Other country-level associations were also found. Multiple variable analyses showed a significant association between salt iodine and strata (p < 0.001) in India, Ghana and Senegal and that salt grain type was significantly associated with estimated iodine content in all countries (p < 0.001). Salt iodine relative to the reference  ranged from 1.3  times higher for fine salt in Senegal to 3.6  times higher for washed and 6.5  times higher for refined salt in India. Sub-national data are required to monitor equity of access to adequately iodised salt. Improving household access to refined iodised salt in sealed packaging, would improve iodine intake from household salt in all four countries in this analysis, particularly in areas where there is significant small-scale salt production.Regression analyses of data from stratified, cluster sample, household iodine surveys in Bangladesh, India, Ghana and Senegal were conducted to identify factors associated with household access to adequately iodised salt. For all countries, in single variable analyses, household salt iodine was significantly different ( Universal salt iodisation (USI) is globally accepted as the most cost-effective public health strategy to prevent iodine deficiency. In 1994, the Joint UNICEF/WHO Committee on Health Policy recommended that all food-grade salt used by households, by food processing industries, and for animal feed; should be fortified with iodine as a safe and sustainable strategy for the prevention and control of iodine deficiency disorders (IDD) . HousehoDespite the global success there is an increasingly apparent inequity in household access to adequately iodised salt within some countries ,5,6. FacTherefore, we assessed the key determinants of household salt iodine content using data from iodine surveys conducted in Bangladesh, India, Ghana and Senegal during the period December 2014 to April 2015. All four countries have mandated the iodisation of household salt, introduced during the period 1989 (Bangladesh) to 2001 (Ghana) ,8,9,10. The main objective of this paper is to present the results of regression models designed to highlight which of the survey-related variables were most associated with household access to adequately iodised salt and whether these varied within each country. In brief, the surveys were, cross-sectional, stratified, multistage cluster sample design with probability proportional to size (PPS) selection of the primary sampling units (PSUs) within each stratum. Strata were determined to provide representative information for administratively or programmatically relevant domains. Households were systematically, randomly, selected within a PSU. Questions were included on a variety of indicators believed to be associated with household salt iodine content and access to adequately iodised salt. The target unit was the household. The first choice of respondent was a woman responsible for organizing food preparation in the household, usually the wife of the head of household, or the head of the household. The second choice respondent was a woman of reproductive age (WRA). Although a WRA was defined as being 15–49 years of age, women aged 18 or above were preferentially selected in Ghana, India and Senegal. Another adult member of the household was selected where nobody meeting these criteria was present.Stratification in Bangladesh, Ghana and Senegal was based on existing knowledge of the salt supply and designed to obtain representative data for areas expected to have low household coverage of adequately iodised salt. These were: in Bangladesh, low-performing areas, as defined by the national Control of IDD project, which tended to be harder-to-reach areas, border areas, and areas of small-scale seasonal salt production; in Ghana and Senegal, small-scale salt production areas, which were associated with operational challenges and leakage of unprocessed, non-iodised, salt into the local markets. In India, stratification was by urban and rural area within six defined geographical zones: South, West, Central, North, East and North-East . For all surveys, interviews were conducted in all selected and consenting households. Data collection was supervised and quality-assured by field supervisors, with coordination and technical assistance from survey management personnel at a central administrative level. All survey-related personnel were trained prior to the surveys, and survey tools and procedures were pilot-tested in a typical field setting. Apart from Bangladesh, replacement of households where a respondent was not at home or the potential respondent refused was not implemented.According to the different national protocols, a sample of 20–50 gm of salt was collected from all consenting households in each survey. Salt samples for each household were kept in re-sealable bags coded with the unique household identification number. Bags for all household samples from each cluster were stored in opaque bags/envelopes at room temperature until analysis of the salt iodine content at a central laboratory.In three countries , data were collected using mobile devices with pre-coded skips and cross-checks to ensure data quality. In Bangladesh, data were collected using paper forms. Data quality was ensured in all cases by random repeat interviews; by end-of-day checks and follow-up by field supervisors. Electronic data were regularly reviewed and monitored for completeness. In Bangladesh, validated double data entry with checks for valid ranges, legal values, and consistency was conducted then the two data sets were reconciled.The survey questionnaires in all countries included modules to classify residence type , consent, and recording of collection of a household salt sample. Questions were also included to determine the household Multidimensional Poverty Index (MPI) score ,16, respThe MPI is comprised of three scored domains, with sub-components, for each of health, education and living standards. Each domain was given an equal one-third weight in determining the overall MPI score. A household was classified as being deprived in any one domain if the score for that domain was greater than or equal to 0.3 . Where the overall MPI score was greater than or equal to 0.3 , the household was considered as being vulnerable to acute poverty.The primary outcome indicator for the survey was household coverage of adequately iodised salt, assessed as the percent households using salt with ≥15 mg/kg of iodine. Additional salt iodine related indicators are presented in respective national survey reports  ,19.All salt iodine results are based on quantitative analysis of salt iodine content by the iodometric titration method . An extephoda  for India.Salt grain type was assigned by the laboratory staff to reduce subjectivity that can occur with assessment by many different field staff. Grain type categories were assigned based on physical characteristics and national terminology as fine or coarse for Bangladesh, Ghana and Senegal; and as refined, washed, crystal or The Statistical Services Centre (SSC), University of Reading, United Kingdom conducted the initial survey data management and analyses for surveys in Ghana and Senegal; and provided technical support to the International Centre for Diarrhoeal Disease Research (icddr.b) and the All India Institute of Medical Sciences (AIIMS), New Delhi for these processes for surveys in Bangladesh and India respectively. All remaining analyses for this manuscript were conducted by one of the paper authors (SD). Regression models were built with inclusion of the three domain-specific MPI scores for education, health and living standards, instead of the overall MPI score, to allow for more refined analysis of factors associated with salt iodine content. All analyses were conducted separately for each country.Results are presented for the percent households using adequately iodised salt (≥15 mg/kg iodine) at the time of the interview, the median and mean salt iodine content from all households with salt samples along with the inter-quartile range (IQR) and the 95% confidence interval (CI) around the median and mean, respectively. All data presented in this paper are for households with a valid salt iodine result, weighted for the relative proportion of the population in each stratum.p-Values presented are based on the Wald test determining the overall significance of each variable. Significance was set as a p-value <0.05.Salt iodine content was analysed against multiple different factors using general linear models, with household weights and robust variance estimation accounting for survey design effects using the survey library “Survey: analysis of complex survey samples” within the R statistical analysis package version 3.31 . p-Valuep-values are not adjusted for multiple comparisons; many of the factors considered are explicitly non-independent  so a naïve adjustment measure would not be appropriate. However, the number of tests being conducted should be taken into consideration when considering the significance of variables with borderline p-values, between 0.01 and 0.05.For single variable regression analysis, p-value of 0.1 as the inclusion criteria. Differences were represented by the p-value for variable effect. The final model included interaction by strata to investigate if and how associations between variables and salt iodine content varied by strata. In India, this was modelled using interaction by urban/rural residence and interaction by zone to simplify interpretation and graphical representation. The significance of differences were represented by the p-value for interaction with strata/zone effect and also graphically as the estimated household salt iodine content  for some of the significant (p < 0.05) associations for each country.For multiple variable regression analysis, all variables included in the single variable analysis were considered for inclusion in the models except for residence type where this was included in the definition of the strata . A stepwise selection procedure was conducted using a The national surveys were approved by national or academic Institutional Review Boards in each of the four countries. All protocols required consent for the interview and for collection of a salt sample. Further details of individual survey design, tools, and data management, adjustments, and analysis can be found in the full survey reports ,19,21  for each of the four countries are included in Results for household coverage with adequately iodised salt and results of the single and multiple variable regression analyses are shown in Strata-specific mean household salt iodine and household coverage with adequately iodised salt was found to be lowest in areas that included significant levels of small scale salt production in Bangladesh, Ghana and Senegal; and highest in more urbanised areas of all four countries.p < 0.001), and was significantly higher among households: with non-deprived MPI living standards (p ≤ 0.002), with a respondent who had heard of iodised salt (p ≤ 0.013), with a respondent who looked for iodised salt at the time of purchase (p < 0.001), where salt was obtained in a sealed pack (p < 0.001), and where the salt was of a more refined grain type (p < 0.001). For three of the four countries, household salt iodine content was significantly higher among: households of urban residence type ; households non-deprived in the MPI Health domain ; where salt was from a major brand, and where the salt packaging had an iodine label or logo . In Ghana and Senegal, household salt iodine was also found to be significantly higher among households non-deprived in the MPI education domain (p ≤ 0.028).For each of the four countries, single variable regression analysis showed that household salt iodine content was significantly different between strata .Despite the significant differences in salt iodine content between the 12 strata from the India survey, the mean household salt iodine content was relatively consistent and adequate within all strata: the mean (and 95% CI) ranged from 19.7 mg/kg  in the South-rural stratum to 30.4 mg/kg  in the North-urban stratum. Respective strata level household coverage with adequately iodised salt were 55.4%  and 95.9% . The mean household salt iodine was above 15 mg/kg for almost all variable sub-groups in India, except where salt was not obtained in a sealed pack , and where the salt grain type was crystal or For Bangladesh and Ghana, the household salt iodine content varied greatly by strata and by variable sub-group. In Bangladesh, the mean (and 95% CI) iodine content by strata ranged from 12.4 mg/kg  in the rural-low-performing stratum to 24.3 mg/kg  in the urban stratum. Respective strata level household coverage with adequately iodised salt were 25.1%  and 68.7% . In Ghana, the mean (and 95% CI) iodine content by strata ranged from 13.8 mg/kg  in the South-salt-producing stratum to 32.3 mg/kg  in the South non-salt-producing stratum for Ghana. Respective strata level household coverage with adequately iodised salt were 19.3%  and 48.6% . Salt iodine was particularly low (mean <10.0 mg/kg) among households where salt was of a coarse grain type  in Bangladesh and Ghana respectively, and, in Bangladesh, where salt was not obtained in a sealed pack . In both countries, the highest mean household salt iodine content was found for households where the respondent had looked for iodised salt at purchase: mean 32.0 mg/kg  in Bangladesh and mean 45.6 mg/kg  in Ghana.In Senegal, household salt iodine content was consistently low by strata and variable sub-group. The mean (and 95% CI) by strata ranged from 8.8 mg/kg  in the rural-salt-producing stratum to 17.8 mg/kg  in the urban stratum. Respective strata level household coverage with adequately iodised salt were 10.9%  and 53.3% . There were no sub-groups in Senegal where the mean household salt iodine was ≥20 mg/kg. The highest mean salt iodine was found among households using fine grain salt .p value variable effect <0.001). Relative to the reference , salt iodine content ranged from 1.3  times higher for fine salt in Senegal to 6.5  times higher for refined salt in India. See Multiple variable regression analyses showed that the iodine content was significantly higher in a more refined salt grain type in all four countries . In India, Central-rural was the only stratum where household salt iodine was significantly higher  than in the reference stratum of South-urban. Other variables that showed a significant association with higher household salt iodine were: the respondent looking for iodised salt at the time of purchase, 1.6 times  in Bangladesh and 1.7 times  in Ghana; obtaining salt in a sealed pack, 3.8 times  higher than loose salt in Bangladesh; using salt from a leading market brand, 1.5 times  higher than for no brand in India; and households being non-deprived in the MPI health domain, 1.1 times  higher than salt in households deprived in the MPI health domain in India.In India, Ghana and Senegal, the association between household salt iodine content and strata was still significant in the multiple variable regression  into the model revealed new results. The significance of these interactions are shown in the last column of Statistically significant interactions that could be meaningfully interpreted are presented in p = 0.030), India (p < 0.001), Ghana (p < 0.001), and Senegal (p = 0.011). For Bangladesh, the only pairwise significant difference in estimated household salt iodine content  and for the MPI living standards domain in Senegal (p = 0.036). For Bangladesh the sample size for households deprived in this domain was small, n = 132 nationally, making the one pairwise difference between estimated salt iodine from rural-low-performing (higher iodine) and rural-other households difficult to interpret. Other than for some of the packaging-related variables, the only other significant differences found for strata level interactions with estimated household salt iodine were for the MPI health domain in Bangladesh , socio-economic status (particularly the MPI living standards domain), knowledge and awareness of iodised salt (having heard of it and looking for it at the point of purchase), and salt supply . The results of the multiple variable regression analysis provide a clear indication that various characteristics of the salt supply are the most important factors associated with household salt iodine level. In particular, the level of iodine in refined salt was considerably higher than in larger coarse and crystal salt. These results also highlight the high level of sub-national variation in the quality of salt accessible to households.The tendency for lower income, rural, households to have greater access to non-iodised or inadequately iodised, presumably lower-priced, salt has been reported previously ,6,22,23.Another main finding was that the highly significant single variable associations between salt iodine and salt supply-related factors, such as packaging and brand name, were generally reduced when grain type was held constant, suggesting an overlap between these factors, as would be expected. Experience has shown that salt with a finer grain type is more likely to be: iodised homogenously, subject to production quality control and regulatory monitoring, packaged and labelled as iodised, and to be produced by a larger scale producer with a known brand name .The low household access to adequately iodised salt in small-scale salt producing areas of Bangladesh, Ghana and Senegal indicates a lack of progress following efforts, over many years, to improve salt iodisation technology and quality assurance capacity among small-scale producers ,26,27,28As previously reported , India hIn Bangladesh, the survey report  and the In Ghana, the higher iodine content of coarse salt in the North compared with the Mid strata is difficult to explain, however, may be related to the expectation of increased regulatory monitoring check points during the longer journey to retail points in the North. Despite this difference, the fact that the mean iodine level of coarse salt was below 10 mg/kg in all four strata indicates that a similar strategic response is required to ensure that this type of salt is adequately iodised. The national MUIC among WRA of 202 µg/L indicates adequate iodine intake among this population group, suggesting that sources of dietary iodine, other than iodised household salt, are available . Sources could be naturally occurring iodine and/or iodised salt used in frequently consumed processed foods, such as bouillon and tomato paste. One study conducted in the North of Ghana supports this hypothesis .In Senegal, it appears that within each of the urban and rural-salt-producing strata, access to iodised household salt was consistent. Within the urban stratum, the majority of households were using salt with just about adequate iodine content, whereas in the rural-salt-producing stratum, household salt tended to have very low estimated iodine content. In contrast, households in the rural non-salt-producing stratum were accessing salt with either relatively high or else low level of iodine. The MPI living standards score appeared to be a key driver of access to better iodised salt in this stratum, suggesting that salt of varying quality was available, but that access to higher quality iodised salt was associated with salt pricing/affordability. Until the challenge of small-scale supply of lower-iodisation quality salt is addressed, it is unlikely that much can be done to influence the effect of the socio-economic factor on household salt use. In contrast to the findings in Ghana, the low percent access to adequately iodised salt was reflected in a relatively low MUIC (98 µg/L) among WRA nationally . The iodine content of household salt is an important indication of iodine intake from salt iodisation, however, there is now a large body of evidence indicating that industrially-processed food salt is an increasingly important source of, potentially iodised, salt ,34. FoodIt was possible to apply the same regression model in each country and conduct some comparison between them because they were designed with similar questionnaire modules. In addition, the stratification design and multiple regression analyses provided results that can be used as an evidence base for future programme strategies to increase equity of access to adequately iodised salt. A national process for dissemination and strategic use of these findings has been encouraged in all four countries.The external quality assurance of laboratory performance rated all four laboratories conducting salt iodine analyses as “Good”, providing confidence in the salt iodine results.A limitation to the sample size in Senegal occurred due to the misplacement of salt samples from 13 PSUs across different strata. Salt iodine data were adjusted for this since the occurrence could not be considered as random non-response. The non-response for valid household salt iodine results in Ghana was random and more related to households that typically purchased small quantities of salt and not having any in the household at the time of the survey, and to collection of insufficient salt for analysis.Disparities in household access to adequately iodised salt has been a common observation in a number of countries, even after a period of years implementing salt iodisation. This awareness reinforces the importance of collecting representative sub-national data and using these data to improve programme performance and ensure that all segments of populations are reached with sufficient iodine through adequately iodised salt to meet minimum physiological needs. Designing surveys with standardised modules, programme-related stratification, quantitative assessment of salt iodine, and using multiple variable regression as part of the data analysis, can greatly improve this sub-national evidence base. It also provides a baseline from which to monitor the impact of implementation.Improving household access to quality-assured refined iodised salt in sealed packaging, would improve dietary iodine intake from household salt in all sub-national areas included in this analysis, in particular in areas of small-scale salt production. Based on a review of many initiatives to improve the quality of small-scale iodised salt production , it is l


The plants growing in tailings were distinctly enriched in Cu, Cd, Co, Ni, and Pb, and the concentration of copper achived the critical toxicity level in shoots of Cerastium arvense and Polygonum aviculare. The redundancy analysis demonstrated significant relationship between the concentration of available forms of studied elements in substrate and the chemical composition of plant shoots. Results of the principal component analysis enabled to distinguish groups of plants which significantly differed in the pattern of element accumulation. The grass species Agrostis stolonifera and Calamagrostis epigejos growing in the tailings accumulated significantly lower amounts of Cu, but they also had the lowest levels of P, Fe, and Zn in comparison to dicotyledonous. A. stolonifera occurred to be the most suitable species for phytostabilization of the tailings with regard to its low shoot Cu content and more efficient acquisition of limiting nutrients in relation to C. epigejos. The amendments improving texture, phosphorus fertilization, and the introduction of native leguminous species were recommended for application in the phytoremediation process of the tailings.Copper ore mining and processing release hazardous post-flotation wastes that are difficult for remediation. The studied tailings were extremely rich in Cu (1800 mg kg Mining and processing of copper ores extensively alter the environment, and the main difficulty is a huge amount of flotation tailings which comprise even 96% of the mass of run-of-mine ores with worldwide production estimated to be two billion tons in 2011 Gordon . These tAmong the technologies that may be employed in remediation of metal-contaminated lands and especially in the case of large sites, phytoremediation constitutes the most useful and cost-effective way that can be applied with minimum environmental impact  which is located in Warta Bolesławiecka district, Lower Silesia province, SW Poland  Roth (both from the Poaceae family), Cerastium arvense L. (Caryophyllaceae), Polygonum aviculare L. (Polygonaceae), and Tussilago farfara L. (Asteraceae). Samples of these species and substrates were collected from the tailings pond and the reference site, and they consisted of aboveground plant parts and copper tailings or reference soil taken from the plant rooting zone (10–20 cm depth). In the tailings pond, each species with substrate was collected randomly from three to five sampling sites. There were ten sampling sites in total with different compositions of collected species. At the reference site, the samples were taken randomly from four quadrates of a surface area 25 m2 with similar plant composition.Because of the extremely poor vegetation that covers the pond, only five herbaceous plant species could be examined in this study, such as An analysis of granulometric composition of the copper tailings was carried out with use of the aerometric method. Organic carbon was determined by a CHNS analyzer from CE Instruments . Appropriate Sigma-Aldrich ICP standards were used for working standards after matching a matrix.Total contents of 13 elements  in the copper tailings were determined by ICP-OES after microwave digestion in concentrated nitric acid with hydrogen peroxide oxidation  and 0.05 mol L−1 HCl pH = 1.3 by Yanai et al.’s  in air-dried and sieved (Ø 2-mm sieve) samples of the tailings and the soil were determined after extraction in 0.2 mol Let al.’s  method. et al.’s  method w−3 HCl  was performed to evaluate the statistical significance of constrained axes as well as of each descriptive variable in the model of regression of forward selection. Computations and ordination plots in PCA and RDA were made using CANOCO 4.55 for Windows software  was performed to analyze the variance in element contents in plants and redundancy analysis (RDA) was used to relate variation in the chemical composition of plants to the element contents in examined substrates. These linear methods of ordination were chosen after preliminary application of detrended correspondence analysis (DCA) of the plant data, which yielded axes of short gradients, i.e., below 0.4 SD  which mainly derived from black shale and lignite that are present in copper ore deposits, and from flotation agents. Due to the high content of carbonate minerals, they are characterized by an alkaline reaction with the pH−1) which is almost 13 times higher than the maximum allowable content of this element in European agricultural soils, as reported by Kabata-Pendias and Pendias (−1) following EU legislation , and it exceeded the mean values of these elements for Polish as well as European soils, according to Lis et al.  and Salminen et al. . The levels of Co and Mn were also in accordance with the lower values of the allowable content of these elements in European agricultural soils, as given by Kabata-Pendias and Pendias ; thus, the copper tailings can be considered as Co- and Mn-contaminated. The total Fe and Ni contents were a few times as high as Polish soil average values  . The total Na content was much lower compared to the European mean.The total element contents found in the copper tailings are presented in Table  Pendias   in terms of content of the available forms of all analyzed elements , and this was about seven times as high as that from the soil. As opposed to the other species, T. farfara accumulated calcium at a very high level (21 g kg−1), which was the same in both study sites. The shoot Mg content was considerably higher in the plants from tailings, and P. aviculare, C. arvense, and T. farfara accumulated magnesium above the requirement for optimal plant growth, according to Marschner (−1). Among the species growing in tailings, grasses, i.e., A. stolonifera and C. epigejos, were characterized by the lowest Ca and Mg levels. The plants from copper tailings, relative to those from the soil, accumulated phosphorus at the same level as in the case of dicotyledonous, or had a significantly lower P content  than in both grass species with the lowest result noted in C. epigejos. The K accumulation pattern differed widely among the studied sites and the species. The plants from tailings had much higher Na content with the highest result (78.7 mg kg−1) found in P. aviculare which accumulated 17 times as much sodium as that from the soil.A comparison of chemical composition of plant shoots collected from the copper tailings and the reference soil revealed the occurrence of many considerable differences Table . The plaarschner   in all plants from tailings compared to those growing in the reference soil. The highest amounts were found in C. arvense and P. aviculare . These values were nearly eight and ten times as high as those of the soil environment, and they were within the range of critical toxicity Cu level for plants, according to Kabata-Pendias and Pendias (−1) as well as the European Union legislation  but below the toxic levels, as given by Kabata-Pendias and Pendias . The species from tailings were distinctly enriched in Ni and Pb whose contents approached the maximum of the normal ranges  were found in most cases. The iron levels for the examined grasses were below the range of critical deficiency concentration  was within a range of the critical deficiency concentration given by Marschner (−1).The shoot Fe content was much lower in all species growing in tailings compared to those from the soil, and statistically significant differences (arschner ), and tharschner  (5–20 mgr ranging from 0.96 (Cu) to 0.85 (Co), respectively; the influence of Ni was much weaker (r = 0.56). The second component mainly represented the gradient of Fe, P, and Zn . Values of the variables which determine the first and second principal components are linearly uncorrelated.In PCA, the highest eigenvalues were achieved for the first two principal components  which explained 73.6% in total of the variability in shoot element contents. The first principal component was strongly determined by Cu, Mg, Pb, Na, Ca, and Co with the linear correlation coefficient T. farfara, formed one group where the first axis returned negative scores  and the second axis returned high positive or close to zero scores . The plant samples from tailings were divided into two clearly separated groups of various species. The first one consisted of C. arvense and P. aviculare which had the highest positive scores of the first axis  and positive or close to zero scores of the second axis . The second one included A. stolonifera and C. epigejos which differed from the other samples from tailings by the lower scores of the first axis and had the lowest scores of the second axis. These two grasses accumulated significantly lower amounts of most elements considerable in this PCA model i.e., Cu, Mg, Na, Ca, Co, Fe, P, and Zn, in relation to C. arvense and P. aviculare growing in tailings  as well as T. farfara but in this case without Zn . These species also differed significantly in levels of Fe, P, Cu, Ca, Ni Na, and Zn  compared to the group of samples from the reference soil. The samples of T. farfara, both from the soil and the copper tailings, were placed in a central part of the diagram and were not sharply separated from each other or from the other samples. T. farfara from soil differed significantly from the other species growing in the same environment by higher contents of Ca, Co, Pb, and Mg , whereas T. farfara from tailings contained considerably lower amounts of Mn, Zn, Cu, Mg, and Pb than C. arvense and P. aviculare from the same study site .The PCA ordination Fig.  indicateP = 0.002), whereas the second axis was not significant in this model. The forward stepwise selection of variables revealed that each of the subset of the explanatory variables, i.e., the concentration of Mn, Ca, Zn, Mg, Cu, and P, was statistically significant  when tested independently and explained the variation at the comparable level, Lambda 1 = 0.31 (Mn) to 0.27 (P). In addition, all these six descriptors were highly cross-correlated , but the values of Mn, Ca, Mg, and Cu were mutually negatively related to Zn and P. The explanatory effect of Co concentration in substrates was also significant but lower than others . The effect of K and Fe levels in substrates appeared to be insignificant.Redundancy analysis (RDA) demonstrated a significant relationship between element contents in plants and concentrations of the available forms of elements in substrates. In the resulting RDA model, nine tested explanatory variables, i.e., the concentration of available P, K, Ca, Mg, Fe, Cu, Co, Mn, and Zn in substrates, explained 43.5% of the total variability in the element contents in plant samples. The first canonical axis accounted for 33.5% of the variation and was highly statistically significant 2 Ksp = 1.4 × 1029, Mg3(PO4)2 Ksp = 6.3 × 1026] , because this symbiosis commonly occurs in both these species and was found in their roots in the reference soil (unpublished data). In the copper tailings, typically mycorrhizal species A. stolonifera, C. epigejos, and T. farfara realized P uptake only by their root mechanisms, which resulted in P deficiency in the case of the grasses.Low amounts of phosphorus were detected in shoots of the species from copper tailings despite of its high total content in this substrate. The low bioavailability of this element can be attributed to high pH, and the abundance of calcium-magnesium carbonates occurred in the tailings. The excess of carbonates intensifies P sorption on their surface, and the high content of Ca and Mg increases phosphorus precipitation in the soil solution as Ca-Mg phosphates Lindsay  which arA. stolonifera and C. epigejos as well as in differences in levels of accumulation of other metals that were present in these both grass species in tailings conditions.The alkaline soil environment strongly modifies the Fe uptake (Schenkeveld et al. C. arvense, P. aviculare, and C. epigejos. According to Lambers et al. (P value in C. epigejos from the copper tailings implies that this species has particular difficulties in P uptake in the tailings environment.Reaction of the soil solution also affects manganese availability but to a lesser extent than in the case of iron. According to Sanders , decreass et al. , plants s et al. . SimilarC. epigejos from tailings was comparable to the result obtained on alkaline ash deposits (Mitrović et al. A. stolonifera and C. epigejos growing in tailings from other plants by the lowest content of these elements. This implies a similar mode of acquisition mechanisms of these nutrients in these species which proved very little effective in the copper tailings conditions.The copper tailings had low zinc content. Additionally, the uptake of this nutrient is also limited at high pH and carbonate content and clay minerals can strongly absorb this element Alloway . The lowA. stolonifera due to its demonstrated low shoot heavy metal content, which is important in the context of entering these elements into the food chain. In contrast to C. epigejos, creeping bent grass also acquired limiting nutrients P, Fe, and Zn more efficiently, which can result in a competitive advantage of this species in a plant community on the tailings. Considering also our earlier results (Spiak et al. Trifolium and Medicago genera using seeds inoculated with Rhizobium bacteria. As hosts for rhizobia and arbuscular mycorrhizal fungi, these plants can fix nitrogen and uptake phosphorus more effectively, which enhances both their growth and that of neighboring plants. It seems that legumes could effectively colonize the tailings because high Ca and Co contents enhance their nodule formation (Smit et al. The investigation contributes towards a better understanding of the mechanisms used by plants to respond to specific properties of tailings from the copper mining industry in an effort to develop an efficient strategy for their remediation. The most suitable plant species for this process proved to be Polygonum aviculare and Cerastium arvense had high shoot accumulation capacity of all studied elements with the highest Cu contents lying within the range of critical toxicity for plants, whereas the grass species had lower levels of majority of elements, especially Cu, P, Fe, and Zn. Agrostis stolonifera proved to be the most suitable species for phytostabilization of the tailings with regard to its low shoot heavy metal content and, as opposed to Calamagrostis epigejos, more efficient acquisition of the limiting nutrients. The remediation process of the tailings, in view of potentially high costs, should at least involve the application of amendments improving their texture, phosphorus fertilization, and the introduction of native leguminous species.The tailings from the copper mining industry had a lot of unfavorable features for vegetation development, especially the adverse air-water conditions, the low availability of nutrients such as P, Fe, and Zn, and a very high content of Cu, Co, and Mn. The chemical composition of plants colonizing the tailings reflected the concentration of the available forms of Ca, Mg, P, Cu, Co, and Mn, but the species differed distinctly in their response to the tailings properties.


The objective of this study was to evaluate the risk of sialolithiasis in nephrolithiasis patients.Using data from the national cohort study from the Korean Health Insurance Review and Assessment Service, we selected 24,038 patients with nephrolithiasis. The control group consisted of 96,152 participants without nephrolithiasis who were matched 1:4 by age, sex, income, region of residence, diabetes, hypertension, and dyslipidemia. The incidence of sialolithiasis in the two groups was compared, with a follow-up period of up to 12 years. The crude and adjusted hazard ratio (HR) of nephrolithiasis to sialolithiasis was analyzed with a Cox-proportional hazard regression model.The rates of sialolithiasis in the nephrolithiasis group and the control group were not significantly different . The crude and adjusted hazard ratios of nephrolithiasis to sialolithiasis were not statistically significant . Subgroup analyses according to age and sex also failed to reveal statistical significance.There is no evidence of an increased risk of sialolithiasis associated with nephrolithiasis. We suggest that routine evaluation for sialolithiasis in all patients with nephrolithiasis is not necessary. Nephrolithiasis, defined as one or more stones in the kidney, affects more than 6% of the general population . The incThe exact cause of renal stone formation remains unclear. Various risk factors have been proposed, including chronic kidney disease, poor hydration, increasing age, obesity, diabetes mellitus, warm climate, and high animal protein intake , 4, 9. ASialolithiasis is a common stone disorder of the salivary gland or duct that causes swelling or pain in the face or neck by obstructing the discharge of saliva . The annPatients with nephrolithiasis are not routinely examined for stones in other organs. However, because salivary stones are mainly composed of calcium carbonates and calcium phosphates,  some invThis study aimed to evaluate whether nephrolithiasis is a risk factor for sialolithiasis using a large, nation-wide population-based cohort. study. A nephrolithiasis and control group were matched 1:4 for age, group, sex, region of residence, income group, and past medical histories. To identify the causal relationship between nephrolithiasis and sialolithiasis, patients with sialolithiasis diagnosed before nephrolithiasis were excluded from the study .The ethics committee of Hallym University (2014-I148) approved this study. Written informed consent was exempted by the Institutional Review Board.This national cohort study relies on data from the Korean Health Insurance Review and Assessment Service—National Sample Cohort (HIRA-NSC). The Korean National Health Insurance Service (NHIS) selects samples directly from the entire population database to prevent non-sampling errors. Approximately 2% (one million) of the total number of individuals were selected from the Korean population (50 million). This selected data can be classified into 1,476 levels  using randomized stratified systematic sampling methods via proportional allocation to represent the entire population. After data selection, the appropriateness of the sample was verified by a statistician who compared the data from the entire Korean population with the sample data. The details of the methods used to perform these procedures are provided by the National Health Insurance Sharing Service . This coBecause all Korean citizens are recognized by a 13-digit resident registration number from birth to death, population statistics can be determined using this database. All Koreans must enroll in the NHIS, and all Korean hospitals and clinics use the 13-digit resident registration number to register individual patients in the medical insurance system. Therefore, the risk of overlapping medical records is minimal, even if a patient moves from one place to another. Moreover, all medical treatments in Korea can be tracked without exception using the HIRA system.We identified all participants diagnosed with nephrolithiasis  among the 1,125,691 individuals with 114,369,638 medical claim codes and selected those who were treated ≥ 2 times . These participants were followed-up for up to 12 years. Sialolithiasis was diagnosed according to the ICD-10 codes (K115), and we again selected those who were treated ≥ 2 times. From 2002 through 2013, 973 sialolithiasis cases were selected. Cases involving a single visit to a clinic were excluded to reduce false positives.The nephrolithiasis patients were matched 1:4 with participants (control group) who were not diagnosed with nephrolithiasis between 2002 and 2013. The control group was selected from the mother population . Matching was for age, group, sex, income group, region of residence, and past medical histories . To prevent selection bias when selecting the matched participants, the control members were sorted from first to last using a random number order. It was assumed that the control participants were involved at the same time as the matched nephrolithiasis participants (index date). We excluded control patients who died before the index date and participants in both groups with a history of sialolithiasis before the index date. Seventeen participants were excluded from the nephrolithiasis group together with an additional 52 participants for whom we could not find adequate matches. Finally, 24,038 nephrolithiasis patients were matched with 96,152 controls . These iAge was divided into 5-year intervals: 0–4, 5–9, 10–14…, and 85+ years old. A total of 18 age groups were defined . Income The medical histories of participants were evaluated using ICD-10 codes. For accuracy of diagnosis, hypertension (I10 and I15), diabetes (E10-E49), and dyslipidemia (E78) were included if the participants were treated ≥ 2 times, and ischemic heart disease I24 and I25) and cerebral stroke (I60-I66) if the participants were treated at least once. Depression was defined as F31 (bipolar affective disorder) through F39 (unspecified mood disorder) and individuals were included if they were treated ≥ 2 times by a psychiatrist. Chronic obstructive pulmonary disease (COPD) was defined as previously [ and I25 The chi-square test was used to compare rates of general characteristics in the nephrolithiasis and control groups. To analyze the hazard ratio of nephrolithiasis to sialolithiasis, a Cox-proportional hazard model was used. In this analysis, crude (simple) and adjusted models  were used. For the subgroup analysis, we grouped the participants by age  and sex . Two-tailed analyses were conducted, and P-values less than 0.05 were considered to indicate significance. The results were analyzed using SPSS v. 21.0 .The distribution of age groups (3 subgroups of age), sex, level of income (categorized into 11 levels), region of residence , and incidences of hypertension, diabetes, and dyslipidemia were identical in the nephrolithiasis and control groups, since they were matched for these characteristics . Higher Crude and adjusted hazard ratios (HR) of nephrolithiasis for sialolithiasis were not statistically significant. The adjusted HR of nephrolithiasis for sialolithiasis was 0.81  and hence its high statistical power. The study represents the whole population of South Korea, because every citizen has to join the public medical insurance scheme. This is the second study to evaluate the association between sialolithiasis and nephrolithiasis using a public population database. In our study, the participants were followed for a long period, with a maximum of 12 years. Another advantage of this study is that comprehensive medical records were available for every participant, which enabled us to adjust for confounding factors.This is the first study using a public national database to report a lack of association between the incidence of nephrolithiasis and sialolithiasis. However it has several limitations. First, it was not a randomized clinical trial. However, we matched each nephrolithiasis patient with controls adjusting for age, sex, region of residence, medical disease including hypertension, diabetes, and dyslipidemia. Also, it is difficult to perform a randomized clinical study with a long follow-up period. Second, data on dietary habits, climate, and body-mass index were not available. Third, the participants were all Koreans, and it is well known that stone disease differs between ethnic groups . ConfirmWe found no evidence that nephrolithiasis is associated with an increased risk of sialolithiasis. We suggest that whereas nephrolithiasis is accompanied by high concentrations of calcium, uric acid, citrate, and oxalate in the urine, sialolithiasis is a multifactorial disease associated with chronic sialadenitis, salivary contents, and the anatomy of the salivary duct system. We propose that routine evaluation for sialolithiasis in all patients with nephrolithiasis is not necessary.S1 Table(DOCX)Click here for additional data file.


In summary, statin use is associated with a decreased incidence rate of cirrhosis and is most pronounced in Eastern countries but also in Western countries.Hepatitis B and hepatitis C are leading causes of chronic liver disease, particularly cirrhosis. Recently, several studies have observed that statins have an inverse relationship with cirrhosis in hepatitis B or C patients. However, no published meta-analysis studied the protective effect of statins on cirrhosis. Thus, we conducted a systematic review and meta-analysis of published observational studies to better understand the relationship between statins and the risk of cirrhosis. Relevant studies were identified by searching PubMed, EMBASE, and ISI Web of Science for articles published before April 2017. The Newcastle-Ottawa Scale was used to evaluate the quality of the included studies. Six cohort studies, including 38951 cases of cirrhosis in 263573 patients with hepatitis B or C, were identified to investigate the relationship between statins and the risk of cirrhosis. The Newcastle-Ottawa Scale scores for the included studies ranged from 6 to 9, with four high-quality studies and only two of medium quality. The use of statins was associated with a significant 42% reduction in the risk of cirrhosis, without obvious heterogeneity. In addition, this protective effect was more obvious in Asian countries. Moreover, dose-response analysis suggested each additional 50 cumulative defined daily doses (cDDD) of statins decreases the risk of cirrhosis by 11% (odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.86–0.93,  Globally, approximately 130–170 million people have hepatitis C virus infection, which is equivalent to 2% of the world's population , 5; MoreStatins are a major cholesterol-lowering drug that has been used to prevent and treat various cardiovascular diseases. Recently, other potential benefits of statins have attracted increasing attention worldwide. For example, studies have indicated that statins can decrease the risk of some cancers, including prostate, colorectal, lung, breast and liver cancers –15. In aFigure The main characteristics of the included studies are listed in Table 2 = 31.9%; p = 0.142). These results are shown in Figure Six cohort studies –26 were 2 = 58.0%)  Table .p = 0.001) .No testing for funnel plot asymmetry was performed because of the restricted number of included studies in the analysis  was performed for a more comprehensive assessment in our current meta-analysis. The cumulative Z-curve has crossed the monitoring boundaries already, demonstrating that our results were based on sufficient evidence. This finding revealed statin use were strongly associated with cirrhosis risk Figure .Although published meta-analyses suggested a protective association between statin use and risk of hepatocellular carcinoma –29, no pOur study only demonstrated an association between the use of statins and a reduced risk of cirrhosis; the data cannot establish a causative role for statins in this regard. However, if such a causative role is present, possible mechanisms could be the following. First, statins can inhibit the expression of fibrogenic cytokines such as connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF) and transforming growth factor-b (TGFb), which play a critical role in the development of cirrhosis –32. SecoOur study has several strengths. First, it is the first to explore the dose–response relationship between statin use and the risk of cirrhosis in hepatitis B or C patients. Therefore, this may provide insight into the relationship between the use of statins and the risk of cirrhosis. Second, we performed subgroup and sensitivity analyses to determine which factors affect the risk. Third, most of the studies included in our meta-analysis were of high quality. Additionally, the studies included in the meta-analysis were cohort studies, which are not prone to generate recall and selection biases. All of these characteristics make the conclusions of our study more convincing.There are several limitations that we must consider. First, there are many types of statins, including atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin, and pitavastatin. However, we failed to obtain information about the use of other types of statin, which might have an influence on the final results. Second, the outcome that we observed was an association, which is subject to confounding bias. Although we considered several adjustment factors, there remain many potential adjustment factors that are unknown, such as the cholesterol level, the triglyceride level, or other over-the-counter drug use, which are closely related to the development of cirrhosis. In addition, we failed to obtain information about antiviral treatment in patients with HBV or HCV, which could have influenced the development of cirrhosis. Third, only 6 studies were included in our article, this puts the meta-analysis at high risk of publication bias. Additionally, Studies with different outcomes are combined which leads to the concern of heterogeneity in the meta-analysis. For example, in Simon 2015 , the outIn summary, our meta-analysis indicated that the use of statins is associated with a 42% lower risk of cirrhosis in hepatitis B or C patients. Moreover, this protective effect is more obvious in Asian countries. However, more prospective studies and basic research are still urgently needed to further validate the association between the use of statins and the risk of cirrhosis as well as the potential mechanisms.We searched published reports in the PubMed, EMBASE and Web of Science using the following keywords: (“statin* OR atorvastatin OR cerivastatin OR fluvastatin OR lovastatin OR pravastatin OR rosuvastatin OR simvastatin OR pitavastatin”) and (“cirrh* OR fibro*”). The initially relevant studies were identified up to April 2017, with no restrictions on the language of publication. We have extra data through contacting the original researchers.The eligibility criteria were as follows: study design (case control or cohort); exposure factor statin and outcome cirrhosis or fibrosis; and odds ratio (OR)/risk ratio (RR) values and corresponding 95% confidence intervals (CIs) for different categories of statin use available or sufficient information provided to enable the calculation of these variables. If two studies reported the same data, we selected the study with the larger sample.Two researchers (JPX and YQW) independently extracted the required information from the selected reports in a standardized manner. We collected the following information from each article: year of publication, first author's name and country of origin, study design (case control or cohort), number of participants , duration of follow-up, sources of controls, comparison of exposure levels, potential adjusted confounding variables, OR/RR values and 95% CIs for different categories of statin use. To assess the dose–response, we also collected the number of case and person-years for each category of statin use.We used the Newcastle-Ottawa Scale  to evaluWe assessed the relationship between statins and cirrhosis using OR/RR values and the corresponding 95% CIs. When the results provided were for multiple groups with the use of statins with OR or RR values and corresponding 95% confidence intervals, we combined them to obtain a single OR/RR value and corresponding 95% CI . We treap value for the non-linear dose-response relationship was calculated by testing whether the coefficient of both the second and the third spline was zero [To enable the meta-analysis of the dose–response, we extracted the number of cases and person-years and RRs with variance estimates for at least three quantitative exposure categories from each study. If the studies did not provide these data, we required sufficient information to calculate them. For dose–response analysis, we used the midpoint of statin use in each category as the dose of statin use. If the highest category was open ended, we set the midpoint of the category at 1.5 times the lower boundary; if the lowest category was open ended, we set the lowest boundary at zero . We obtawas zero . Greenlawas zero , 42, andwas zero , 44.2 to assess heterogeneity between studies and defined low, medium, and high heterogeneity as 25%, 50%, and 75%, respectively [We used Iectively . If p waectively , Egger'sectively  and funnectively .We also performed subgroup analyses by geographic area, number of cases, study quality, and whether alcohol intake, smoking, body mass index or diabetes was adjusted for in the models. Sensitivity analyses were performed by changing the pooling model (random-effects model or fixed-effects model) and excluding studies that were not eligible for dose–response analysis. Sensitivity analysis was also performed to assess the effect of every study on the summarized estimate by sequentially excluding one study in one turn.All statistical analyses were performed using STATA version 12.0 (Stata).Random error can mislead results in meta-analyses. The random error risk may increase remarkably because of multiple looks on accumulating evidence when new trials emerge . To obta


The prevalence of overweight and obesity in children has risen greatly worldwide. Diet and poor physical activity are the two risk factors usually examined, but epidemiological evidence exists suggesting a link between sleep duration and overweight/obesity in children. The aim of this study was to describe the relationship among body mass index (BMI), diet quality, physical activity level, and sleep duration in 690 children attending the 5th grade in primary schools (9–11 years old) in the city of Parma  involved in the Giocampus educational program. This was achieved through (i) measuring anthropometric data to compute body mass index; (ii) administering a food questionnaire to evaluate adherence to the Mediterranean Diet (KIDMED score); and (iii) administering a lifestyle questionnaire to classify children physical activity level (PAL), sleep duration, and school achievement. A highly significant negative association was found between BMI and sleep hours. Moreover, there was a significant positive association between PAL and KIDMED scores. No evidence was found of association between BMI and PAL, nor between BMI and KIDMED score. Data from this study established that BMI is correlated to gender and sleep duration, defining sleep habits as one of the factors linked to overweight and obesity. The incidence of overweight and obesity is increasing in all age groups worldwide. In Italy, overweight or obesity prevalence in children reach 35% in some regions, an extremely high level considering that obesity is high risk exposure for future health conditions ,2. In paFor all these reasons, it is paramount to create a surveillance system for monitoring the actual incidence of overweight and obesity in children and for defining the relative contribution of lifestyle habits . Moreover, it is important to educate children about a healthy lifestyle, explaining the importance of a balanced diet, regular physical activity, and adequate sleep duration . In thisIn the state primary schools in the city of Parma , an educational school program named “Giocampus” has been created for improving the wellbeing of future generations through healthy eating education and promotion of physical activity. An integrated “learning through playing” approach for delivering nutritional education has been successful in improving children’s knowledge about healthy foods and a healthy lifestyle . ProfessThe aim of this study was to describe the relationship among body mass index (BMI), adherence to the Mediterranean diet (MD), physical activity level (PAL), and sleep duration in school-aged children attending the Giocampus program.The study was carried out during the 2015–2016 school years in the city of Parma , in primary schools participating to the Giocampus program. All the students enrolled in the fifth grade (9–11 years old) were asked to participate in this observational study, through letters sent to the schools. Before acceptance, school principals, teachers, and parents were fully informed about the study protocol and the methods of assessment. Data for each child were collected on the same day during school hours by two trained researchers through (i) measuring anthropometric data; (ii) administering a diet questionnaire aimed at defining the adherence to the MD; and (iii) administering a lifestyle questionnaire allowing classification of children PAL, sleep duration, and school achievement. The two questionnaires were administered directly to children.The study was performed according to the Declaration of Helsinki and was approved by the Ethical Committee of the University of Parma (n5348-15/02/16).Anthropometric measurements were collected in the morning, during the physical activity class, ensuring privacy for each child, and following the WHO guidelines . Body weAdherence to the MD was assessed through the Mediterranean Diet Quality Index for children and adolescents (KIDMED) . The KIDAccording to the Italian national survey on children lifestyle , the PALSleep habits were explored in terms of sleep duration and sleep pattern by asking about the wake up time in the morning and the time children went to sleep, for both weekdays and weekend days. Total sleep time was calculated in hours as the difference between bedtime and wake up time for weekdays and weekend days, and as the average weighted duration using the equation: (weekday time × 5 + weekend day time × 2)/7.On the basis of the National Sleep Foundation recommendations for school-age children , sleep dIn addition, sleep pattern was defined using the median value of the total week average sleep-wake schedule and classified as early bed/early rise (EE) (before 22:04 and before 07:38), early bed/late rise (EL) (before 22:04 and after 07:38), late bed/early rise (LE) (after 22:04 and before 07:38), or late bed/late rise (LL) (after 22:04 and after 07:38) ,26. School performance was assessed by asking the average grade (across subjects) of the current school year as a number, since in Italy school grades could range between 0 (very poor) and 10 (outstanding). In addition, child response was classified in three categories: mostly 10 and 9 (excellent-very good level), mostly 8 and 7 (good-very satisfactory level), and mostly 6 or less (satisfactory-poor level). All data were analyzed using descriptive statistics. Continuous variables were expressed as mean ± standard deviation (SD) of the total samples and by gender groups, BMI groups, or adherence to the MD groups. Categorical variables are presented as absolute frequencies and percentages of the total in the sample of respondents and by BMI groups or adherence to the MD groups.t-test was used to compare continuous variables between gender or BMI groups, while one-way ANOVA with Bonferroni post hoc test was used to compare among adherence to the MD groups, once the equality of variance was assessed by using the Levene’s test. A Pearson chi-square test was performed to compare categorical variables between genders, BMI groups, and adherence to the MD groups.The Kolmogorov–Smirnov test was applied to assess the normality of data distribution. The Student ®, version 24.0, IBM, Chicago, IL, USA), with the significance set at p < 0.05.The statistical analysis was completed through the Statistical Package for the Social Sciences . In addition, 21 pupils did not give their verbal consent to participate or were absent during the assessment day. A total of 690 children, 357 females (52%) and 333 males (48%), with a mean age of 10.8 ± 0.4 years old, correctly completed all study requests. Children characteristics for the total sample and by gender are presented in p = 0.019). In general, children had a medium adherence to the MD even by gender, with females being more adherent to the principles of the MD (p = 0.034). On the other hand, gender frequencies appear to differ by PAL , which was representative of a medium/high active lifestyle for both genders. According to the school-age children recommendations, children slept the recommended hours per night (9–11 h), and the sleep duration was found to be higher in females . School achievement was similar between genders, showing a good school performance of participants. No differences were found for weight and height between genders. The mean BMI corresponded to a normal weight status defined through the IOTF gender- and age-related cut-offs for both genders, despite its being higher in males , sleep duration , and school achievement categories , while they were similar for adherence to the MD, physical activity level, and sleep pattern. In addition, children in the under-normal weight group slept on average more hours per night (p = 0.005), and similar results were observed considering only weekdays or weekend days . Irrespective of gender, 500 children (72.5%) had a low or normal weight, while 190 children were overweight-obese . The two2 = 8.5, df = 2, p = 0.015), MD and physical activity level , MD and school achievement categories . Children with a low adherence to the MD had also a lower mean sleep duration (p = 0.010) and a lower sleep time during weekdays (p = 0.002). In relation to dietary habits, as shown in Consistently with their adherence to the MD, children showed positive eating habits, with only small variations registered by gender. The KIDMED questionnaire responses to each single question for the total sample and by gender are presented in Fruit and fruit juices were consumed daily by 83% of children, 48% had a second portion every day, and 35% ate nuts regularly. In addition, 73% of children had fresh or cooked vegetables regularly once a day, and 44% ate more than one portion of vegetables each day. In relation to protein-based food, 47% of participants ate fish regularly and 53% had pulses more than once a week. Pasta or rice was consumed almost every day by 84% of children. Almost 90% of children had breakfast regularly, 62% consumed cereals or grains for breakfast, 74% milk or dairy products, and 60% commercially baked goods or pastries. In addition, 36% ate two yoghurts and/or some cheese daily, and 88% used olive oil as a condiment when eating at home. Considering unhealthy habits, only 7% of students went more than once per week to a fast food restaurant, and 26% had sweets and/or candy several times every day.This study describes the relationship among body mass index, diet quality, physical activity level, and sleep duration in a sample of healthy children (aged 9–11 years) attending an educational school program in Parma, Italy.The amount of children classified as overweight or obese was 28%, a slightly lower percentage than the value (29%) observed in the region, where the city of Parma is located (Emilia-Romagna) . In turnIn our study, children showed a medium adherence to the MD, with females significantly more faithful to the principles of the MD, showing a higher attention towards healthy behaviors. However, among 33 studies analyzing gender differences in MD adherence, only 7 studies were able to significantly spot it, and 6 out of 7 reported a higher adherence in girls . In the The detailed analysis obtained from each single question of the KIDMED questionnaire showed positive dietary behaviors for breakfast, fruit, vegetable, and olive oil consumption. However, some other aspects can still be improved through specific educational interventions, targeted for example to promoting fish, pulse, and nuts consumption, the intake of which is lower than the national recommendations, consistently with results from other Italian surveys ,27. No eA significant association was observed between MD scores and PAL. This result is aligned with the findings of 14 out of 17 studies found in the literature and investigating the association of MD adherence with lifestyle aspects in children and adolescents . Our stuNo evidence was found of any association between BMI and PAL. In contrast, a highly significant negative association was found between BMI and sleep hours, although more than 76% of children declared sleeping the recommended amount of hours per night. Moreover, children with a lower sleep duration were also characterized by a low adherence to the MD, while children with a medium or high adherence to the MD slept for a similar number of hours, considering both mean and weekdays sleep quantity. These finding are aligned with results from the study by Ferranti and colleagues , where sIn our study, we did not find any association between sleep patterns and overweight/obesity in agreement with Ferranti and colleagues . HoweverFinally, both high adherence to the MD and normal body weight status seem to be correlated to high school achievement, suggesting a link between healthy lifestyle and academic performance. Recently, Tonetti and colleagues  found thThe main limitations of this study are linked to the biases inherent in the use of self-reported data, such as dietary habits and physical activity level. Besides, non-response bias shall also be considered a limitation due to the fact that the sample of respondents might not be representative of the entire potential population, and the lack of information on the non-response children (33%) could not allow bias corrections. Another limitation is that children lifestyle behaviors are affected by parental habits, which were not investigated in the present study.In conclusion, this study investigated lifestyle behaviors of a sample of primary school Italian children who were enrolled in the fifth and last year of the Giocampus school program, in Parma, Italy. The prevalence of overweight and obesity was lower in this group when compared to both the regional and national situations. In addition, the adherence to the MD and the PAL were higher than the ones reported in nationwide surveys, suggesting that the Giocampus school programme may represent a relevant contribution to the attainment of healthy lifestyles in children. Additionally, the high/very high mean amount of sleep hours highlighted a healthy lifeslyle pattern and, interestingly, was negatively and significantly associated with body weight. Based on these observations, the prevention of child obesity requires a multidisciplinary approach that considers not only physical activity and a healthy diet but also great care in defining sleeping habits. Promoting virtuous sleep behaviors may represent an important and relatively low-cost strategy for reducing the incidence of childhood obesity.Further studies are recommended to better understand the role of sleep duration and sleep related behaviors in child energy balance.


Background: Benzodiazepines are driving-impairing medicines (DIM). This study presents current consumption of dispensed benzodiazepines in the Spanish general population, with a focus in pattern of use and concomitant medicines consumed with.Methods: A population-based registry study was carried out to assess the year-2016 granted benzodiazepines dispensation in Castile and León. Weighting was performed to obtain the adjusted benzodiazepine consumption for licensed drivers according to age and gender using our national drivers' license census data.Results: Benzodiazepines were used by 15.38% of the general population and 10.97% of drivers. Nearly 2% of the population and more than 1% of drivers took these medicines every day. The amount consumed (until 3 or more benzodiazepines per day) and concomitant use of other DIM were also higher. Women were the most frequent consumers, and anxiolytic use was usual. Consumption increases with age, but there were differences between men and women drivers from 60 years old.Conclusions: The current use of benzodiazepines must serve to awareness of the healthcare personnel, patients, and authorities on their risks, above all on the road safety. Road accident injuries, and death and disability that can cause, are important concerns for authorities, healthcare personnel, and drug developers. Promoting good practice related to addressing key behavior risk factors such drink and driving, the use of motorcycle helmets, or seat-belts and child restraints, are being done worldwide WHO, . In addiBenzodiazepines are typical and well-known DIM, and there is a demonstrated relation between such and road accidents , benzodiazepines are classified as anxiolytic (N05BA) or hypnotic (N05CD), and this distinction was taken into account for the analysis. Our local ethics committee  approved the study protocol (Reference number PI 17-646).As previously made  the year-2016 benzodiazepine consumption, (2) acute (1–7 days), sub-acute (8–29 days) and chronic use (≥30 days) of benzodiazepines during the year 2016, (3) the year-2016 daily use of benzodiazepines, and (4) concomitant use of other DIM with benzodiazepines during the year 2016. Ethics Review Board approval was obtained .t-test, and those between categorical variables using Pearson's chi-squared. The level of significance was set at p ≤ 0.05. All statistical calculations were made by using the Statistical Package for the Social Sciences .Values obtained are presented, either as percentages with their 95% confidence interval (95% CI) or as means accompanied by their standard deviations (SD). Differences between continuous variables were calculated using Student's per day and 2 or more molecules per day were dispensed, respectively, to daily and non-daily users . Almost one quarter used also opioids , other analgesics and antipyretics , or antipsychotics , and one fifth used anti-epileptics . Other DIM were also used, but less frequently  and the published literature on benzodiazepine consumption  is becoming widely recognized, as they are directly affected in decisions on what medicine and at what doses are needed for treating a given disease . Nevertheless, other psychoactive medications could be relevant in the context of minor surgery procedures, endoscopy, etc. when patients are discharged after completed such procedures. In addition, the effect of herbal products that may be consumed in combination to benzodiazepines is not considered. Herbal sedatives have been used all over the world to treat insomnia and anxiety for thousands of years. The problem of consumption of such products may be greater in developing countries (WHO, Our study has limitations. Benzodiazepines dispensation cannot be considered as an equivalent to benzodiazepine consumption, as beneficiaries of our health system could having not consumed such medicines. Although a minority, both hospital-dispensed and over-the-counter medicines are not included in the data presented here. In our opinion, little changes are expected with the inclusion of this information. Our results are based on almost all benzodiazepines consumed, as our public health system dispensed more than 95% of the total amount consumed (Junta de Castilla y León; Instituto Nacional de Estadísticaies WHO, , and higies WHO, . TherefoOur study shows that benzodiazepines are frequently used. Nearly 2% of the population and more than 1% of drivers took these medicines every day. The amount consumed and concomitant use of other DIM were also higher. Women were the most frequent consumers, and anxiolytic use was usual. Consumption increases with age, but there were differences between men and women drivers from 60 years old.These findings that are consistent with available evidence, must serve to inform the healthcare personnel, above all those who may be unaware of the problem, as well as patients, their families, the population at large, and authorities on the current use of benzodiazepines.FJA developed the hypothesis and study design. EG-A and PC-E performed statistical analysis. FH-G and FJA drafted the manuscript. All authors have given final approval for this paper to be published.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.


Background: Higher socioeconomic status is known to decrease the risk for poor mental health overall. However, African American males of higher socioeconomic status (SES) are at an increased risk for having a major depressive episode (MDE). It is not known whether perceived discrimination (PD) explains this risk. The current study used nationally representative data to explore the role of PD in explaining the association between high-SES and having MDE among African American men. Methods: The National Survey of American Life (NSAL), 2003, included 4461 American adults including 1271 African American men. SES indicators  were the independent variables. 12-month MDE measured using the Composite International Diagnostic Interview (CIDI) was the outcome. Age, gender, and region were the covariates. PD was the potential mediator. For data analysis, we used logistic regression. Results: Among African American men, household income was positively associated with odds of 12-month MDE. The positive association between household income and odds of MDE remained unchanged after adding PD to the model, suggesting that PD may not explain why high-income African American men are at a higher risk of MDE. Conclusions: Perceived discrimination does not explain the increased risk for depression among African American males of higher SES. Future research should explore the role of other potential mechanisms such as stress, coping, social isolation, and/or negative social interaction that may increase psychological costs of upward social mobility for African American males. Minorities’ Diminished Return Theory [In contrast to the mainstream theoretical  and empin Theory ,13.The seminal theoretical work by Link and Phelan , MirowskMinorities’ Diminished Return Theory [Minorities’ Diminished Return Theory, extensive empirical research has shown that it is not African Americans, but Whites whose health is closely affected by SES [n Theory ,13, suggn Theory ,24 and mn Theory ,26,27 thd by SES ,13,27.Minorities’ Diminished Return Theory [Ironically, and in a counterintuitive pattern  ,6,7, Afrn Theory ,13, it in Theory ,3,4.For at least two reasons, this study proposes perceived discrimination (PD) as an underlying mechanism for the positive association between SES and risk of depression in African American males. First, high SES is associated with higher, rather than lower, PD for African American males ,7. This To extend our previous work in this area , and to National Survey of American Life (NSAL) is one of the most comprehensive and updated mental health surveys of Blacks in the U.S. The NSAL was conducted as a component of the Collaborative Psychiatric Epidemiology Surveys (CPES) by University of Michigan, Ann Arbor ,43.NSAL used a national household probability sampling strategy of Black adults to generate representative statistics of Black Americans. The NSAL sample included 3570 African Americans. All participants were age 18 or older. The NSAL sample was composed of individuals who were residing in the U.S. at the time of the study. More detailed information regarding the NSAL sampling is available elsewhere . The anaIn the NSAL, all interviews were all conducted in the English language. All face-to-face interviews used a computer-assisted personal interview (CAPI) format. CAPI is an interview model in which respondents use computers to provide answers to the questionnaire. CAPI improves data quality in long and complex surveys . The NSAThe current analysis used data on demographic factors , SES indicators , and 12-month MDE.Demographics. This study treated age as a continuous variable.Socioeconomic Status (SES). All measured using self-reported data, four SES indicators were entered to the current study: education attainment, household income, marital status, and employment status. Educational attainment , employment status , and marital status  were all dichotomous variables. Household income was operationalized as a continuous measure and presented as income in increments of 1000 U.S. dollars.Major Depressive Episode (MDE). NSAL used the Composite International Diagnostic Interview (CIDI) to measure 12-month MDE, which reflects experience of a major episode of depression which lasted two weeks or more during the last 12 months. Main symptoms used to diagnose MDE in our study are depressed mood , and anhedonia (lack of interest or pleasure) for more than two weeks. MDE is not a score but a categorical diagnosis, so it is not based on a certain threshold. This diagnosis is based on the Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) [(DSM-IV) . CIDI, a(DSM-IV) . CIDI ba(DSM-IV) ,46,47,48(DSM-IV) ,50,51.Perceived Discrimination. Perception of daily racial discrimination was measured using the perceived discrimination instrument developed by Williams et al., 1997 [l., 1997 . The insnever” (coded as 0), “less than once a year” (coded as 1), “a few times a year” (coded as 2), “a few times a month” (coded as 3), “at least once a week” (coded as 4), and “almost every day” (coded as 5). A sum score for the 10 items were calculated, with a potential range from 0 to 50. The internal reliability of the measure was 0.93.The measure specifically focuses on daily racial discrimination that represents instances of discrimination that involve minor, rather than major, events and episodes that respondents recurrently face in their daily lives. Participants were asked about frequency of 10 types of unfair treatment that had occurred in their everyday lives. Response scale included “The NSAL study protocol received Institutional Review Board (IRB) approval from University of Michigan, Ann Arbor (B03-00004038-R1). Respondents were financially compensated for participating in the study. Written informed consent was provided by all participants.p values are based on comparison of weighted statistics.To accommodate the NSAL-Adults survey design, Stata 13.0  was used for data analysis. Design-based variance and standard errors re-were re-estimated using the Taylor series approximation techniques. As a result, means and percentages reported in this study were representative of the U.S. population. Weights were also used for all inferences, so our Model 1 did not include PD. Model 2 included PD. In our models, SES characteristics were the independent variables, MDE was the dependent variable, demographics and region were covariates, and PD was the mediator. Odds ratio (OR) and 95% confidence interval (CI) were reported. p values less than 0.05 was considered statistically significant.Two sub-population survey logistic regressions models were estimated for multivariable data analysis. This study included 1271 African American men. These results suggested that PD may not mediate the effect of income on odds of MDE among African American men.The current study was conducted to test whether PD explains the positive association between income and risk of MDE in male African Americans. The findings did not suggest that higher PD is why high-SES African American males are at a higher risk of MDE.This is not the first study on the risks associated with high SES in African American males. It is also not the first study on the link between SES and depression by the intersection of race and gender ,53. In tThis study is, however, one of the first to explore the role of PD in explaining high risk of MDE in high-SES African American males. Previous theoretical work has proposed PD as a potential underlying mechanism for Blacks’ diminished return of SES  ,13. ThisThese findings should not be considered against the overall protective effects of SES on health ,59,60,61In this study, PD was a risk factor for MDE, regardless of covariates. Literature is well-established that PD reduces both physical and mental health ,70,71,72These results may have implications for theory as well as policy. Most current conceptual frameworks ) have exclusively focused on the protective effects of high SES ,58. BeinAs the current study failed to show PD as an underlying mechanism for high risk of MDE for high SES Black men, other mechanisms should be explored in future research. Several mechanisms are involved in the link between SES and health. SES resources enable individuals to escape harmful exposures ,58. IndiOur study is not free of limitations. First, SES measures were not ideal. We defined income as continuous dollar amounts, which does not account for the differential value of the same income based on regional/geographic location of residence. For example, one thousand dollars of additional income does not similarly change financial and/or social statuses of individuals residing in New York and Detroit. Employment status was coded as a dichotomous variable . This over-simplified measure fails to capture underemployment, as well as part-time versus full-time employment. Income was also treated as a continuous measure. Educational attainment is measured with a dichotomous variable . This categorization ignores differences in the educational level of individuals with a high school diploma from people who have achieved a doctorate degree. We used dichotomous measures of education and employment to reduce the co-linearity between various indicators of SES, particularly with income. Second, the study may have omitted variables such as receiving treatment for depression and other psychiatric disorders. We did not control for a wide range of relevant covariates, such as health behaviors, physical health, and history of depression diagnosis by a health care provider. Despite these limitations, using a nationally representative sample with large sample size is a strength of our study.The current study failed to show PD as a mediator for high risk of MDE in high-SES African American males. Factors other than PD may be studied to understand why high-SES African American males are at high risk of depression. Future research should examine the role of additional psychological and social costs of upward social mobility, stress , negative social interaction, coping, social isolation, or institutional racism to explain the high risk of MDE in African American males. Findings: NSAL is funded by the National Institute of Mental Health . Other funding includes support from the Office of Behavioral and Social Science Research (OBSSR) at the National Institutes of Health (NIH). University of Michigan (UM) also provided some funding for the NSAL.


Until recently, the role of factor XII (FXII) in hemostasis was not considered to be important since patients with FXII deficiency do not present with bleeding. The activation of FXII by agents including mast cells and platelet polyphosphates suggests that it may have a role in thrombogenesis. The inhibition of FXII therefore presents an option for antithrombotic therapy, and antibodies and inhibitors are already in development. Assays for FXII will be required to support these technologies, and an international standard (IS) for FXII would be useful for the development of these methods and for the clinical monitoring of patients. The purpose of this study was to develop an IS for FXII, with values for functional activity (FXII:C) and antigen (FXII:Ag). Double-spun normal plasma was pooled, filled into siliconized glass ampoules, and freeze-dried to prepare the candidate material. Data from 20 laboratories using the one-stage clotting assay were used to assign the functional activity value in units (u). The antigen value was calculated using data from eight laboratories that carried out antigen assays. Each laboratory was requested to collect two local normal plasma pools. Units of activity and antigen were calculated relative to these pools, as is usual for new coagulation factor analytes. The amount of activity or antigen in 1 ml of normal plasma from each pool was taken to be 1 unit. A total of 566 donors were used across the pools for the FXII:C study and 216 donors for the FXII:Ag study. The overall geometric mean per ampoule for FXII:C was 0.86 u and for FXII:Ag was 0.80 u. The inter-laboratory variation was 10 and 11%, respectively (expressed as the geometric coefficient of variation). Based on these data, the candidate was deemed suitable for use as an IS for FXII. In 2017, the candidate was established by the World Health Organization (WHO) Expert Committee on Biological Standardization as the WHO first IS for blood coagulation FXII, Plasma . The values assigned were 0.86 international units (IU) of functional activity (FXII:C) per ampoule and 0.80 IU/ampoule of antigen (FXII:Ag). Historically, the role of FXII in vivo was considered less important, since FXII patients do not suffer from abnormal bleeding and, similarly, FXII-deficient mice are healthy and free from bleeding disorders  is an important coagulation factor isorders . It was isorders , suggestisorders  and neutisorders  have beesyndrome , anaphylsyndrome . With thsyndrome , 8, and The processing conditions required to make a standard for FXII are the same as those required for a FXI standard, since both are contact activation factors and exposure to glass or cold results in the activation to FXIIa and FXIa, respectively. The first IS for FXI has just been replaced by the second IS due to stock depletion , so thisThe candidate material (15/180) is the same as used for the second IS for FXI, Plasma, details of which have been published elsewhere . BrieflyThe candidate material (NIBSC code 15/180) was provided to the participants as coded duplicate samples, A and B. New coagulation factor standards are assigned relative to normal plasma pools, assuming that 1 ml of plasma contains 1 unit of activity or antigen. Therefore, participants were also asked to collect fresh local normal plasma pools for use both fresh (coded P1) and subsequently frozen (coded P2) in the study, for use as the standard. NIBSC in-house studies on both FXII functional activity and FXII antigen have shown that using fresh plasma, compared to the same pool of plasma after freezing, does not produce significantly different results. Therefore, for the participants unable to collect fresh plasma pools, frozen plasma pools could be used as an alternative. Overall, the pools used to assign the functional activity contained plasma from 566 donors, and the pools used for the antigen assignment comprised 216 donors.There were 20 laboratories from 10 countries  that took part in the FXII:C assignment. Of these, there were seven clinical laboratories, four therapeutics producers, six diagnostics manufacturers, two regulatory laboratories, and one research laboratory. Eight laboratories took part in the FXII:Ag assignment. These laboratories were from Canada, Denmark, France, Germany, United Kingdom, and USA, comprising one clinical laboratory, one diagnostics manufacturer, four therapeutics producers, and two regulatory laboratories.Participants were asked to assay coded duplicates A and B against local normal plasma pools and FXII:C and/or FXII:Ag using their usual in-house methods. Laboratories were provided with a protocol for the collection of plasma pools and a separate protocol giving guidance for the randomization of samples and for sufficient replication to enable statistical analysis. Four independent assays were requested for each analyte. FXII is part of the intrinsic pathway and is measured using the APTT assay. APTT reagents contain phospholipid and an activator(s) of the contact pathway (such as ellagic acid). When used with FXII-deficient plasma, the clotting time upon the addition of calcium can be used to calculate the FXII present in a given sample, relative to a standard. All participants in the FXII:C study used one-stage clotting assays with an APTT reagent. Thirteen different APTT reagents were used across different instruments and sources of deficient plasma. The sources of APTT reagent (together with the activator and the range of activation times used) and deficient plasmas used are listed in Tables 10 transformation of the assay response was used for the FXII antigen assays and for the FXII functional assays; data from nine laboratories were transformed, with the rest not requiring transformation. The mean potencies were calculated as unweighted geometric means (GMs), and the variability between assays and laboratories is shown as the geometric coefficients of variation . In order to detect any significant outliers, the log10-transformed laboratory mean estimates were subjected to Grubbs’ test , these data were treated independently .Raw data from the participants were returned to NIBSC for parallel line analysis  with Combs’ test . ApproprThis study was carried out alongside the study on the second IS for FXI, Plasma , and thep = 0.859). Of the different APTT reagents used, there was no detectable method bias.Participants were requested to prepare two plasma pools P1 and P2) for use as fresh in two assays and as freeze-thawed pools in a further two assays. Participants who were unable to collect fresh plasma pools were asked to use two different batches of local frozen plasma pools. Results for samples A and B, the coded duplicates, were analyzed relative to P, assuming 1 unit of FXII:C content per 1 ml of plasma pool. The GM for sample A vs P was 0.86 units per ampoule, with 95% confidence limits of 0.83–0.89. The result for sample B was 0.85 units per ampoule, with 95% confidence limits of 0.82–0.89. The intra-laboratory variation ranged from 1.7 to 20.0% for sample A and 1.9 to 19.0% for sample B, with the majority being less than 10%. Overall, the inter-laboratory GCV was 10% for each analyte. This variation is to be expected given the different plasma pools used by each laboratory. The results for A and B showed no significant difference, so the results were combined to give overall results for AB per laboratory , compared to 0.81 u/ampoule (95% confidence limits of 0.75–0.87) for B against P. The inter-laboratory variation was 10.0 and 11.0% for A and B, respectively, showing acceptable agreement between laboratories. The results for A and B, which showed no significant differences, were combined to give a result for AB overall per laboratory  of the International Society on Thrombosis and Haemostasis (ISTH). Both recommended that the candidate 15/180  be used as an IS for FXII:C and FXII:Ag. In October 2017, the WHO ECBS established 15/180 as the first IS for FXII: plasma, human, with assigned values of 0.86 international unit (IU)/amp for FXII functional activity (FXII:C) and 0.80 IU/amp for FXII antigen (FXII:Ag).HW, JH, PR, and EG designed the study. HW and EG organized the study and wrote the manuscript. JH and PR analyzed 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.