Teacher-reported emotional and behavioural problems and ethnic background associated with children's psychosocial care use: a longitudinal population-based study.

Approximately, 15% of children in Western countries suffer from emotional and behavioural problems. However, not all children receive the psychosocial care they need, especially children with a non-Western background experience an unmet need for care. This might be because parents of non-Western children report a lower need for care than parents of Western children, unrelated to the actual need. This study examined the association between teacher-reported problems and psychosocial care use, independent of mother-reported problems. Further, the role of ethnic background in this association was investigated. The study sample of 9-year-old children was retrieved from the Generation R Study (N = 3084), a prospective, population-based cohort of children born in Rotterdam, the Netherlands. Teacher- and mother-reported problems were measured via questionnaire when the children were  6/7 years old. Psychosocial care use was mother-reported at the research centre when children were 9 years old (8.1%). Hierarchical logistic regressions showed significant positive associations between teacher-reported total, externalising and internalising problems and later psychosocial care use. These associations were independent of mother-reported problems. Children with a non-Western background used less care, but ethnic background did not moderate the association between teacher-reported problems and care use. Our findings suggest that teachers might have an important role, next to parents, in the identification of problems and children's access to care. This may be particularly important for non-Western children, as they use less psychosocial care than Western children, despite other research showing that they generally display higher levels of problems. Directions for future research and implications are discussed.

Contextual determinants associated with children's and adolescents' mental health care utilization: a systematic review.

Determinants at the contextual level are important for children's and adolescents' mental health care utilization, as this is the level where policy makers and care providers can intervene to improve access to and provision of care. The objective of this review was to summarize the evidence on contextual determinants associated with mental health care utilization in children and adolescents. A systematic literature search in five electronic databases was conducted in August 2021 and retrieved 6439 unique records. Based on eight inclusion criteria, 74 studies were included. Most studies were rated as high quality (79.7%) and adjusted for mental health problems (66.2%). The determinants that were identified were categorized into four levels: organizational, community, public policy or macro-environmental. There was evidence of a positive association between mental health care utilization and having access to a school-based health center, region of residence, living in an urban area, living in an area with high accessibility of mental health care, living in an area with high socio-economic status, having a mental health parity law, a mental health screening program, fee-for-service plan (compared to managed care plan), extension of health insurance coverage and collaboration between organizations providing care. For the other 35 determinants, only limited evidence was available. To conclude, this systematic review identifies ten contextual determinants of children's and adolescents' mental health care utilization, which can be influenced by policymakers and care providers. Implications and future directions for research are discussedPROSPERO ID: CRD42021276033.

Children's use of psychosocial care in a population-based longitudinal study: less likely for girls, children with a non-Western background and children with a high quality of life.

Knowledge on determinants of children's psychosocial care use is important to improve their access to care. This study examined the independent contributions of need and predisposing factors to psychosocial care use in 9-year-old children, guided by the Gateway Provider Model. Data of the Generation R Study, a prospective cohort of children born in Rotterdam, the Netherlands, were analysed using multivariable logistic regression (n = 4714). Need (quality of life, presence and type of emotional/behavioural problems) and predisposing factors (sex, ethnic background and maternal educational level) were measured using parent questionnaires at multiple time points between ages 1.5 and 9 years. Psychosocial care use was parent-reported at 9 years old (9.6% among children with Western background, 7.3% among children with non-Western background). Having emotional/behavioural problems at 5 and 9 years old was associated with more care use, while having a higher quality of life, being a girl and having a Moroccan/Turkish or other non-Western background were associated with less care use. Externalising and internalising problems, as well as several types of problems, at 5 and 9 years old were associated with psychosocial care use. Stratified analyses revealed that, in children with non-Western backgrounds, only a poorer psychosocial quality of life was associated with psychosocial care use. To conclude, girls with a Western background and children with a non-Western background were less likely to receive care compared to their peers. Children with parent-reported emotional/behavioural problems at 5 and 9 years old and decreased quality of life at 5 years old were more likely to receive psychosocial care use at 9 years old. Our findings hold relevance for preventive policies.

Quality of Life During and After Completion of Neoadjuvant Chemoradiotherapy for Esophageal and Junctional Cancer.

BACKGROUND: The course of health-related quality of life (HRQOL) during and after completion of neoadjuvant chemoradiotherapy (nCRT) for esophageal or junctional carcinoma is unknown. METHODS: This study was a multicenter prospective cohort investigation. Patients with esophageal or cancer to be treated with nCRT plus esophagectomy were eligible for inclusion in the study. The HRQOL of the patients was measured with European Organization for Research and Treatment of Cancer QLQ-C30, QLQ-OG25, and QLQ-CIPN20 questionnaires before and during nCRT, then 2, 4, 6, 8, 10, 12, 14, and 16 weeks after nCRT and before surgery. Predefined end points were based on the hypothesized impact of nCRT. The primary end points were physical functioning, odynophagia, and sensory symptoms. The secondary end points were global quality of life, fatigue, weight loss, and motor symptoms. Mixed modeling analysis was used to evaluate changes over time. RESULTS: Of 106 eligible patients, 96 (91%) were included in the study. The rate of questionnaires returned ranged from 94% to 99% until week 12, then dropped to 78% in week 16 after nCRT. A negative impact of nCRT on all HRQOL end points was observed during the last cycle of nCRT (all p < 0.001) and 2 weeks after nCRT (all p < 0.001). Physical functioning, odynophagia, and sensory symptoms were restored to pretreatment levels respectively 8, 4, and 6 weeks after nCRT. The secondary end points were restored to baseline levels 4-6 weeks after nCRT. Odynophagia, fatigue, and weight loss improved after nCRT compared with baseline levels at respectively 6 (p < 0.001), 16 (p = 0.001), and 12 weeks (p < 0.001). CONCLUSION: After completion of nCRT for esophageal cancer, HRQOL decreases significantly, but all HRQOL end points are restored to baseline levels within 8 weeks. Odynophagia, fatigue, and weight loss improved 6-16 weeks after nCRT compared with baseline levels.

Children's sugar-sweetened beverages consumption: associations with family and home-related factors, differences within ethnic groups explored.

BACKGROUND: The consumption of sugar-sweetened beverages (SSB) may contribute to the development of overweight among children. The present study aimed to evaluate associations between family and home-related factors and children's SSB consumption. We explored associations within ethnic background of the child. METHODS: Cross-sectional data from the population-based 'Water Campaign' study were used. Parents (n = 644) of primary school children (6-13 years) completed a questionnaire on socio-demographic characteristics, family and home-related factors and child's SSB intake. The family and home-related factors under study were: cognitive variables (e.g. parental attitude, subjective norm), environmental variables (e.g. availability of SSB, parenting practices), and habitual variables (e.g. habit strength, taste preference). Regression analyses were used to evaluate the associations between family and home-related factors and child's SSB intake (p < 0.05). RESULTS: Mean age of the children was 9.4 years (SD: 1.8) and 54.1% were girls. The child's average SSB intake was 0.9 litres (SD: 0.6) per day. Child's age, parents' subjective norm, parenting practices, and parental modelling were positively associated with the child's SSB intake. The availability of SSB at home and school and parental attitude were negatively associated with the child's SSB intake. The associations under study differed according to the child's ethnic background, with the explained variance of the full models ranging from 8.7% for children from Moroccan or Turkish ethnic background to 44.4% for children with Dutch ethnic background. CONCLUSIONS: Our results provide support for interventions targeting children's SSB intake focussing on the identified family and home-related factors, with active participation of parents. Also, the relationships between these factors and the child's SSB intake differed for children with distinct ethnic backgrounds. Therefore, we would recommend to tailor interventions taking into account the ethnic background of the family. TRIAL REGISTRATION: Number NTR3400 ; date April 4th 2012; retrospectively registered.

rRNA Operon Copy Number Can Explain the Distinct Epidemiology of Hospital-Associated Methicillin-Resistant Staphylococcus aureus.

The distinct epidemiology of original hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) and early community-associated MRSA (CA-MRSA) is largely unexplained. S. aureus carries either five or six rRNA operon copies. Evidence is provided for a scenario in which MRSA has adapted to the hospital environment by rRNA operon loss (six to five copies) due to antibiotic pressure. Early CA-MRSA, in contrast, results from wild-type methicillin-susceptible S. aureus (MSSA) that acquired mecA without loss of an rRNA operon. Of the HA-MRSA isolates (n = 77), 67.5% had five rRNA operon copies, compared to 23.2% of the CA-MRSA isolates (n = 69) and 7.7% of MSSA isolates (n = 195) (P < 0.001). In addition, 105 MSSA isolates from cystic fibrosis patients were tested, because these patients are repeatedly treated with antibiotics; 32.4% of these isolates had five rRNA operon copies. For all subsets, a correlation between resistance profile and rRNA copy number was found. Furthermore, we showed that in vitro antibiotic pressure may result in rRNA operon copy loss. We also showed that without antibiotic pressure, S. aureus isolates containing six rRNA copies are more fit than isolates with five copies. We conclude that HA-MRSA and cystic fibrosis isolates most likely have adapted to an environment with high antibiotic pressure by the loss of an rRNA operon copy. This loss has facilitated resistance development, which promoted survival in these niches. However, strain fitness decreased, which explains their lack of success in the community. In contrast, CA-MRSA isolates retained six rRNA operon copies, rendering them fitter and thereby able to survive and spread in the community.

A setup for synchrotron-radiation-induced total reflection X-ray fluorescence and X-ray absorption near-edge structure recently commissioned at BESSY II BAMline.

An automatic sample changer chamber for total reflection X-ray fluorescence (TXRF) and X-ray absorption near-edge structure (XANES) analysis in TXRF geometry was successfully set up at the BAMline at BESSY II. TXRF and TXRF-XANES are valuable tools for elemental determination and speciation, especially where sample amounts are limited (<1 mg) and concentrations are low (ng ml(-1) to µg ml(-1)). TXRF requires a well defined geometry regarding the reflecting surface of a sample carrier and the synchrotron beam. The newly installed chamber allows for reliable sample positioning, remote sample changing and evacuation of the fluorescence beam path. The chamber was successfully used showing accurate determination of elemental amounts in the certified reference material NIST water 1640. Low limits of detection of less than 100 fg absolute (10 pg ml(-1)) for Ni were found. TXRF-XANES on different Re species was applied. An unknown species of Re was found to be Re in the +7 oxidation state.

Do children report differently from their parents and from observed data? Cross-sectional data on fruit, water, sugar-sweetened beverages and break-time foods.

BACKGROUND: Reliable assessment of children's dietary behaviour is needed for research purposes. The aim of this study was (1) to investigate the level of agreement between observed and child-reported break-time food items; and (2) to investigate the level of agreement between children's reports and those of their parents regarding children's overall consumption of fruit, water and sugar-sweetened beverages (SSB). METHODS: The children in this study were 9-13 years old, attending primary schools in Rotterdam, the Netherlands. Children were observed with respect to foods brought for break-time at school. At the same day, children completed a questionnaire in which they were asked to recall the food(s) they brought to school to consume during break-time. Only paired data (observed and child-reported) were included in the analyses (n = 407 pairs). To determine each child's daily consumption and average amounts of fruit, water and SSB consumed, children and their parents completed parallel questionnaires. Only paired data (parent-reported and child-reported) were included in the analyses (n = 275 pairs). The main statistical measures were level of agreement between break-time foods, fruit, water and SSB; and Intra-class Correlation Coefficients (ICC). RESULTS: More children reported bringing sandwiches and snacks for break-time than was observed (73 % vs 51 % observed and 84 % vs 33 % observed). The overall agreement between observed and child-reported break-time foods was poor to fair, with ICC range 0.16-0.39 (p < 0.05). Children reported higher average amounts of SSB consumed than did their parents (1.3 vs 0.9 L SSB, p < 0.001). Child and parent estimations of the child's water and fruit consumption were similar. ICC between parent and child reports was poor to good (range 0.22-0.62, p < 0.05). CONCLUSION: Children report higher on amount of break-time foods as compared to observations and children's reports of SSB consumption are higher than those of their parents. Since the level of agreement between the observed break-time foods and that reported by children and the agreement of child's intake between parent and child reports are relatively weak, future studies should focus on improving methods of evaluating children's consumption behaviour or on ways on how to best use and interpret multiple-source dietary intake data. TRIAL REGISTRATION: Current Controlled Trials NTR3400 .

Large-scale feasibility of organic acids as a permanent preharvest intervention in drinking water of broilers and their effect on foodborne Campylobacter spp. before processing.

AIMS: Evaluating the effect of a commercially available organic acid water additive in conventional broiler production on Campylobacter spp. METHODS AND RESULTS: The organic acid water additive was added to the drinking water from chick housing to catching in three consecutive rearing cycles. The broiler performance data were evaluated, and the load of thermophilic Campylobacter spp. was analysed in water, feed and the environment as well as determined in caecum content and on carcasses at the abattoir according to ISO 10272:1.2-2002. The results indicated that permanent application of acidified drinking water did not have detrimental effects on production parameters or animal welfare. The quantitative results obtained at slaughter were ambiguous, but suggested a reduced carriage of Campylobacter spp. by the flock and in caecum content. Such reduction did not result in lower Campylobacter carriage of the carcasses after slaughter. CONCLUSIONS: Organic acids in drinking water of broilers can partly reduce the caecal Campylobacter spp. load, but this did not reduce carcass contamination. SIGNIFICANCE AND IMPACT OF THE STUDY: Broiler meat is a major source of foodborne campylobacteriosis. The public health would considerably benefit from controlling Campylobacter in the food chain. The addition of organic acid to drinking water of broilers can potentially lower the caecal carriage in primary production. However, in this field trial, a commercial product failed to have an impact on the bacterial load after slaughter.

Effect of increased post length due to the presence of the remaining coronal structure on the fracture strength of post-retained restorations.

This study evaluated the effects of the remaining coronal tissue and post type on the fracture strength of incisors. Sixty human maxillary central incisors were sectioned at the cemento-enamel junction or at 2 mm above this junction. The roots received cast cores and posts, fibre posts, or relined fibre posts (n = 10 each). A compressive load was applied over the cores untilfracture. In the absence of coronal structure, the fracture strength did not differ among the post types evaluated. In the presence of remaining coronal structure, the fracture strength was higher in specimens with cast cores and posts.

Total skin electron beam therapy for cutaneous T-cell lymphomas in the Netherlands: A retrospective analysis of treatment outcomes and selection for high or low dose schedule.

PURPOSE: Total skin electron beam therapy (TSEBT) is used mostly in the treatment of cutaneous T cell lymphoma. In this study we describe the results of TSEBT applied in the Netherlands using two different schedules, a conventional dose schedule of 35 Gy and a low-dose schedule of 12 Gy. We aimed to evaluate the treatment results in and compare treatment outcomes between the two treatment groups and to further define indications for both doses. METHODS: In the LUMC, Leiden, we performed a retrospective analysis of 51 patients treated with TSEBT between January 2008 and December 2018, with follow-up untill December 2019. Thirty one patients were treated with 35 Gy and twenty with 12 Gy. The dose was chosen based on the severity of skin involvement. Outcome measures were time to meaningful progression, survival, response rate and toxicity. RESULTS: Time to meaningful progression was 5.1 months with no significant differences between dose groups (P = 0.77). Overall survival was 27.4 months. Both time to progression and survival were significantly better for T2 vs T3 stage. Overall response rate was 80.4 %. Both dose groups showed improvement of symptoms. Treatment was generally well tolerated. CONCLUSIONS: Both high-dose and low-dose TSEBT offer similar results for TMP and OS. It remains unclear which patients benefit most from a high-dose schedule. We propose to use the low-dose schedule as a standard for TSEBT and use supplementary boosts or escalation to high-dose treatment for patients unresponsive to the low-dose schedule.

Moral reasoning perspectives of community pharmacists in situations of drug shortages.

BACKGROUND: Drug shortages affect health systems worldwide. Research in community pharmacy has focused on the nature, extent and impact of these shortages on patients and pharmacists. However, pharmacists' moral reasoning in situations of drug shortages has not been addressed. OBJECTIVE: To explore the moral reasoning perspectives of Dutch community pharmacists in situations of drug shortages. METHOD: An electronic survey was developed around three drug shortage scenarios with a varying impact on patient outcomes: a Contraceptive, a Parkinson's and an Osteoporosis scenario. Pharmacists rated the likelihood of nine handling options and rated and ranked 13 considerations that may have played a role therein. The considerations represented three moral reasoning perspectives (MRPs): a business orientation (BO), a rules and regulations (RR), and a professional ethics (PE) MRP. Principle component analysis (PCA) was used to investigate construct validity of the MRPs. MRP rating and MRP ranking scores measured the relative importance of the different MRPs of pharmacists in the three shortages. RESULTS: Results from 267 Pharmacists were obtained. They reported mostly similar handling in the three shortages, except for the likelihood to make agreements with prescribers or other pharmacists and regarding the decision to import a product. The PCA analysis confirmed the three MRPs that accounted for 29% of variance in the data. Both the MRP rating and especially the MRP ranking scores indicated that PE-MRP considerations were most influential on pharmacists' intended handling of the shortages. In the Contraceptive and the Osteoporosis scenarios, the relative importance of a BO-MRP was higher than in the Parkinson's scenario. CONCLUSION: Pharmacists predominantly reason with a PE-MRP when handling drug shortages. However, this perspective can be compromised when the drug shortage is perceived to have a lower impact on patient outcomes and when alternative drugs or therapy are expensive.

Weight status, energy-balance behaviours and intentions in 9-12-year-old inner-city children.

BACKGROUND: Dutch youth health care promotes four so-called energy-balance behaviours for the prevention of obesity: increasing physical activity, reducing sedentary behaviour and sugar-containing drinks, and eating breakfast. However, data on the prevalence of these behaviours and intentions to engage in them among primary schoolchildren is limited, especially for multi-ethnic, inner-city populations. The present study aimed to provide these data and explore differences according to socio-demographic characteristics and weight status. METHODS: Data on behaviours and accompanying intentions were collected using classroom questionnaires. Stature and body weight were measured by trained staff. Twenty primary schools in Rotterdam participated. Data on 1095 9-12 year olds (81.7% response rate) were available for analysis. Multiple logistic regression analyses were conducted to determine associations between behaviours (favourable or unfavourable), intentions (positive or not), gender, age, ethnicity, neighbourhood income level and weight status. RESULTS: The prevalence of being overweight was 30.4%, including 9.0% obesity. Engagement in energy-balance behaviours varied from 58.6% for outdoor play (>1 h previous day) to 85.9% for active transportation to school (day of survey). The highest positive intentions were reported for taking part in sports (83.9%), and lowest for reducing computer time (41.3%). Small differences in behaviours and intentions according to socio-demographic characteristics were found, most notably a lower engagement in physical activity by girls. Skipping breakfast and total number of energy-balance behaviours were associated with being overweight. CONCLUSIONS: The prevalence of being overweight among Dutch inner-city schoolchildren is high. A general rather than a differentiated approach is needed to improve engagement in energy-balance behaviours among inner-city schoolchildren.

Moral reasoning among Dutch community pharmacists: testing the applicability of the Australian Professional Ethics in Pharmacy test.

Background Moral reasoning competency is essential in healthcare practice, especially in situations of moral dilemmas when a professional has to choose a morally justifiable action among several suboptimal action options. The Australian Professional Ethics in Pharmacy test (PEP test) measures moral reasoning among pharmacists. In Australia three levels of moral reasoning (schemas) were measured (1) business orientation (2) rules and regulations, and (3) patient rights (i.e. most advanced schema). Objective To test the applicability of the PEP test to pharmacists working in the Netherlands. Setting Dutch community pharmacy. Methods The PEP test consists of 36 statements (items) accompanying 3 moral dilemma scenarios. It was translated into Dutch and completed by 390 pharmacists. Principle component analysis (PCA) was used to investigate construct validity and Cronbach's Alpha was used to indicate internal consistency of the Dutch version of the PEP test. The eligible grouped statements and perceived possible moral reasoning schemas were compared to the Australian findings. Main outcome measure Moral reasoning schemas. Results The PCA analysis resulted in 3 components (i.e. possible moral reasoning schemas) that together accounted 27% variance in the data. The statements that represented the moral reasoning schemas 'business orientation' and 'rules and regulations' were somewhat similar when comparing these with the statements that represented these schemas in the PEP test study. The most advanced moral reasoning schema identified in Dutch pharmacists contained different statements compared to the statements that represented that schema among Australian pharmacists. This schema was labelled 'professional ethics'. Conclusion The PEP test needs further adaptation to the Dutch pharmacy practice context: especially the statements that should reflect the most advanced moral reasoning schema, need more accurate representations of professional pharmacy ethics that guide pharmacists in the Netherlands. Moral reasoning tests for a specific professional setting or country should be developed and adapted by experts who share the same professional values and practice as the respondents.

Dependence of correlations between antibody titres and opsonophagocytosis on pneumococcal serotype and patient morbidity in pre- and post-pneumococcal vaccination states.

Pre- vs. post-vaccination changes in correlations between IgG concentrations (ELISA titres) and opsonophagocytic activity (OPA) against Streptococcus pneumoniae serotypes 6B, 14 and 23F induced by the 23-valent polysaccharide vaccine were studied in paired serum samples received from elderly individuals, haemodialysed patients and kidney transplant recipients by the Spanish Pneumococcal Reference Laboratory. The pre- and post-vaccination parameters considered were: ELISA and OPA titres and the percentage of subjects with post-vaccination OPA values above the cut-off levels; the correlations between OPA and ELISA (Spearman correlation coefficient, r); and the amount of IgG needed to obtain OPA (beta coefficient). Non-significant pre-vaccination correlations between OPA and ELISA were found. Vaccination increased the correlation coefficient between OPA and ELISA to a statistically significant level for serotypes 6B, 14 and 23F in samples from haemodialysed patients, for serotypes 14 and 23F in samples from elderly individuals, and for none of the serotypes in samples from transplant recipients. In all cases, except for serotype 23 in transplant recipients, vaccination increased the beta coefficient, indicating that lower amounts of IgG were needed to obtain high OPA titres. A globally lower response was obtained for serotype 23 and/or transplant recipients.

Priorities for antibiotic resistance surveillance in Europe.

Antibiotic resistance is an increasing global problem. Surveillance studies are needed to monitor resistance development, to guide local empirical therapy, and to implement timely and adequate countermeasures. To achieve this, surveillance studies must have standardised methodologies, be longitudinal, and cover a sufficiently large and representative population. However, many fall short of these requirements that define good surveillance studies. Moreover, current efforts are dispersed among many, mostly small, initiatives with different objectives. These studies must be tailored to the various reservoirs of antibiotic-resistant bacteria, such as hospitalised patients, nursing homes, the community, animals and food. Two studies that could serve as examples of tailored programmes are the European Antimicrobial Resistance Surveillance System (EARSS), which collects resistance data during the diagnosis of hospitalised patients, and the DANMAP programme, which collects data in the veterinary sector. As already noted by the WHO, genetic studies that include both the typing of isolates and the characterisation of resistance determinants are necessary to understand fully the spread and development of antibiotic resistance.

Food Safety Hazards and Microbiological Zoonoses in European Meat Imports Detected in Border Inspection in the Period 2008-2013.

Microbiological contaminations and other food safety hazards are omnipresent within the European Union (EU) and a considerable risk for consumers, particularly in imported meat and meat products. The number of rejections at external EU borders has been increasing in recent years. Official authorities in each member state are therefore obliged to notify border rejections of food and animal feed due to a direct or indirect risk to human or animal health. This study explored the trends and temporal and spatial distribution of notifications on food safety hazards between January 2008 and December 2013 with a special emphasis on microbiological zoonoses in meat and meat products including poultry at border checks resulting from the rapid alert system for food and feed (RASFF). Results indicated that border rejection notifications are increasing exponentially, frequently due to Salmonella in poultry and shiga-toxin-producing E. coli in meat and meat products.

Isolation of the membranes of an enterotoxigenic strain of Escherichia coli and distribution of enterotoxin activity in different subcellular fractions.

The intracellular localization of enterotoxin in Escherichia coli AP1, a strain of porcine origin which produces high levels of heat-labile, but no heat-stable enterotoxin, has been examined. The cytoplasmic and outer membranes of this strain both contained enterotoxin activity, while the membranes isolated from a serologically related non-enterotoxigenic strain (E. coli AP2) also of porcine origin, did not show enterotoxin activity. The periplasmic fraction isolated from the enterotoxigenic strain contained considerable enterotoxin activity, but this activity was associated with outer membrane fragments present in the periplasmic fraction. Thus, of the total cellular enterotoxin activity, about 55%, 15% and 30% were present in the outer membrane, cytoplasmic membrane and the cell cytoplasm, respectively. The specific activity of enterotoxin was 20 units per mg protein in the cytoplasm and 90 and 150 units per mg protein in the cytoplasmic and outer membranes, respectively.