Abstract Background During the COVID-19 pandemic, non-COVID-19 related healthcare utilization declined in Germany, resulting in care delay, including delays and cancellations of routine, chronic, and even acute care. The aim of this study was to investigate factors (i.e. regional differences and participant characteristics) associated with care delay during the pandemic in Germany using a cross-sectional survey. Methods In October 2022, a total of 117,466 participants from the German National Cohort (NAKO) study completed an online questionnaire on pandemic-related topics, including care delay during the COVID-19 pandemic. Regional differences and participant characteristics associated with care delay were assessed using (multilevel) logistic regression. Results One third of participants reported having experienced care delay. Care delay did not differ across the 13 federal states or 32 districts in Germany for which sufficient data were available. In the medical practice setting, care delay was nearly equally provider- and patient-related and was reported mostly for routine check-ups. In the hospital setting, care delay was predominantly provider-related and reported for newly occurring conditions. The odds for care delay were higher in females vs. males (odds ratio (OR): 1.30; 95% confidence interval (CI): 1.27–1.34), and in participants with vs. without chronic conditions (e.g. mental disorders, OR: 1.41, 95%CI: 1.36–1.46 or cardiovascular diseases, OR: 1.20 95%CI: 1.16–1.24) and decreased with age (e.g. 70 + vs. 50–59 years, OR: 0.59, 95%CI: 0.57–0.62). Conclusion Care delay during the COVID-19 pandemic depended on participant characteristics including age, sex, and preexisting chronic conditions but not on regional (i.e. state and district-level) differences in Germany.

BACKGROUND:A large proportion of Europeans are exposed to high levels of transportation noise, which can cause physiological and psychological stress, leading to negative health impacts. Few studies have examined the association between transportation noise and self-rated health (SRH), a summary indicator of morbidity. OBJECTIVES:We aimed to assess the associations of SRH with both annual average road traffic noise exposure and nighttime transportation noise annoyance, examine geographic differences, evaluate potential effect modification and interaction by sex, and investigate whether annoyance mediates the relationship between road traffic noise and self-rated health. METHODS:Using NAKO baseline data (n = 174,956), we implemented a cross-sectional study using logistic regression to analyze associations of road traffic noise ≥55 dB(A) Lden and nighttime transportation noise annoyance with poor SRH, adjusting for relevant sociodemographic characteristics and environmental co-exposures, including air pollution and greenness. We examined geographic differences, tested for effect modification and interaction by sex, and used path analysis to assess mediation by annoyance. RESULTS:Road traffic noise ≥55 dB(A) (OR 1.06, 95 % CI 1.01; 1.10), and moderate (OR 1.28, 1.23; 1.32) and strong nighttime transportation noise annoyance (OR 1.73, 1.65; 1.81) were associated with higher odds of poor SRH. Associations were similar for males and females, but varied across study regions. The path analysis revealed that road traffic noise was associated with higher odds of poor SRH indirectly via nighttime transportation noise annoyance (indirect effect). CONCLUSIONS:In our study, nighttime transportation noise annoyance was more strongly and consistently associated with poor SRH than road traffic noise. Reducing both transportation noise and related annoyance could help protect population health.

BACKGROUND:The COVID-19 pandemic and its effects have aroused concern all over the world about its impact on mental health. The German National Cohort (NAKO) lends an opportunity to examine trends in altered mental health among adults in Germany during the pandemic. METHODS:We analyzed data from 79 239 participants in the NAKO study who were surveyed with respect to depressive and anxiety symptoms, stress, and self-perceived health at three points in time: at baseline (2014-2019) and in the early (2020) and late (2022) stages of the pandemic. Changes in mental health over time were analyzed with descriptive statistics, Sankey diagrams, and a post-hoc multinomial logistic regression. RESULTS:We observed an initial improvement in self-perceived health from baseline to 2020, but a deterioration from 2020 to 2022. The mental health of most participants remained the same over time. From baseline to 2022, the percentage of participants reporting depressive symptoms rose from 5.9% to 9.7%; rises were also seen in moderate to severe anxiety symptoms, from 3.9% to 6.2%, and in moderate to severe stress, from 4.1% to 10.2%. Both among young adults and among women, deterioration in self-perceived health was more common than improvement. CONCLUSION:Our findings indicate a rise in mental health symptoms among adults in Germany during the pandemic. These findings underscore the need for continuous monitoring and targeted strategies to improve public mental health.

Abstract Background The COVID-19 pandemic and accompanying social distancing measures might have caused adverse health consequences. We aimed to describe changes in participants’ self-rated health and mental health (depression, anxiety, and stress), and investigate factors associated with them. Methods We collected data from the German National Cohort (NAKO). We first described changes in participants’ self-rated health and mental health from the baseline examination (1 to 6 years earlier) to the early phase of the COVID-19 pandemic. We then applied the multinomial logistic regression model (self-rated health) and the quantile regression model (mental health) to investigate the potential factors associated with the health status and changes. Results After a median of 3.1 [2.1, 4.1] years from baseline to the early pandemic phase (N = 91,809), 39.3% of participants with good health and 69.7% with less good health status at baseline reported better health. However, the percentage of participants with high depression, anxiety, and stress scores (≥ 10) increased from 6.2%, 4.1%, and 4.3% to 8.6%, 5.6%, and 10.1%, respectively. In the multivariable models, we found that being younger, being male, highly educated, being employed, having higher life satisfaction at baseline, being more physically active, drinking heavily, and experiencing improved anxiety symptoms were associated with improved self-rated health. In contrast, smoking and having mental health disorders were all associated with worse self-rated health. Our results showed that being younger, being female, smoking, drinking heavily, and drinking more since baseline were associated with higher depression scores. Having had a coronavirus test was associated with worse self-rated health and more severe anxiety and stress. Conclusions During the early COVID-19 pandemic, many participants experienced improvements in self-rated health but suffered deterioration in mental health and physical activity engagement. Female participants, those who were physically inactive, and those with pre-existing mental disorders were more likely to report poorer health.

BACKGROUND:The co-occurrence of different forms of malnutrition has implications for human capital development, as the physiological effects of both anaemia and obesity have been associated with national economic and productivity indicators. This study aims to estimate the prevalence of the double burden of malnutrition including its component conditions, and to identify sociodemographic factors and inflammatory factors associated with the co-occurrence of overweight/obesity and anaemia among non-pregnant women of reproductive age in Panama. METHODS:Using data derived from the 2019 National Health Survey of Panama, we estimated the prevalence of overweight/obesity without anaemia, anaemia without overweight/obesity and the double burden of malnutrition, defined as the co-occurrence of overweight/obesity and anaemia, among non-pregnant women aged 15-49 years. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using multinomial logistic regression to assess the association between sociodemographic factors and the double burden of malnutrition. RESULTS:The weighted prevalence of double burden of malnutrition was 18.6% (95% CI: 15.9%-21.7%). In multivariate adjusted models, compared with women with neither OW/OB nor anaemia, lower vs. higher education (OR= 2.84; 95% CI: 1.24-6.53), ever-having given birth vs. never (OR= 3.01; 95% CI: 1.11-8.15), higher vs. lower inflammation (OR= 9.39; 95% CI: 4.85-18.19) and age 40-49 vs. younger age (OR= 5.99; 95% CI: 1.80-19.95) were associated with double burden of malnutrition. Low education and inflammation were associated with anaemia without overweight/obesity, while older age, indigenous areas, low education, and inflammation were associated with overweight/obesity. CONCLUSION:Double burden of malnutrition affected almost one in five women of reproductive age in Panama. While living in indigenous area was associated with overweight/obesity without anaemia, low education and inflammation emerged as potential shared factors for the individual and combined forms of the double burden of malnutrition.

Recent studies have suggested a potential association of particulate matter (PM) and noise with diabetes and obesity, but studies examining other environmental exposures and their sex-specific and joint associations remain limited. Therefore, we investigated sex-specific individual and joint associations of annual exposure to multiple environmental factors with diabetes and obesity-related measures using cross-sectional data from the population-based multi-center German National Cohort (NAKO). Outcomes included self-reported diabetes mellitus, body mass index (BMI), obesity (BMI ≥30 kg/m2), and waist circumference. Annual mean residential exposures included air pollutants, air temperature, day-evening-night road traffic noise (Lden) and surrounding greenness (normalized difference vegetation index (NDVI)). We used sex-stratified linear and logistic regression models to assess individual associations and quantile g-computation to assess joint associations. Among 174,955 adult participants (50.4% women), 5.6% reported a diabetes diagnosis and 20.9% were obese. An interquartile range increase in PM2.5 and Lden was consistently associated with diabetes and obesity-related measures (e.g., PM2.5-diabetes for men: odds ratio (OR) [95% confidence interval] = 1.12 [1.02; 1.22]; Lden-BMI for women: 0.22 kg/m2 [0.16; 0.27]). Greenness showed non-linear (inverted U-shaped) with all outcomes. An interquartile range increase in multiple exposures simultaneously was associated with higher odds of diabetes, obesity and higher obesity-related measures (e.g., mixture (PM2.5,Lden, lack of NDVI)-diabetes: OR = 1.20 [1.09; 1.33] for men; mixture (PM2.5,Lden, lack of NDVI)-BMI: 0.33 kg/m2 [0.21; 0.44] for women). While longitudinal studies need to confirm these findings, the study highlights that reducing multiple adverse environmental exposures could be potential targets for the prevention of diabetes and obesity.

Background: The COVID-19 pandemic and its effects have aroused concern all over the world about its impact on mental health. The German National Cohort (NAKO) lends an opportunity to examine trends in altered mental health among adults in Germany during the pandemic. Methods: We analyzed data from 79 239 participants in the NAKO study who were surveyed with respect to depressive and anxiety symptoms, stress, and self-perceived health at three points in time: at baseline (2014-2019) and in the early (2020) and late (2022) stages of the pandemic. Changes in mental health over time were analyzed with descriptive statistics, Sankey diagrams, and a post-hoc multinomial logistic regression. Results: We observed an initial improvement in self-perceived health from baseline to 2020, but a deterioration from 2020 to 2022. The mental health of most participants remained the same over time. From baseline to 2022, the percentage of participants reporting depressive symptoms rose from 5.9% to 9.7%; rises were also seen in moderate to severe anxiety symptoms, from 3.9% to 6.2%, and in moderate to severe stress, from 4.1% to 10.2%. Both among young adults and among women, deterioration in self-perceived health was more common than improvement. Conclusion: Our findings indicate a rise in mental health symptoms among adults in Germany during the pandemic. These findings underscore the need for continuous monitoring and targeted strategies to improve public mental health.

BACKGROUND:Polypharmacy is associated with adverse events, impaired quality of life, and increased mortality, but population-based studies that include both prescribed and over-the-counter (OTC) drugs are scarce. METHODS:We analyzed baseline data from the German National Cohort Study (NAKO), Germany's largest population-based cohort study (recruitment 2014-2019, subjects aged 19-74 at baseline). We determined the prevalence of polypharmacy (defined as the reported regular use of ≥5 prescribed or OTC drugs) and hyperpolypharmacy (≥10 drugs), stratified by sex and age. Determinants of polypharmacy were estimated with logistic regression. RESULTS:Out of 203 765 subjects (mean age 49.8 years, 50.4% female), polypharmacy was present in 6869 women (6.7%, 95% confidence interval [6.5%; 6.8%]) and 8126 men (8.0% [7.9%; 8.2%]), hyperpolypharmacy in 505 women (0.5% [0.45%; 0.54%]) and 722 men (0.7% [0.67%; 0.77%]). Both were more prevalent at older ages. Diabetes mellitus and chronic cardiovascular conditions were strong determinants of polypharmacy, and cardiovascular drugs were the most commonly reported type. CONCLUSION:Polypharmacy was common in the NAKO, particularly in older subjects, men, and people with cardiovascular disease. The appropriateness of drug use could not be assessed in this study. Future studies should examine inappropriate polypharmacy and evaluate risk factors and deprescribing strategies.

A strong increase in the prevalence and deaths of Parkinson’s disease (PD) has been reported over the last three decades. Ageing societies, genetic and environmental factors and access to health care contribute to these increases. Using data of the German National Cohort (NAKO) PD classifications based on self-report, claims data and a brief medication based algorithm to increase validity in the absence of neurologic examinations, were compared and the PD incidence, selected non-motor symptoms, functions and vital status were analysed. The algorithm based PD prevalence among 205.000 participants was 0.13% but it was 2.5-fold higher in claims data. Self-reported PD incidence was 0.13% over a median of 4.8 years follow-up, but cases had a 4-fold higher mortality, worse emotional, motoric and olfactory functions and higher prevalences of diabetes, obesity, depression and anxiety. The algorithm based PD prevalence and the mortality risk was similar to considerable older population studies from Europe.

In humans, uric acid is a product of purine metabolism that impacts the vascular system. In addition to effects on arterial vascular tone, associations between serum uric acid concentrations—even in the physiological range—and arterial hypertension and vascular-mediated end-organ damage due to an impact on vascular stiffness have been postulated. Therefore, we aim to investigate a possible cross-sectional association between serum uric acid concentrations in the physiological range and differences in arterial pulse wave velocity (PWV), an indicator of vascular remodeling, with a focus on possible differences between female and male individuals. We analyzed cross-sectional phenotypic and laboratory parameters, including PWV from 70,649 individuals in the population-based German National Cohort (NAKO) in a sex-specific manner. In parallel, we applied a machine learning approach to identify and quantify factors associated with PWV in a hypothesis-free manner. Our analysis uncovered a positive association between serum uric and PWV which was detected even if only individuals with urate values in the physiological range were included (n = 64,095). This correlation was more pronounced in women than in men. In multivariable linear regression models, we observed an association of uric acid (mmol/l) with PWV (m/s) of β = 1.12 (95

Post COVID-19 condition (PCC) is a substantial burden for patients, society, and the healthcare system. Participants of the German National Cohort (NAKO) were asked in an online survey about their self-perceived health, symptoms related to PCC, and infection status. PCC was defined as reporting symptoms for the time window 4-12 months after infection. Of 110,375 respondents (73% response), 86,833 were included in this analysis. Of these, 44,451 (51%) did not report a SARS-CoV-2 infection (no infection), 26,726 (31%) reported an infection but no symptoms 4-12 months after infection (infection/no PCC), and 15,656 (18%) reported an infection and symptoms (PCC). The median number of current symptoms at the time of the survey was two for the "no infection" and the "infection/no PCC" group, and five for the "PCC" group. Participants with PCC had a substantially higher probability of having worse self-perceived health (OR 1.84, 95% CI [1.75; 1.93] compared to the "no infection" group, adjusting for sex, age, education and chronic diseases with elevated risk for developing PCC. After adjusting for the number of current symptoms related to PCC, this difference disappeared, suggesting that the symptoms collected explain the impairment of self-perceived health in the PCC group.

The German National Cohort (NAKO) is the largest population-based epidemiologic cohort study in Germany and investigates the causes of the most common chronic diseases. Between 2014 and 2019, a total of 1.3 million residents aged 20-69 years from 16 German regions were randomly selected from the general population and invited to participate following a highly standardized recruitment protocol. The overall response was 15.6% and differed considerably across study centers (7.6-30.7%). Females were more likely to participate than males (17.5% vs. 14.1%) and participation increased with age (10.2% in age group " < 29 years" up to 20.7% in age group " > 60 years"). Across all study regions, response was highest in rural areas (22.3%), followed by towns and suburbs (17.2%), and was lowest in cities (14.5%). Compared with the general population in the respective study regions, participants with low and medium education are underrepresented in the NAKO sample, while highly educated participants are overrepresented. Participants with non-German nationality and with a migration background are also underrepresented. Participants living in single households are underrepresented, while participants from larger households (2 or more persons) are overrepresented compared to the general population. Survey weights are made available to researchers along with the study data that account for the sampling design and adjust for differences in the distribution of age, sex, nationality (German vs. non-German), migration status, education, and household size.

Background Using data from the largest German cohort study, we aimed to investigate sex differences in the relationship of socioeconomic position (SEP) with cardiovascular disease (CVD), CVD risk factors, and estimated CVD risk. Methods and Results A total of 204 780 (50.5% women) participants from the baseline examination of the population‐based NAKO (German National Cohort) were included. Logistic, multinomial, and linear regression models were used to estimate sex‐specific odds ratios (ORs) and β coefficients with 95% CIs of CVD, CVD risk factors, and very high‐risk score (Systemic Coronary Risk Estimation‐2) for CVD associated with SEP. Women‐to‐men ratios of ORs (RORs) with 95% CIs were estimated. In women compared with men, low versus high SEP (educational attainment and relative income) was more strongly associated with myocardial infarction, hypertension, obesity, overweight, elevated blood pressure, antihypertensive medication, and current alcohol consumption, but less strongly with current and former smoking. In women with the lowest versus highest educational level, the OR for a very high 10‐year CVD risk was 3.61 (95% CI, 2.88–4.53) compared with 1.72 (95% CI, 1.51–1.96) in men. The women‐to‐men ROR was 2.33 (95% CI, 1.78–3.05). For the comparison of low versus high relative income, the odds of having a very high 10‐year CVD risk was 2.55 (95% CI, 2.04–3.18) in women and 2.25 (95% CI, 2.08–2.42) in men (women‐to‐men ROR, 1.31 [95% CI, 1.05–1.63]). Conclusions In women and men, there was an inverse relationship between indicators of SEP and the likelihood of having several CVD risk factors and a very high 10‐year CVD risk. This association was stronger in women, suggesting that CVD risk is more strongly influenced by SEP in women compared with men.

Background The educational gradient in depressive symptoms is well documented. Gender and history of migration have also been found to be associated with depressive symptoms. Intersectional approaches enable the analysis of the interplay of different social factors at a time to gain a deeper understanding of inequalities in depressive symptoms. In this study, intersectional inequalities in depressive symptoms according to education, gender and history of migration are analysed. Methods The German National Cohort (NAKO, N = 204,783) collected information on depressive symptoms (PHQ-9), which was used as an outcome variable. Educational attainment (ISCED-97), gender, and history of migration constituted the different social strata in the analyses. The predicted probabilities of depressive symptoms for 30 social strata were calculated. Multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) was applied, using logistic regression and social strata were introduced as higher-level unit interaction terms. Results The analyses revealed an educational gradient in depressive symptoms, with differences within each educational group when gender and history of migration were introduced to the models. The predicted probabilities of depressive symptoms varied between the most advantaged and the most disadvantaged social strata by more than 20% points. Among the three studied variables, education contributed the most to the variance explained by the MAIHDA models. The between-strata differences were largely explained by additive effects. Conclusions We observed a robust educational gradient in depressive symptoms, but gender and history of migration had substantial contribution on the magnitude of educational inequalities. An intersectional perspective on inequalities in depressive symptoms enhances current knowledge by showing that different social dimensions may intersect and contribute to inequalities in depressive symptoms. Future studies on inequalities in depression may greatly benefit from an intersectional approach, as it reflects lived inequalities in their diversity.

AIMS:Resettlers from the former Soviet Union are one of the largest migrant groups in Germany. Previous studies found lower cardiovascular disease (CVD) mortality among resettlers compared to Germans without migration background (autochthonous). Other studies have shown a higher prevalence of CVD risk factors among resettlers, suggesting a higher CVD mortality. The German National Cohort (NAKO) provides an opportunity to explore these discrepancies. METHODS:This study used baseline data from NAKO and compared age-adjusted percentages of self-reported CVD and associated risk factors between the two groups. Logistic regression models estimated adjusted odds ratios (OR) for associations between resettler status and outcomes. RESULTS:Among 204,751 participants aged 19-75, 3580 were resettlers and 169,538 autochthonous Germans. Male resettlers had lower odds of risky alcohol consumption (OR: 0.55; 95 %CI: 0.49-0.63) but higher odds of ever smoking (OR: 1.26; 95 %CI: 1.13-1.41) compared to autochthonous German men. Female resettlers showed higher prevalence of hypertension, diabetes mellitus, obesity, and elevated cholesterol/triglycerides, but lower prevalence of risky alcohol consumption and smoking. In men, the odds of peripheral artery disease (PAD) (OR: 0.46; 95 %CI: 0.21-0.97) and any CVD (OR: 0.81; 95 %CI: 0.66-0.98) were lower among resettlers. No other notable differences in clinical CVDs were observed in men. CONCLUSION:Resettlers showed differences regarding CVD risk factor distribution compared to autochthonous Germans. These differences appear to balance out, leading to similar overall CVD prevalence, except for a lower prevalence of PAD and total CVD in male resettlers. Future longitudinal data will allow to explore long-term CVD trajectories. LAY SUMMARY:We compared the prevalence of cardiovascular diseases (CVD) in a special group of migrants (resettlers from the former Soviet Union; German: (Spät-)Aussiedler) and autochthonous Germans, using data from the German National Cohort (NAKO) and investigated risk factors frequencies for these diseases in both groups. We found that male resettlers had less of risky alcohol consumption but smoked more than autochthonous German men. Female resettlers showed higher prevalence of hypertension, diabetes mellitus, obesity, and elevated cholesterol and triglyceride levels, but lower prevalence of risky alcohol consumption and smoking. The prevalence of most CVDs was similar in both groups, except of peripheral artery disease and all CVDs combined which we found less frequent in male resettlers.

Background Intersectionality has contributed to novel insights in epidemiology. However, participants of epidemiological studies have rarely been characterised from an intersectional perspective. We aimed to show the gained insights of an intersectionality-informed approach to describing a study population by comparing it to a conventional approach. Methods We used data of the German National Cohort (NAKO), which recruited 205,415 participants between 2014 and 2019. In the conventional approach, marginal proportions of educational level, cohabitation status, and country of birth were compared between the study populations of the NAKO and the German census survey (MZ) of 2014. In the intersectionality-informed approach, so-called intersectional population strata were constructed by cross-classifying educational level, cohabitation status, and country of birth. Proportions of these strata were also compared between NAKO and MZ. All analyses were stratified by sex and age group. Results The conventional approach showed that the proportion of people with low education was lower in the NAKO compared to the MZ in all sex and age strata. Similarly, proportions of all intersectional population strata with low education were lower in the NAKO. Concerning cohabitation, the conventional approach showed that the proportion of those living without a partner was lower in the NAKO than in the MZ for women under 60 and men. The intersectionality-informed approach revealed that the proportions of some subgroups of those living without a partner were higher in the NAKO than in the MZ. These were intersectional population strata who lived without a partner, had a high level of education and were born in Germany. The intersectionality-informed approach revealed similar within-group heterogeneity for country of birth, showing that not all proportions of foreign-born people were lower in the NAKO compared to the MZ. Proportions of foreign-born with high education who lived with a partner were higher. Conclusions Our results showed that heterogeneity within social categories can be revealed by applying the concept of intersectionality when comparing study participants with an external population. This way, an intersectionality-informed approach contributes to describing social complexity among study participants more precisely. Furthermore, results can be used to reduce participation barriers in a more targeted way.

Background: Childhood trauma is associated with somatic and mental illness in adulthood. The strength of the association varies as a function of age, sex, and type of trauma. Pertinent studies to date have mainly focused on individual diseases. In this study, we investigate the association between childhood trauma and a multiplicity of somatic and mental illnesses in adulthood. Methods: Data from 156 807 NAKO Health Study participants were analyzed by means of logistic regressions, with adjustment for age, sex, years of education, and study site. The Childhood Trauma Screener differentiated between no/minor (n = 115 891) and moderate/severe childhood trauma (n = 40 916). The outcome variables were medical diagnoses of five somatic and two mental health conditions as stated in the clinical history. Results: Persons with childhood trauma were more likely to bear a diagnosis of all of the studied conditions: cancer (odds ratio [OR] = 1.10; 95% confidence interval: [1.05; 1.15]), myocardial infarction (OR = 1.13 [1.03; 1.24]), diabetes (OR = 1.16, [1.10; 1.23]), stroke (OR = 1.35 [1.23; 1.48]), chronic obstructive pulmonary disease (OR = 1.45 [1.38; 1.52]), depression (OR = 2.36 [2.29; 2.43]), and anxiety disorders (OR = 2.08 [2.00; 2.17]). All of these associations were stronger in younger persons, regardless of the nature of childhood trauma. Differences between the sexes were observed only for some of these associations. Conclusion: Childhood trauma was associated with a higher probability of developing mental as well as somatic illness in adulthood. As childhood trauma is an element of individual history that the victim has little to no control over, and because the illnesses that can arise in adulthood in association with it are a heavy burden on the affected persons and on society, there is a need for research on these associations and for the development of preventive measures.

Childhood trauma is associated with somatic and mental illness in adulthood. The strength of the association varies as a function of age, sex, and type of trauma. Pertinent studies to date have mainly focused on individual diseases. In this study, we investigate the association between childhood trauma and a multiplicity of somatic and mental illnesses in adulthood.