP Unit consists of orthogneiss with minor paragneiss, eclogite, amphibolite, ultramafic rocks, quartzite, and marble31. Peak metamorphic conditions, dated at 235–225 Ma32, are primarily estimated at T = 730–890 °C and P = 3.5–4.5 GPa34, although lower P-T conditions are also suggested (Supplementary Information). Weakly-foliated kyanite-quartzites occur within gneiss and consists of pre-kinematic MSI-rich porphyroblastic kyanite, grown from phengite during UHP prograde-to-peak path, retrograde syn-kinematic inclusion-free kyanite, and OH-rich topaz, muscovite, paragonite, and pyrophyllite. Rutile, zircon, pyrite, barite, monazite, and apatite are accessory minerals. The sample for fluid inclusion study (RPC547) was selected among those used to constrain metamorphic and fluid evolution of kyanite quartzites35 (Supplementary Information).Studied fluid inclusions occur as multiphase-solid inclusions (MSI’s) in UHP core and rim of porphyroblastic kyanite (Supplementary Information). Selected MSI’s have negative-crystal shapes and dimensions variable from 5 to 30 μm in length  data obtained by Fractionation patterns show systematic differences between MSI’s trapped in porphyroblastic kyanite core and those trapped in the rim. Whereas MSI’ in the inner core , slab dehydration reactions involving phengite in meta-sediments can release alkali-aluminosilicate-rich aqueous fluids from the slab. In agreement with previous studies35, UHP aqueous fluids could have been generated near the second critical end-point of the H2O-pelite system. Present data reveal that these fluids are extremely enriched in LILE, U, Th, Sr, and REE, but not in HFSE and that they progressively change the amount and fractionation of their trace-element budget during UHP prograde-to-peak P-T evolution.Our data on MSI’s indicate that, at the investigated 25 and thermodynamic models36, if dehydration reactions occur near or just above the second critical end-point of the H2O-silica(te) system, even a small change in T ± P ± pH can produce relevant variations in the amount and kind of solutes because the rock-forming minerals steadily dissolve in it due to their increasing solubility in water. Thus, both the nature of rock-forming minerals and their degree of dissolution are responsible for the gradual variations in trace-element content and fractionation. Considering the very simple UHP mineral assemblage of the studied lithology, the HFSE negative anomalies measured in MSI’s  can be compared with those of HS melts obtained at similar P-T conditions from experiments15  during dissolution or partial-melting processes at the considered P-T conditions. For example, rutile and zircon do not dissolve in UHP aqueous fluids, whereas they participate to melting at increasing temperature  fluid MSI7) is one order of magnitude higher than that in the experimental melts. Our work indicates that aqueous fluids released from meta-sediments along intermediate subduction gradients at pressures greater than 3.5 GPa can transport similar or even higher amounts of trace elements (in particular LREE) than HS melts generated from similar lithologies at UH is one o2O-pelite system27. The possibility to distinguish between these “supercritical” aqueous fluids and hydrous-silicate melts by their trace-element fractionations is still debated30. In Fig. P “supercritical” fluids and HS melts released from different lithologies  are plotted in a Th/La vs. Ta/La diagram. As evident, it seems to be a promising diagnostic diagram to identify the nature of a metasomatic agent released at the considered range of P-T conditions (700–900 °C and 2.2–4.5 GPa), regardless of the source lithology. At P-T conditions higher than those investigated, the complete incorporation of minerals in both aqueous fluids and HS melts makes these two metasomatic agents chemically indistinguishable from each other, including their trace-element content. It is noteworthy that this overlapping, observed in some experiments14, occurs at P-T conditions distinct from a lithology to another, since the P-T conditions of the second critical end-point depend on the considered chemical system.Aqueous fluids released at pressure above 3.5 GPa have likely attained conditions near or just above the second critical end-point of the HP-T conditions near or just above the second critical end-point the structure of the solutes changes from (hydrated) ions to monomers and higher polymers43. In particular, their viscosity is lower than that of HS melts, enhancing element-transport capacity from the source  into the surroundings 44. The presence of LREE and LILE-rich UHP veins containing quartz ± omphacite (or jadeite) ± kyanite ± allanite ± zoisite ± rutile ± garnet precipitated from supercritical fluids45 in the Chizhuangh eclogites (ca 30 km SSW of the sampled area) confirms the mobility of these fluids and their ability to transport elements out of source lithology.Supercritical fluids are considered more mobile than HS melts because at P “supercritical” fluids released from subducting sediments along an intermediate geothermal gradient can be efficient metasomatic agents as HS melts. It also shows that, regardless of the source lithology, “supercritical” fluids have distinct fractionation patterns for selected elements. The raising question is if the orogenic/post-orogenic magmatism generated by processes involving metasomatic addition to the source mantle wedge by “supercritical” fluids or HS melts7 could preserve evidence of the nature of the agent, with consequences on the geothermal gradient of their source and, hence, on the geodynamic evolution of the area . We discuss, as an example, the Th/La vs. La/Ta fractionation in Plio-Quaternary potassic-ultrapotassic magmas from the Roman and Tuscany Provinces . The Roman magmas are interpreted as generated by partial melting of a carbonate-amphibole-phlogopite-bearing mantle metasomatized by HS melts or supercritical fluids released by carbonate-silicic sediments along a cold subduction gradient46. In Fig. 47 are plotted in a Th/La vs. La/Ta diagram. Data for each volcanic complex are relatively gathered and distributed either along the fractionation trend defined by “supercritical” fluids (Colli Albani and Sabatini), or along that of HS melts (Vico and Vulsini). Such a distribution suggests that the metasomatic agent of the mantle source was a “supercritical” fluid, released at increasing temperature, that gradually changed its element fractionation to become indistinguishable from an HS melt. A similar evolution could fit with the progressive rise of isotherms at mantle depth by Adria roll-back7. Conversely, potassic-ultrapotassic magmas generated in a mantle source metasomatized by HS melts released along warmer subduction gradients would show constant low La/Ta and variable Th/La ratios. This is the case of the lamproitic magmas from the Tuscany Province  of the Interdepartmental Center “G. Scansetti” , equipped with a computer-controlled, automated X–Y mapping stage. Excitation line at 532 nm (solid-state Nd laser and 80 mW of emission power) was used, with Edge filter and a grating of 600 grooves/mm. Calibration was performed using the 521 cm49 and compositions, following the method previously proposed for these rocks35. The associated errors in resulting fluid major-element composition , minimizing oxide formation by reducing the ThO+/Th+ ratio below 0.5%, and maintaining the U+/Th+ ratio close to 1  Ky-host mineral analysis on the sample surface, and (ii) MSI analysis in the depth of the sample.29Si, previously determined by WDS electron microprobe51. Data reduction was performed using the Glitter software52. The US Geological Survey (USGS) reference standard BCR2G  was analyzed in each analytical run as quality control in order to assess the accuracy and the reproducibility of the analyses. Precision and accuracies are better than 10% for all the analyzed elements54. The analyses of quality controls utilized in the present study are reported in Supplementary table For Ky-host mineral analysis (i), the time-resolved spectra were characterized by ~50 s of gas background followed by ~60 s signal related to the mineral phase. External calibration was performed using NIST SRM610 and SRM612 glasses standards in conjunction with internal standardization using 55. The first step consisted in the determination of the cumulative Ky-host plus MSI trace-element content. To do this, the gas background is acquired for ~50 s  using 29Si as internal standard51. The concentration of 29Si was calculated utilizing the following relation:2 concentration of the MSI’s reported in Table 2 concentration analyzed by WDS, respectively. Finally, the relative mass fraction x of the MSI (mMSI) over the total ablated mass (mMSI+Ky host) was estimated as follows55V and ρ correspond to volume and density values, respectively55.Unexposed MSI (10–35 µm in diameter) trace-element determinations (ii) was performed with a two-step procedureVMSI, each MSI, having a negative crystal shape, was approximated as a parallelepiped where the x-, y- and z-axes are quantified by using an optical microscope. The volume of the ablated material during the acquisition of the segment C  of the MSI55In order to estimate CiKy host is the trace-element content of Ky-host, CiMSI+Ky host is the concentration of the mixed analysis and x is the mass ratio defined in the Eq. (CiKy host, CiMSI+Ky host, and x respectively. The resulting uncertainties are also reported in Supplementary Table In the above equation  the Eq. . ResultsSupplementary information


The present study examined the effects of physical exercise on attentional processes in individuals diagnosed with Attention Deficit Hyperactivity Disorder (ADHD), compared to healthy controls. Unlike previous studies typically comparing performance on baseline measures with post-exercise performance, this study examined the effects of physical exercise on attention while participants were engaged in a continuous performance task. Fourteen individuals diagnosed with ADHD  and 17 controls  completed the Conners Continuous Auditory Test of Attention (CATA). All participants completed the test twice, at baseline in a sitting position and while walking on the treadmill at a speed of 5 km/h. The order of administration was counterbalanced for each group. A 2 × 2 ANOVA with repeated measures detected a group by activity interaction on several measures of the CATA. Specifically, compared to baseline, the ADHD group demonstrated faster reaction times during physical exercise (25.4 ms faster) and decreased omission errors (1.5% better), whereas controls showed the opposite pattern . Importantly, the ADHD group’s overall relatively lower performance on these measures was only evident in the resting condition, attaining scores similar to controls during exercise. These results suggest a possibly hypoactive attentional system in ADHD that could potentially be enhanced by arousal through engagement in physical exercise. Attention-Deficit/Hyperactivity Disorder (ADHD) is characterized by difficulties paying and/or sustaining attention, often accompanied by deficits in controlling or inhibiting behavior . In effoAccumulating data suggest a positive effect of physical activity on cognitive functioning in ADHD. These positive effects are supported both by animal and human studies. Most prior studies examined the effects of physical activity on attention by assessing attentional performance before and immediately following physical training SD = 4.27, range 18–42), and their average years of education was 15.6 . Fourteen participants had a formal diagnosis of ADHD, given by their neurologist or psychiatrist, and 17 participants served as controls, with no history of psychiatric or neurological diagnoses. Mean age of ADHD diagnosis was 15.7 (SD = 4.39), with 42% hyperactive type. Most ADHD participants (71%) had prescriptions for a stimulant medication . Upon arriving at the lab, participants received a full explanation of the research procedures from a trained research assistant. All participants then gave a written informed consent according to procedures approved by the Bar-Ilan University Institutional Review Board.Participants were 31 physically healthy Bar-Ilan University students (74.2% women), who were recruited through ads placed around the university campus and on the internet. The sample’s average age was 24.13 (All participants completed the Conners Continuous Auditory Test of Attention (CATA), administered on a Dell Pentium computer, driven at 160 Hz. The CATA is a standardized continuous performance test, with negligible practice effects . It is aThe measures used in the present analyses are described in detail elsewhere . Below i(1)Detectability (DPR) is a measure of the respondent’s ability to discriminate targets  from non-targets , with higher raw and T score value indicating worse performance .(2)Hit Reaction Time (HRT) is the mean response speed, measured in milliseconds, for all non-perseverative target responses made during the entire administration.(3)Omissions (OMI) are missed targets, indexed by the percent of non-responses to targets.(4)Commissions (COM) are incorrect responses to non-targets, indexed by the percent of responses to non-targets.(5)C is a signal detection statistic that measures an individual’s natural response style and can be classified as having a conservative style that emphasizes accuracy over speed, a liberal style that emphasizes speed over accuracy, or a balanced style that is biased neither toward speed nor toward accuracy. Higher T scores represent more conservative response style.The test was administered twice, at baseline in a sitting position and while walking on a York treadmill  at a speed of 5 km/h, both closely supervised by a trained research assistant. Given the moderate intensity of this activity, no “warm-up” period was included, and the entire duration of the exercise was 14 min, which is the time needed to complete the CATA. The order of administration was counterbalanced for each group. Participants with ADHD were instructed to refrain from using medications on the day of the experiment, and all participants were instructed to refrain from drinking coffee or high-sodium drinks.post-hoc analyses with Bonferroni correction to decompose the two-way interactions. Exercise was the within-subjects variable and ADHD diagnosis was the between-subjects variable. All the aforementioned measures generated by the CATA were converted to T-scores and entered as dependent variables.Due to significant age difference between the ADHD and control groups, exploratory analyses for identification of outliers were conducted for age-matching. These analyses identified one 42-year-old participant in the ADHD sample, who was excluded from subsequent analyses. Potential age and gender differences between the groups were examined using independent samples and Chi-square test, respectively. A 2 × 2 analysis of variance (ANOVA) with repeated measures was used to investigate the effects of exercise on attention, followed by M = 24.8, SD = 3.49) and control  groups, t(28) = 2.10, ns. No significant differences were furthermore found in the distribution of males and females in each group . The procedure was well tolerated by all participants, with no dropouts.Independent samples s detected no significant age difference between the ADHD  and less omission errors (OMI) while walking, as compared to sitting, and their relatively lower performance on these measures was only evident in the resting condition, attaining scores similar to controls during exercise.These findings are in line with accumulating evidence suggesting the benefits of participating in physical exercise programs for adults with ADHD . ImportaSeveral potential mechanisms have been proposed to underlie the beneficial effects of exercise in ADHD. Given the increased release of catecholamines during physical activity, In contrast to some prior studies e.g., , the conThe present study was an initial pilot to examine performance on CPT conducted concurrently with physical exercise, and its conclusions are limited by the relatively small sample size. Another limitation of this study is that all participants exercised at the same intensity level, without controlling for several important physiological parameters, such as aerobic fitness, heart rate, and BMI, which could have moderated individual responses. Nonetheless, significant interaction effects, with moderate effect sizes, were found on several key measures, suggesting a potential benefit of physical activity to attentional processes in adult ADHD. It adds to the growing body of research supporting the beneficial effects of exercise on cognitive functions. Together, these studies suggest that, in addition to the myriad of physical and cognitive benefits that can be derived from regular exercises, physical activity while performing attentional tasks may bolster cognitive performance in individuals with ADHD. Upon replication in larger samples, these findings could be readily translated to practical applications in the classroom or working environment. Pedaling on a stationary bicycle or walking on a treadmill during lecture or work may prove beneficial for both physical and brain health.This study was carried out in accordance with the recommendations of APA ethical guidelines, as approved by Bar-Ilan University Institutional Review Board. All subjects gave written informed consent in accordance with the Declaration of Helsinki.All authors have contributed significantly to the manuscript. YR conceptualized the study, analyzed the data, and wrote the manuscript. TA assisted in study conceptualization, data analyses and manuscript preparation, and collected the data.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.


What are the long-term trends in prevalence of attention-deficit/hyperactivity disorder among US children and adolescents over the past 2 decades?In this study of data from 186 457 children and adolescents aged 4 to 17 years from the National Health Interview Survey, a nationwide, population-based, cross-sectional survey conducted annually from 1997 to 2016, the estimated prevalence of diagnosed attention-deficit/hyperactivity disorder in US children and adolescents increased from 6.1% in 1997-1998 to 10.2% in 2015-2016.Among US children and adolescents, the estimated prevalence of diagnosed attention-deficit/hyperactivity disorder increased significantly between 1997 and 2016. Attention-deficit/hyperactivity disorder (ADHD) is common in US children and adolescents. It is important to understand the most recent prevalence of ADHD and its long-term trends over the past decades.To estimate the prevalence of diagnosed ADHD and 20-year trends from 1997 to 2016 among US children and adolescents using nationally representative data.In this population-based, cross-sectional survey study , surveys were conducted annually from 1997 to 2016. A total of 186 457 children and adolescents aged 4 to 17 years from 1997 to 2016 were included in this analysis. Data were collected through in-person household interviews with a parent or guardian. The data analysis was performed in January 2018.Attention-deficit/hyperactivity disorder diagnosed by a physician or other health care professional.P for trend <.001). All subgroups by age, sex, race/ethnicity, family income, and geographic regions showed a significant increase in the prevalence from 1997-1998 to 2015-2016.Among the included 186 457 children and adolescents , 14 704 children and adolescents  were reported to have ever been diagnosed with ADHD. The weighted prevalence of diagnosed ADHD was 10.2%  in 2015-2016. There were significant sex and racial/ethnic disparities in the prevalence of diagnosed ADHD. The prevalence was 14.0%  in boys and 6.3%  in girls, 6.1%  in Hispanic individuals, 12.0%  in non-Hispanic white individuals, and 12.8%  in non-Hispanic black individuals. Over the 20-year period, the estimated prevalence of diagnosed ADHD in US children and adolescents increased from 6.1% in 1997-1998 to 10.2% in 2015-2016  in US children and adolescents over a 20-year period, from 1997 to 2016. Early comorbidities concurrent with ADHD may include tic disorder, anxiety disorder, autism spectrum disorder, communication and specific learning or motor disorders , and intellectual disability.1 Long-term follow-up studies from childhood to adulthood found that children with ADHD, compared with those without ADHD, were more impaired in psychosocial, educational, and neuropsychological functioning3 and had higher risks for antisocial disorders, major depression, and anxiety disorders as adults.4Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neuropsychiatric disorder characterized by persistent and impairing inattention, hyperactivity, and impulsivity.Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition that 5% of children have ADHD, based on previous worldwide estimates in earlier years.6 The prevalence of ADHD varies across different countries, with a significantly higher prevalence in the United States than in European countries.7 Moreover, the prevalence of ADHD has changed over time. Several previous studies in the United States have shown an increase in ADHD prevalence over the past years.19 For example, an analysis of the National Health Interview Survey (NHIS) reported a 33% increase in ADHD prevalence from 1997-1999 (5.7%) to 2006-2008 (7.6%) among children and adolescents aged 3 to 17 years.8 Similarly, the National Survey of Children’s Health showed a 42% increase between 2003 and 2011 in the prevalence of diagnosed ADHD among children and adolescents aged 4 to 17 years.9The American Psychiatric Association states in the Information about the current prevalence of ADHD and its long-term trends over the past decades is needed to inform future research, clinical care, and policy decision making on ADHD. Therefore, we analyzed nationally representative data to estimate the most recent prevalence of ADHD diagnosis among US children and adolescents and the 20-year trends from 1997 to 2016.20 It is conducted annually by the National Center for Health Statistics at the Centers for Disease Control and Prevention. The NHIS is composed of a series of nationally representative cross-sectional surveys. With a large sample size and a relatively high response rate, the NHIS has become the principal source of information on the health of the civilian, noninstitutionalized household population of the United States.21 The NHIS survey methodologic reporting is consistent with the reporting standards by the American Association for Public Opinion Research.22 Annual sample size of the NHIS is about 35 000 households containing approximately 87 500 persons. In NHIS 1997-2016, the total household response rate ranged from 67.9% to 91.8% and conditional response rate for the sample child component ranged from 85.6% to 93.3%. The NHIS survey was approved by the National Center for Health Statistics Research Ethics Review Board. All respondents provided informed informed verbal consent prior to participation. The University of Iowa Institutional Review Board determined the present study was exempt from approval given the use of deidentified data. This study followed the American Association for Public Opinion Research (AAPOR) reporting guideline.The NHIS is a leading national health survey in the United States.20 Information about the sample child was collected by interviewing an adult, usually a parent, who was knowledgeable about the child's health.The NHIS collected data on a variety of health topics through in-person household interviews. For each interviewed family in the household, 1 sample child, if any, was randomly selected by a computer program.From 1997 to 2016, respondents were asked, “Has a doctor or health professional ever told you that [the sample child] had attention-deficit/hyperactivity disorder (ADHD) or attention-deficit disorder (ADD)?” Approximately 99.8% of the participants responded to this question. The respondents in the 2016 survey were further asked, “Does [the sample child] currently have attention-deficit/hyperactivity disorder (ADHD) or attention-deficit disorder (ADD)?” Demographic data, such as age, sex, race/ethnicity, family income, and geographic region, were collected using a standardized questionnaire during the interview. Race and Hispanic ethnicity were self-reported and classified based on the 1997 Office of Management and Budget Standards. Family income levels were classified according to the ratio of family income to federal poverty level lower than 1.0, 1.0 to 1.9, 2.0 to 3.9, and 4.0 or higher. Data analysis was performed in January 2018.23All eligible children and adolescents aged 4 to 17 years who participated in the NHIS were included in the present study. Only 0.2% of participants had missing information on ADHD diagnosis and were therefore excluded. We restricted the age range to 4 to 17 years because the clinical guidelines of the American Academy of Pediatrics recommended to initiate an evaluation for ADHD in children aged 4 years or older.P values for overall differences across strata were calculated using χ2 tests. Trends in the prevalence over time were tested using a weighted logistic regression model, which included survey cycle as a continuous variable and adjusted for age, sex, and race/ethnicity. To determine whether the secular trends differ across strata, interaction analyses were performed by including multiplicative terms of each strata variable with survey cycle in the aforementioned logistic regression models. All analyses were conducted using survey procedures in SAS, version 9.4 (SAS Institute). Two-sided P < .05 was considered statistically significant.We estimated the prevalence estimates with survey weights to account for unequal probabilities of selection, oversampling, and nonresponse in the survey. We also used survey design variables about strata and primary sampling units for each survey cycle. In this study, we combined each 2-year period  as 1 survey cycle . Among the included 18 107 children and adolescents aged 4 to 17 years  in 2015-2016, 1880 children and adolescents  were reported to have ever been diagnosed with ADHD. The weighted prevalence of ADHD diagnosis was 10.2%  in 2015-2016 . There wTo estimate the 20-year trends in diagnosed ADHD from 1997 to 2016, we included 186 457 children and adolescents aged 4 to 17 years . Among them, 14 704 children and adolescents  were reported to have ever been diagnosed with ADHD.P for trend <.001)  . All subd <.001) .19 and racial/ethnic differences26 in the prevalence of ADHD.In a nationally representative population, we estimated that the prevalence of diagnosed ADHD among US children and adolescents was 10.2% in 2016. The prevalence differed significantly by age, sex, race/ethnicity, family income, and geographic region. Similar to our findings, several previous studies also reported sex15 Taken together, these findings indicate a continuous increase in the prevalence of diagnosed ADHD among US children and adolescents. Previous studies conducted in the United Kingdom have also observed a significant increase in ADHD prevalence, although the prevalence estimates were substantially lower than those in the United States.2Over the 20-year period from 1997 to 2016, we found a significant increase in the prevalence of diagnosed ADHD from 1997-1998 to 2015-2016. We found a consistent upward trend across subgroups by age, sex, race/ethnicity, family income, and geographic regions. The temporal trends in this study were consistent with previously reported trends in ADHD prevalence among US children and adolescents during earlier years.7 In particular, changes in the Diagnostic and Statistical Manual of Mental Disorders criteria that established the predominately inattentive presentation of ADHD led to significantly increased diagnosis in girls, who often fail to demonstrate classic hyperactive symptoms. In addition, increased public awareness, improved access to health services, and improved referral from primary care and communities to specialty mental health services may increase the likelihood of ADHD being identified on screening and diagnosis.9 Increased rates of diagnosed ADHD among black and Hispanic youths might reflect increased access to care and decreased stigma in those communities for receiving an ADHD diagnosis. The execution of the Affordable Care Act may also have increased access to care in lower socioeconomic status and minority groups. There is a common perception that ADHD is overdiagnosed in the United States, but this perception was not supported by scientific evidence based on review of prevalence studies and research on the diagnostic process.27Nonetiologic factors may partly explain the apparent increase in the prevalence of diagnosed ADHD in this study. Over the past 20 years, there have been expanded continuing medical education efforts about ADHD that enhanced physicians’ sensitivity to the diagnosis of ADHD. Changes in diagnostic criteria may also contribute to the increased number of children being diagnosed with ADHD.21 In addition to genetic risk factors, environmental risk factors are believed to contribute to the development of ADHD.28 Prenatal and perinatal risk factors, including preterm birth, low birth weight, maternal cigarette smoking, and maternal use of certain medications or illicit substances during pregnancy, have been associated with ADHD risk.31 Attachment-related factors in early infancy have also been associated with ADHD in childhood.34 Environmental contamination, such as lead, organophosphate pesticides, and polychlorinated biphenyls exposure, during prenatal and/or postnatal periods is a possible risk factor for ADHD.30 In addition, nutritional deficiencies  may also be implicated in the development of ADHD.1 The contributions of these nongenetic and genetic risk factors to the etiologic source of ADHD, both separately and jointly, warrant further investigation.It remains to be understood how much of the observed apparent increase in diagnosed ADHD was attributed to etiologic factors; ADHD has a genetic component with an estimated heritability of 70% to 80%.This study has several strengths. First, this study was based on a nationally representative sample of the US population, which facilitates the generalization of the findings to a broader population. Second, a large sample size with a multi-racial/ethnic diverse population was available, allowing us to assess disparities in ADHD prevalence according to population characteristics. Third, with a series of nationwide population-based cross-sectional surveys, we were able to evaluate the secular trends in ADHD prevalence over a period of observations as long as 20 years.1 In NHIS 2016, we found that 85% of children and adolescents with a history of ADHD diagnosis were reported as currently having ADHD, which was similar to the number reported in a previous study.9This study has some limitations. First, ADHD was ascertained by parent-reported physicians’ diagnosis, which may be subject to misreporting and recall bias. Second, we did not know whether the children and adolescents with a diagnosis of ADHD still had ADHD at the time of the survey across the survey years except in NHIS 2016. Previous studies have shown that the core symptoms of ADHD tend to decline with age, but inattentive features of ADHD are more likely to persist.Among US children and adolescents aged 4 to 17 years, the estimated prevalence of diagnosed ADHD was 10.2% in 2015-2016, representing a significant increase in prevalence from 1997-1998. This continued upward trend in diagnosed ADHD among children and adolescents points to the need to better understand potentially modifiable environmental risk factors, as well as provide adequate resources for the diagnosis and treatment of affected individuals in the future.


To investigate timely access to and the time needed to complete the diagnostic path of children and adolescents with suspected attention deficit hyperactivity disorder (ADHD) in the 18 Italian Lombardy Region ADHD reference centers.Data of children and adolescents enrolled in the Regional ADHD disease-oriented Registry for suspected ADHD who requested their first visit in 2013–2017 were analyzed.The sample comprised 2262 children and adolescents aged 5–17 years who accessed the ADHD centers for diagnostic classification and management. The median waiting time was of 177 days (range 66–375) from the request for the initial appointment to the completion of the diagnostic path, with a three - fold difference between centers. In addition to the center, the strongest significant predictors of long waiting times were age comorbidities, the severity of the disorder, and having already completed some diagnostic procedures provided by the common standard path.To guarantee an equal standard of care in ADHD centers for all children and adolescents there is a pressing need to reduce the times to complete the diagnostic path. It is the task of both policymakers and each center to optimize the quality of the service and of the care delivered. Accessibility, availability, and quality of care are important for efficient and effective healthcare systems , 2. PromLong waiting times for a first appointment at Child and Adolescent Neuropsychiatric Services (CANPS) are one of the main reasons for user dissatisfaction with them . A long ADHD is one of the complex neurodevelopmental disorders causing developmentally inappropriate and impairing patterns of inattention, hyperactivity, and impulsivity  that canIn the Lombardy Region, where about 15% of the Italian pediatric population live, there is a network of 18 Regional ADHD reference centers, accredited by Regional health authorities as specialized ADHD hubs (Tier 3) of the CANPS network. A Regional ADHD Registry serves as a disease-oriented registry collecting information on all patients who access ADHD centers for diagnosis of suspected ADHD . The RegThe main aim of this study was to examine waiting times for ADHD assessment in the 18 Regional ADHD centers, their variables, and inter-center differences for children and adolescents enrolled in the Registry between January 2013 and December 2017 for suspected ADHD.Data stored in ADHD Registry database were extracted and analyzed for the present study. Written informed consent was obtained for all patients before data collection. Data were anonymized prior to use for research. Formal ethical review board approval was not required for the present analysis. The study will be reported according to the published STROBE statement for prospective cohort studies .DSM-IV-TR) approved by all involved clinicians [We used the methodology previously described and reporting details concerning: the local health setting , the chainicians , 25, theinicians .At the end of 2018 we searched the ADHD Registry to identify children residents in the Lombardy Region who requested their first visit to one of the 18 ADHD regional centers between 1 January 2013 and 31 December 2017, and completed the diagnostic procedure. We used spatial analysis to describe the distribution and ADHD center access according to place of residence, using the five-digit ZIP code to determine the local health protection agency (ATS) and the closest ADHD center for each child and adolescent. We assessed how the ADHD center characteristics and the anamnestic and clinical characteristics of the sample population contributed to the time needed for diagnosis, starting from the first request to the ADHD center.Geographic information system (GIS) software was used to generate maps  that illustrate the geographic distribution of the homes of participants and the location of the ADHD center by centroid geospatial resource. The characteristics of the 18 ADHD centers were summarized using descriptive statistics.Student’s t, Wilcoxon, and Kruskal-Wallis tests, and analysis of variance (ANOVA) were used to determine differences in population characteristics and between groups of subjects. Spearman’s rank correlation test was used to analyze the linear trend of wait times over the study period. Cross tabulations with chi-square, when appropriate, were done to explore the univariate associations.p < 0.05 was considered statistically significant. All analyses were done using SAS/STAT database .A generalized linear model (GLM) analysis was also carried out to assess how the wait time affected completion as the diagnostic path (“estimated waiting time”). All tests were two-sided, and A total of 2464 children and adolescents’ residents in Lombardy Region required for the first time a visit for suspected ADHD during the period considered, 2262 (92%) had completed the diagnostic procedure at the time of data extraction, and were included in this study. These children and adolescents had a median age of 9 years at their first visit , 1292 (85%) were males and 222 (15%) were females.The estimated rate of children requiring diagnosis varied across the 8 ATS with a range of 0.68–3.17 children for 1000 residents 5–17 years old. One thousand nine hundred seventy-nine children and adolescents (88%) attended an ADHD center within their ATS, 1726 (76%) the nearest their residence house, and 1656 (73%) attended the nearest ADHD center in their ATS of residence  was observed between centers for the mean waiting time for completing the diagnostic trial  youths per center. The range of median waiting time for the first visit was 14–212 days , and of 66–375 days  for the time from the request to the diagnosis without statistically significant differences between investigated years. A three times difference  criteria for ADHD diagnosis, whereas 151 (7%) had a chronic medical disease. As shown in Table Of the 2262 children and adolescents in the study 1954 (86%) were diagnosed with a psychiatric disorder, and 1553 (69%) met Using linear regression analyses to determine response variables in population characteristics and centers, 6 of 10 statistically significant characteristics from univariate analysis were confirmed , besides language delay associated with a longer waiting time from asking for the first visit to complete the diagnostic path Table .Table 3Estimated waiting times values according to GLM analysis were more closed than observed  of the care pathway is important because complex neurodevelopmental disorders  can have a dramatic impact on home and family life and timely access to CANPS is expected by everyone.The major findings of the present study can be summarized as follows: despite the common work shared over time a three times difference of waiting time for the similar diagnostic pathway was observed between centers. The size of waiting times between centers can be halved weighting for a few characteristics of children and adolescents attending each center. However, between center differences remain wide.The results therefore indicate that a critical and shared comparison of the centers organization can be done to make waiting times more homogeneous between centers. Consequently, critical points should be tackled in the individual centers through effective initiatives for improving and maintaining over time the quality of care. On the other hands at ATS level interventions for improving the effectiveness of care delivery are needed. The local distribution of ADHD centers should be reviewed by the Regional Ministry of Health since 27% of population attended a different center than that provided by the organization of regional services network. This affects the distribution of workloads of the individual centers, causes family dissatisfaction with the Health Service, and increases the costs attributable to the greater distance from residence that the family has to cope with –6. It isThe complexity of health care systems can produce inefficiencies in healthcare delivery, in particular in health areas such as mental services where organization settings and people involved are often loosely connected. Various approaches, such as the sociotechnical system  or the qHowever, a mandatory intervention for each center is to manage better their available resources as suggested from not having found any association between the population size of attenders, the hours of work dedicated to ADHD diagnosis and therapeutic paths, and the waiting time.A first and essential intervention to reduce differences between centers in the access should be the definition and utilization of common criteria of attitude and practice since the first request for an appointment. Appropriate prioritization, using different criteria  were set up and used in a real-world setting providing effective care of ADHD . DiffereThe study setting is part of a larger, multimodal project, and represents a distinctive tool for ensuring appropriate and shared diagnostic and therapeutic pathways of care in ADHD children between the 18 participating centers. This homogeneity of the diagnostic and therapeutic practice between centers is a strength to evaluate other dependent variables, as waiting time, that can affect the care.However, there is also the limitation that our findings refer specifically to the population accessing ADHD centers since only these hubs input data into the Registry about patients attending the center. Thus, although the 18 ADHD centers are public and cover the whole Region, it was not possible to evaluate initial appointment failures with patient losses.It was not the aim of the study to evaluate if waiting time affected the outcome of the therapy then undertaken, although timely access to healthcare is associated with improved health outcomes , 38. BesTo guarantee an equal standard of care in ADHD centers for all children and adolescents the management of ADHD must stay within a pathway that strives for optimal care. The first step is the access to the ADHD center, thus long waiting times for diagnosis are a sign of poor care, or at least of a questionable care, since its inception. Besides, long waiting times have a negative impact on family satisfaction, staff moral, and referrer’s opinion of the service. Last but not secondary, differences in waiting times for the same needs (characteristics of children and adolescents attending the ADHD centers) are a sign of inequalities. A few critical points affecting waiting times have been highlighted in the present study. There is therefore reason and duty to intervene and improve the care.


N-alkyl-(3-sulfopropyl)-D-glucosamine hydrochloride, containing 12 and 14 carbon atoms in the alkyl chain, and they may serve as an example of cationic surfactants. The newly synthesized compounds exhibit good surface properties, low value of CMC  and good wetting properties. These surfactants’ ability to produce foam is considerably higher than in the commercial surfactants. Moreover, antibacterial and fungistatic activity was carried out by well diffusion assay against the selected bacteria , yeasts  and filamentous fungi . It was shown that the resulting quaternary salts significantly inhibit the growth of tested microorganisms. Antibacterial and fungistatic activity of the surfactant compounds varied depending on the species of bacteria or fungi. The results of antimicrobial activity of new lactose derivatives indicate that the compounds exhibit larger or similar antagonistic activity against tested bacteria and fungi than typical cationic surfactant cetylpyridinium chloride.This work presents a synthesis method for new surfactants based on lactose. The compounds obtained belong to the homologous series of O-β-D-Galactopyranosyl-(1→4)- In the last few years there has been increased interest in work focused on synthesis and properties of new surfactants based on natural products. Literature present some examples of that type of surfactants based on sugars, sterols or fatty acids ,2,3,4. TTaking into account the properties of surfactants derived from natural products they can successfully replace the typical surfactants based on petrochemical sources. Some of them are produced on a large scale by various producers, such as the glucose-based alkyl polyglucosides (APG) a non-ionic surfactant made from vegetable oils and starch. Germany-based Cognis, now owned by compatriot firm BASF, is the world’s largest APG surfactant producer. US-based Colonial Chemical has produced sugar surfactants made from corn syrup and coconut oil since 2002, under the brand Suga and PolySuga. France-based Wheat Oleo is the producer of alkyl polypentosides (APPs) surfactants made from combined natural fatty alcohols and pentose sugars coming from agricultural by-products wheat bran and straw . SorbitoThe basic principle of sugar-based surfactants synthesis is fact that cyclic forms of sugars with a free reducing group react with ammonia, alkyl- and arylamines, esters of amino acids and urea derivatives giving the corresponding glycosylamines derivatives . Thus thN-alkyl-(3-sulfopropyl)-D-glucosamine hydrochloride, containing 12 and 14 carbon atoms in the alkyl chain, were prepared by a multistep reaction. In the first step a series of N-alkyl-lactosamines were synthesized. Lactosamine derivatives were synthesized according to the method described in detail in patent literature [The new sugar-based surfactants, belonging to the homologous series of O-β-D-Galactopyranosyl-(1→4)-terature  with theterature . The appN-alkyl-(3-sulfopropyl)-D-glucosamine hydrochloride. In the next step, the 3--1-propanesulfonic acids were obtained by the reaction of equimolar amounts of the corresponding N-alkyl-lactosamines and 1,3-propanesultone with methanol as a solvent. The reaction schema is presented in first part of All reagents used in reactions were analytical grade. D-Lactose monohydrate P.P.H. POCh Gliwice; 1,3- Propanesultone, Fluka AG, Chemische Fabryk Büchs; propan-2-ol P.P.H. POCh Gliwice; Methyl alcohol Chempur, Piekary Śląskie; Dodecylamine Sigma-Aldrich Steinheim; Tetradecylamine Fluka AG, Chemische Fabrik Büchs.1H NMR and 13C NMR (Varian Gemini 2000) at a frequency 300 Hz using deuterium oxide (D2O) as a solvent, and infrared spectra  attachment).The surfactants obtained along with intermediate reaction products were analyzed using spectroscopic and elemental analysis (Elementar Vario EL III) in order to confirm the structures of compounds obtained. Moreover, the structures were analyzed by means of nuclear magnetic resonance spectroscopy The wettability and surface activities of surfactants’ aqueous solution were studied by means of equilibrium and dynamic surface tension measurements using drop shape method (Tracker IT Concept). Measurements were performed at a constant temperature of 297 K. The time of surface tension measurements depended on concentration of surfactants in the sample; the measurements were stopped once the equilibrium was reached. As suggested in , the equThe foaming properties of aqueous solutions of surfactants were set in a glass apparatus using the Ross–Miles method in accordance with the standard ASTM00A51E47 . After cStaphylococcus aureus ATCC 33862 and Bacillus subtilis PCM 2021, as well as Gram-negative bacteria: Escherichia coli ATCC 8639 and Pseudomonas aeruginosa ATCC 10145. Antifungal activity was determined against yeasts Candida albicans ATCC 10123 and filamentous fungi Fusarium graminearum KZF 1, F. avenaceum KZF 3, F. oxysporum KZF 4, F. culmorum KZF 5, F. equiseti KZF 6, Alternaria alternata KZF 13 and Botrytis cinerea KZF 37. Filamentous fungi were obtained from the collection of the Department of Pesticide Investigation, Institute of Plant Protection–National Research Institute in Poznań, Poland. Antimicrobial activity of aqueous solutions of surfactants was determined by well diffusion assay against the selected microorganisms including bacteria, yeasts and molds. The group of bacteria consisted of Gram-positive bacteria: 6 spores mL−1. The mixture was poured in Petri plates.The bacterial and yeasts suspensions were prepared in sterile saline from 24 h cultures and standardized to obtain density 0.5 McFarland’s standard. Then, suspensions were overlaid with appropriate medium . The fungal suspensions were prepared in sterile saline with 50 µL of Tween-80 according to Kaur et al. . The tot−3. Tests were performed in triplicate and the mean values are presented.After medium solidification, the wells (10 mm in diameter) were cut with a sterile cork borer to which 100 µL of surfactants solutions were introduced. The plates were incubated in the temperature of 37 °C for 24 h (bacteria and yeasts) and at temperature 20 °C for 5–7 days, depending on fungal species. After incubation, the diameters of inhibition zones were measured in millimeters. All the surfactant solutions were prepared using water from the PURELAB Classic, Elga with resistivity = 18.2 MΩ·cm, at the concentration of 1.0 and 0.5 g·cmBoth the structures of intermediates as well as obtained surfactants were confirmed by spectroscopic methods and elemental analysis. The results for surfactants are presented below.O-β-D-Galactopyranosyl-(1→4)-N-dodecyl-(3-sulfopropyl)-D-glucosamine hydrochloride (C12S3L)1H NMR : δ = 0.84 , 1.23-1.27 10), 1.65 , 1.96 , 2.20  2.89-2.96 , 3.33-3.92 , 4.43 13C NMR : δ = 16.0 (CH3), 24.9, 26.6, 28.8, 29.3, 31.6, 31.9, 32.1, 32.2, 32.3, 34.3 (10 x CH2), 41.8 (CH2SO3), 50.3 (CH2), 62.5, 63.3, 70.8, 72.4, 73.0, 73.7, 74.8, 76.1, 76.6, 77.6, 80.7, 94.1, 98.0, 105.2 (CH2-lactose)−1Infrared (IR) (KBr): 3450, 2910, 1710, 1480, 1220, 1050, 890, 790, 720, 610, 520 cmAnal. Calcd: C, 42.46; H, 7.91; N, 1.05; S, 3.68. Found: C, 42.21; H, 7.91; N, 1.02; S, 3.03.Mp. 118 °C, Yield of final reaction 94%. O-β-D-Galactopyranosyl-(1→4)-N-tetradecyl-(3-sulfopropyl)-D-glucosamine hydrochloride (C14S3L)1H NMR : δ = 0.86 , 1.21-1.27 10), 1.69 , 1.98 , 2.18  2.90-2.96 , 3.32–3.92 , 4.43 13C NMR : δ = 17.9 (CH3), 23.6, 24.2, 24.9, 26.1, 26.9, 29.0, 29.6, 31.9, 32.1, 32.2, 32.3, 34.3 (12 × CH2), 41.8 (CH2SO3), 50.3 (CH2), 62.5, 63.3, 70.8, 72.4, 73.0, 73.7, 74.8, 76.1, 76.6, 77.6, 80.7, 94.3, 98.6, 105.1 (CH2-lactose) −1IR (KBr): 3440, 2920, 1710, 1480, 1220, 1050, 890, 790, 720, 610, 510 cmAnal. Calcd: C, 43.91; H, 8.15; N, 0.96; S, 3.49. Found: C, 43.39; H, 7.84; N, 1.20; S, 3.31.mp. 121 °C, Yield of final reaction 95%. The adsorption process of surfactants is a dynamic one. For surfactants with low surface activity, the adsorption reaches its equilibrium state within seconds up to hours . As was 2 groups in the alkyl tail of the quaternary cations, so that with some limitations, log CMC is a relative measure of hydrophobicity. The effect described therein and works cited is due to increased hydrophobicity of the tail length, which significantly affects their CMC. The same impact of the alkyl chain length on the CMC value was observed also for other sugar-based surfactants such as urinate and uronoamide derivatives of dodecyl glucuronolactones [lactones , gluconalactones ,13 and slactones .The critical micellar concentration is not only a measure of solubility for surfactants but also a criterion which determines the effective application of concentration for disinfection. The effectiveness of quaternary ammonium compounds (an example of cationic surfactants) is the highest at CMC value . It is cSzA and SzB are the coefficients of Szyszkowski equation.Additional physicochemical analyses on the basis of the surface tension data were carried out using the Szyszkowski equation :(1)γSz=γ∞), the minimum molecular area in the adsorption layer at the saturated interface (minA), and the Gibbs free energy of adsorption (ΔadsG) for the systems in question were calculated according to the Equations [γ0, AN, R, T stand for the interfacial tension at concentration c = 0 (71.2mN/m), the Avogadro constant (6.022·1023 mol−1), gas constant (8.314 J/mol·K) and temperature (294 K), respectively. The values of surface excess at the saturated interface Γ∞sz were calculated from Equation (1) and were equal to 0.046 and 0.034 for C12S3L and C14S3L, respectively.The e co values of adsorption parameters are presented in ∞ decrease, with an increasing number of carbons in the hydrophobic tail. The same relationship was observed in a homologies series of other cationic surfactants—2--N,N,N-tris (2-hydroxyethyl)-2-oxoethanaminium chloride [The surface excess at the saturated interface indicates the effectiveness of surfactant adsorption. It is closely related to the packing of surfactant molecules in the adsorbed film. The packing of adsorbed film at the air–water interface is an important factor in surfactant application such as foaming, wetting, detergency and emulsification. The values of Γchloride .minA increase with increasing number of carbons in the hydrophobic tail, suggesting that surfactants with shorter hydrophobic tails have higher packing densities at the air–water surface. This phenomenon could be explained by longer hydrophobic chains being more prone to curl [adsG are negative, indicating that the surfactants have a great ability to adsorb at the air–water interface, higher in the case of surfactant with a longer alkyl chain.The values of  to curl . The valN-alkyl-(3-sulfopropyl)-D-glucosamine hydrochloride. In order to verify the usage properties of new cationic surfactants derived on the basis of lactose, the ability to produce foam was also tested. A study of foaming properties of aqueous solutions of the obtained compounds was performed using a modified Ross–Miles method . These m3 foam [3 [N-dodecyl-(3-sulfopropyl)-D-glucosamine hydrochloride about 400 cm3. It is also very important to note that aqueous solutions of the surfactants at hand not only produce a very high column of foam but also exhibit high foam stability indicators. Comparison of the foamability of aqueous solutions of surfactants obtained with aqueous solutions of commercial soaps shows that solutions of lactose-based surfactants produce significantly more foam than the soap solutions. For instance, 2% solution of liquid soap or cocamidopropylbetaine produce about 290 cm3 foam  and 350  foam [3  respectiMany processes depend on wetting including those used in essential industrial processes as well. These processes include flotation, detergency, cosmetic, washing, lubrication, coating, deposition or enhanced oil recovery. Understanding and characterizing the wettability of solid surfaces through surfactants is thus of paramount importance for both theoretical study and practical application. Due to their bacteriostatic properties, cationic surfactants are widely used in cosmetic products and have contact with the skin surface. As it is very difficult to study surfactant adsorption and wetting properties on the human skin, polymer surfaces are often used as skin substitutes. As the human skin surface is classified as a low energy hydrophobic surface , the PMMThe physical and chemical properties of quaternary ammonium compounds strongly affect not only their fate but also their toxicity, bioavailability and biodegradability. Quaternary ammonium compounds with relatively long alkyl chains (>=14 carbons) are more effectively eliminated during wastewater treatment by adsorption to biomass or by adsorption to organic and inorganic solids once they are released to the environment. As a result, quaternary ammonium compounds with short alkyl chains (<14 carbons) are more mobile and bioavailable than quaternary ammonium compounds with longer alkyl chains. Therefore, exposure of microorganisms to quaternary ammonium compounds with shorter alkyl chains is more probable ,41.Fusarium, Alternaria and Botrytis. Antimicrobial activity of tested compounds was differentiated and appeared to be dependent on both surfactant structure and indicator microorganism. However, surfactants inhibited the growth of all examined bacteria and fungi. Gram-positive bacteria and yeasts were more susceptible to O-β-D-Galactopyranosyl-(1→4)-N-dodecyl-(3-sulfopropyl)-D-glucosamine hydrochloride, while the sensitivity of Gram-negative bacteria to both surfactants was comparable.Antifungal activity against filamentous fungi was more differentiated. It is worth noting that in some cases a completely clear zone around the well with tested compound was observed, while sometimes the zone of inhibition was connected with a distinct change in the structure and degree of mycelium. N-dodecyl-(3-sulfopropyl)-D-glucosamine hydrochloride showed the greatest antagonistic effect to F. graminearum. Growth inhibition zone was equal to 30 mm. Moreover, this compound limited the growth of F. oxysporum, F. equiseti, F. culmorum and F. avenaceum. No activity against A. alternata and B. cinerea has been observed. O-β-D-Galactopyranosyl-(1→4)-N-tetredecyl-(3-sulfopropyl)-D-glucosamine hydrochloride showed the highest antagonist activity against F. graminearum and slightly less against B. cinerea and F. culmorum. This surfactant also showed antifungal activity towards F. avenaceum, F. oxysporum and A. alternata. Nevertheless, in the case of F. equiseti O-β-D- Galactopyranosyl-(1→4)-N-tetradecyl-(3-sulfopropyl)-D-glucosamine, only hydrochloride restricted their growth.O-β-D-Galactopyranosyl-(1→4)-It can be concluded that a stronger antagonistic effect against filamentous fungi was manifested in a surfactant with 14 carbon atoms in the alkyl chain (3 mm). A comparison of antimicrobial activity of obtained surfactants with activity of commercial cetyltrimethyloammonium bromide (CTAB) and cetylpyridinium chloride (CPC) indicates higher or comparable activity of tested compounds ,43. Alternaria alternata and Fusarium equiseti is lower in comparison to the commercial well-known surfactants, or very similar to activity against Fusarium avenaceum, Fusarium oxysporum and Fusarium culmorum.Comparative studies indicated that lactose based surfactants showed a stronger bactericidal effect towards all tested bacteria than commercial compounds. However, it should be noted that the potency of fungicidal action against Listeria monocytogenes, Enterococcus faecalis, S. aureus, Gram-negative microorganisms including E. coli, P. aeruginosa, Salmonella enteritidis and Yersinia enterocolitica as well as against yeasts C. albicans. Except for S. enteritidis, which was more susceptible to lactose nervonate, other tested bacteria and fungi demonstrated similar sensitivity to both surfactants. A series of amphiphilic methyl glucopyranoside ethers synthesized by [Listeria monocytogenes, Enterococcus faecalis, E. faecium and S. aureus, including multi-resistant strains such as vancomycin-, methicillin- and daptomycin-resistant strains. It was also found that antimicrobial activity was related to the physicochemical properties of examined compounds. Also, other authors emphasise the relationship between structure and antimicrobial properties of sugar-based surfactants examined for surface activity, adsorption or aggregation behavior, as well as the antimicrobial activity of three saccharide-amide cationic surfactants varying in hydrocarbon chain length  [C. albicans and Aspergillus niger). The authors stated that antimicrobial activity depended on the chemical structure of molecules and length of hydrophobic chain with the highest activity demonstrated by surfactant containing 12 carbon atoms. These results are in agreement with some other reports [Although the literature confirms antimicrobial properties of cationic surfactants with sugar moiety, the information about antifungal activity towards filamentous fungi is pretty scarce. In addition, the authors underline that activity against microorganisms is dependent on structure, including the nature of carbohydrate moiety or hydrocarbon chain length, as was observed in papers referred to in this article , synthessized by  demonstrn atoms) . The resn atoms) , who syn reports ,49,50. OExperiments presented in this study lead to the conclusion that the lactose is a sugar which can be used as a substrate in the reaction of surfactants’ preparation. The evaluation of obtained surfactants’ surface properties indicated that these compounds have low CMC values and can significantly reduce surface tension. Moreover, new compounds have good wetting properties. Evaluation of foamability showed that lactose-based surfactants can be used as good foaming agents. The resulting surfactants exhibit not only excellent foaming ability but also the durability of produced foam. Results of antimicrobial activity of new lactose derivatives show that compounds exhibit larger or similar antagonistic activity against tested bacteria and fungi than typical surfactant-cetylpyridinium chloride.The focus of attention in our studies falls on systematic comparison of petroleum-based surfactants and sugar-based surfactants with the aim of highlighting the benefits of sugar-based surfactant platforms.