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Jil Sander is known for designing well sculptured, high quality clothes in subdued colors. This comprehensive book presents her work from the late 1960s to 2014. Challenging the styles of flamboyant femininity, her collections delighted the fashion world with their purity. She proposed a modernity which did away with senseless ornaments, while dynamizing the individual. This book will showcase the ingenuity and creative power of a designer who aimed at underlining a person's personality. More than 150 illustrations present the Jil Sander vision which had a huge impact not only on fashion, but on product design, advertising campaigns, and store architecture as well. Exhibition: Museum Angewandte Kunst, Frankfurt am Main, Germany (04.11.2017-06.05.2018).

Patients often report various symptoms after recovery from acute COVID-19. Previous studies on post-COVID-19 condition have not corrected for the prevalence and severity of these common symptoms before COVID-19 and in populations without SARS-CoV-2 infection. We aimed to analyse the nature, prevalence, and severity of long-term symptoms related to COVID-19, while correcting for symptoms present before SARS-CoV-2 infection and controlling for the symptom dynamics in the population without infection. This study is based on data collected within Lifelines, a multidisciplinary, prospective, population-based, observational cohort study examining the health and health-related behaviours of people living in the north of the Netherlands. All Lifelines participants aged 18 years or older received invitations to digital COVID-19 questionnaires. Longitudinal dynamics of 23 somatic symptoms surrounding COVID-19 diagnoses (due to SARS-CoV-2 alpha [B.1.1.7] variant or previous variants) were assessed using 24 repeated measurements between March 31, 2020, and Aug 2, 2021. Participants with COVID-19 (a positive SARS-CoV-2 test or a physician's diagnosis of COVID-19) were matched by age, sex, and time to COVID-19-negative controls. We recorded symptom severity before and after COVID-19 in participants with COVID-19 and compared that with matched controls. 76 422 participants (mean age 53·7 years [SD 12·9], 46 329 [60·8%] were female) completed a total of 883 973 questionnaires. Of these, 4231 (5·5%) participants had COVID-19 and were matched to 8462 controls. Persistent symptoms in COVID-19-positive participants at 90–150 days after COVID-19 compared with before COVID-19 and compared with matched controls included chest pain, difficulties with breathing, pain when breathing, painful muscles, ageusia or anosmia, tingling extremities, lump in throat, feeling hot and cold alternately, heavy arms or legs, and general tiredness. In 12·7% of patients, these symptoms could be attributed to COVID-19, as 381 (21·4%) of 1782 COVID-19-positive participants versus 361 (8·7%) of 4130 COVID-19-negative controls had at least one of these core symptoms substantially increased to at least moderate severity at 90–150 days after COVID-19 diagnosis or matched timepoint. To our knowledge, this is the first study to report the nature and prevalence of post-COVID-19 condition, while correcting for individual symptoms present before COVID-19 and the symptom dynamics in the population without SARS-CoV-2 infection during the pandemic. Further research that distinguishes potential mechanisms driving post-COVID-19-related symptomatology is required. ZonMw; Dutch Ministry of Health, Welfare, and Sport; Dutch Ministry of Economic Affairs; University Medical Center Groningen, University of Groningen; Provinces of Drenthe, Friesland, and Groningen.

Protein misfolding and aggregation are typically perceived as inevitable and detrimental processes tied to a stress- or age-associated decline in cellular proteostasis. A careful reassessment of this paradigm in the E. coli model bacterium revealed that the emergence of intracellular protein aggregates (PAs) was not related to cellular aging but closely linked to sublethal proteotoxic stresses such as exposure to heat, peroxide, and the antibiotic streptomycin. After removal of the proteotoxic stress and resumption of cellular proliferation, the polarly deposited PA was subjected to limited disaggregation and therefore became asymmetrically inherited for a large number of generations. Many generations after the original PA-inducing stress, the cells inheriting this ancestral PA displayed a significantly increased heat resistance compared to their isogenic, PA-free siblings. This PA-mediated inheritance of heat resistance could be reproduced with a conditionally expressed, intracellular PA consisting of an inert, aggregation-prone mutant protein, validating the role of PAs in increasing resistance and indicating that the resistance-conferring mechanism does not depend on the origin of the PA. Moreover, PAs were found to confer robustness to other proteotoxic stresses, as imposed by reactive oxygen species or streptomycin exposure, suggesting a broad protective effect. Our findings therefore reveal the potential of intracellular PAs to serve as long-term epigenetically inheritable and functional memory elements, physically referring to a previous cellular insult that occurred many generations ago and meanwhile improving robustness to a subsequent proteotoxic stress. The latter is presumably accomplished through the PA-mediated asymmetric inheritance of protein quality control components leading to their specific enrichment in PA-bearing cells.

Aims/hypothesisType 2 diabetes mellitus is a major health burden disproportionately affecting those with lower educational attainment (EA). We aimed to obtain causal estimates of the association between EA and type 2 diabetes and to quantify mediating effects of known modifiable risk factors.MethodsWe applied two-step, two-sample multivariable Mendelian randomisation (MR) techniques using SNPs as genetic instruments for exposure and mediators, thereby minimising bias due to confounding and reverse causation. We leveraged summary data on genome-wide association studies for EA, proposed mediators (i.e. BMI, blood pressure, smoking, television watching) and type 2 diabetes. The total effect of EA on type 2 diabetes was decomposed into a direct effect and indirect effects through multiple mediators. Additionally, traditional mediation analysis was performed in a subset of the National Health and Nutrition Examination Survey 2013–2014.ResultsEA was inversely associated with type 2 diabetes (OR 0.53 for each 4.2 years of schooling; 95% CI 0.49, 0.56). Individually, the largest contributors were BMI (51.18% mediation; 95% CI 46.39%, 55.98%) and television watching (50.79% mediation; 95% CI 19.42%, 82.15%). Combined, the mediators explained 83.93% (95% CI 70.51%, 96.78%) of the EA–type 2 diabetes association. Traditional analysis yielded smaller effects but showed consistent direction and priority ranking of mediators.Conclusions/interpretationThese results support a potentially causal protective effect of EA against type 2 diabetes, with considerable mediation by a number of modifiable risk factors. Interventions on these factors thus have the potential of substantially reducing the burden of type 2 diabetes attributable to low EA.

Objectives Individual characteristics including poor health are well-known to affect labour market participation. However, less is known on the role of health at the residential neighbourhood level. This study examines cross-sectional and longitudinal associations between neighbourhood health and employment status and the moderating role of individual health in the association between neighbourhood health and employment status. Methods Individual level data from the Lifelines Cohort Study ( n  = 137,921) was matched with full-population neighbourhood health data and registry data from Statistics Netherlands on employment status with up to 14 years of follow-up. Neighbourhood health indicators included the proportion of individuals in poor self-reported health (nHealth) and with a chronic disease (nDisease) within neighbourhoods, divided in tertiles (T1, T2, T3). Individual health included dichotomized measures of self-reported poor health (iHealth) and the presence of a chronic disease (iDisease). Employment status comprised the categories employed, unemployed, work disabled, economically inactive and early retired. Logistic and cause-specific Cox regression analyses, including interaction terms between iHealth and nHealth, were used to examine the associations with employment status. Results Poorest nHealth and nDisease tertiles were associated with higher risks of unemployment and work disability. Cross-sectional odds ratios (OR)s for nHealth T3 were: 2.22 (95% CI: 2.06─2.39) for unemployment and 1.98 (95% CI: 1.81─2.16) for work disability. Longitudinal hazard ratios (HR)s for nHealth T3 were: 1.27 (95% CI: 1.22─1.32) for unemployment and 1.59 (95% CI: 1.45─1.74) for work disability. Associations for nDisease were weaker but statistically significant. iHealth and iDisease moderated the associations but stratified analyses yielded inconclusive results. Conclusions Neighbourhood health promotion may have societal and economic benefits by extending individual’s working lives.

Organisms respond to environmental changes by adapting the expression of key genes. However, such transcriptional reprogramming requires time and energy, and may also leave the organism ill-adapted when the original environment returns. Here, we study the dynamics of transcriptional reprogramming and fitness in the model eukaryote Saccharomyces cerevisiae in response to changing carbon environments. Population and single-cell analyses reveal that some wild yeast strains rapidly and uniformly adapt gene expression and growth to changing carbon sources, whereas other strains respond more slowly, resulting in long periods of slow growth (the so-called \"lag phase\") and large differences between individual cells within the population. We exploit this natural heterogeneity to evolve a set of mutants that demonstrate how the frequency and duration of changes in carbon source can favor different carbon catabolite repression strategies. At one end of this spectrum are \"specialist\" strategies that display high rates of growth in stable environments, with more stringent catabolite repression and slower transcriptional reprogramming. The other mutants display less stringent catabolite repression, resulting in leaky expression of genes that are not required for growth in glucose. This \"generalist\" strategy reduces fitness in glucose, but allows faster transcriptional reprogramming and shorter lag phases when the cells need to shift to alternative carbon sources. Whole-genome sequencing of these mutants reveals that mutations in key regulatory genes such as HXK2 and STD1 adjust the regulation and transcriptional noise of metabolic genes, with some mutations leading to alternative gene regulatory strategies that allow \"stochastic sensing\" of the environment. Together, our study unmasks how variable and stable environments favor distinct strategies of transcriptional reprogramming and growth.

Nurses and nursing aides are at high risk of developing musculoskeletal pain (MSP). This study aimed to evaluate a multifaceted intervention to prevent and manage MSP in two hospitals. We performed a two-armed cluster randomized controlled trial, with a late intervention control group. Clusters were independent hospital units with nursing staff as participants. The intervention comprised three evidence-based components: participatory ergonomics, health promotion activities and case management. Both the intervention and the control group received usual occupational health care. The intervention lasted one year. MSP and work functioning data was collected at baseline, six and 12-month follow-up. Odds ratios (OR) and their 95% confidence intervals (95%CI) were calculated for MSP risk in the intervention group compared to the control group using logistic regression through GEE. Differences in work functioning between the intervention and control group were analyzed using linear regression through GEE. The incidence of sickness absence was calculated through logistic regression and Cox proportional hazard modeling was used to analyze the effect of the intervention on sickness absence duration. Eight clusters were randomized including 473 nurses and nursing aides. At 12 months, the intervention group showed a statistically significant decrease of the risk in neck, shoulders and upper back pain, compared to the control group (OR = 0.37; 95%CI = 0.14-0.96). A reduction of low back pain was also observed, though non statistically significant. We found no differences regarding work functioning and the incidence and duration of sickness absence. The intervention was effective to reduce neck, shoulder and upper back pain. Our results, though modest, suggests that interventions to prevent and manage MSP need a multifactorial approach including the three levels of prevention, and framed within the biopsychosocial model.

Background Evidence on the association between the presence of fast-food outlets and Body Mass Index (BMI) is inconsistent. Furthermore, mechanisms underlying the fast-food outlet presence-BMI association are understudied. We investigated the association between the number of fast-food outlets being present and objectively measured BMI. Moreover, we investigated to what extent this association was moderated by neighbourhood socio-economic status (NSES) and healthy food outlets. Additionally, we investigated mediation by frequency of fast-food consumption and amount of fat intake. Methods In this cross-sectional study, we used baseline data of adults in Lifelines ( N  =  149,617 ). Geo-coded residential addresses were linked to fast-food and healthy food outlet locations. We computed the number of fast-food and healthy food outlets within 1 kilometre (km) of participants’ residential addresses (each categorised into null, one, or at least two). Participants underwent objective BMI measurements. We linked data to Statistics Netherlands to compute NSES. Frequency of fast-food consumption and amount of fat intake were measured through questionnaires in Lifelines. Multivariable multilevel linear regression analyses were performed to investigate associations between fast-food outlet presence and BMI, adjusting for individual and environmental potential confounders. When exposure-moderator interactions had p -value < 0.10 or improved model fit (∆AIC ≥ 2), we conducted stratified analyses. We used causal mediation methods to assess mediation. Results Participants with one fast-food outlet within 1 km had a higher BMI than participants with no fast-food outlet within 1 km (B = 0.11, 95% CI: 0.01, 0.21). Effect sizes for at least two fast-food outlets were larger in low NSES areas (B = 0.29, 95% CI: 0.01, 0.57), and especially in low NSES areas where at least two healthy food outlets within 1 km were available (B = 0.75, 95% CI: 0.19, 1.31). Amount of fat intake, but not frequency of fast-food consumption, explained this association for 3.1%. Conclusions Participants living in low SES neighbourhoods with at least two fast-food outlets within 1 km of their residential address had a higher BMI than their peers with no fast-food outlets within 1 km. Among these participants, healthy food outlets did not buffer the potentially unhealthy impact of fast-food outlets. Amount of fat intake partly explained this association. This study highlights neighbourhood socio-economic inequalities regarding fast-food outlets and BMI.

Jobs characterized by low job demands and high job resources are associated with better work outcomes, yet it remains unclear whether this is the case for workers with depression. This study examined whether depression moderates the relationship between job demands, job resources, and maintaining employment. Data from the longitudinal population-based Lifelines cohort study were matched with register data on employment from Statistics Netherlands (N=55 950). Job demands included quantitative demands and work pace; job resources included influence at work and possibilities for development. The two-way interaction between job demands and depression and the three-way interaction between job demands, job resources and depression were examined in a zero-inflated Poisson regression model with path 1, including a binary employment outcome, and path 2, a count variable including months out of employment. The interaction effect of job demands and depression on being employed was significant [b=-0.22, 95% confidence interval (CI) -0.44‒0.01]. Workers without depression were more likely to be employed whereas workers with depression were less likely to be employed if they had high job demands. The three-way interaction between job demands, job resources, and depression was significant for months out of employment (b=0.15, 95% CI 0.01‒0.29), indicating that workers with depression had more months out of employment when reporting high job demands and high job resources compared to workers without depression. Discussion Although increasing influence at work and possibilities for development to prevent negative work outcomes may be beneficial for workers without depression, this approach might be limited for workers with depression.

Background Young adults in Neither in Employment, Education nor Training (NEET) are at risk of adverse labour market outcomes. Earlier studies often measured NEET status at one time point or compared persistent NEETs with non-NEETs, neglecting other patterns of NEET status. Evidence on early life factors associated with NEET patterns is lacking. This study aims to (i) identify patterns of NEET status over time and (ii) examine whether factors in childhood and adolescence are associated with these patterns. Methods Data were used from 1499 participants of the TRacking Adolescents’ Individual Lives Survey (TRAILS), a Dutch prospective cohort study with 15-year follow-up. NEET status was assessed at ages 19, 22 and 26. Socioeconomic status of parents (SES), intelligence and negative life events were measured at age 11, educational attainment at age 26 and mental health problems at ages 11, 13.5 and 16. Data were analyzed using multinomial logistic regression analysis. Results Four NEET patterns were identified: (i) non-NEETs (85.2%), (ii) early NEETs (4.5%), (iii) late NEETs (5.7%) and (iv) persistent NEETs (4.5%). Reporting internalizing problems at age 11 was a risk factor for early and late NEETs [odds ratio (OR) 2.77, 95% confidence interval (CI) 1.16–6.62; OR 5.00, 95% CI 2.22–11.3, respectively]. Low parental SES, lower intelligence scores and negative life events (≥3) were risk factors for persistent NEETs (OR 4.45, 95% CI 2.00–9.91; OR 0.96, 95% CI 0.94–0.98; OR 4.42, 95% CI 1.62–12.08, respectively). Conclusions The results highlight the importance of timing and duration of NEET status and emphasize the need for tailored interventions to prevent specific NEET patterns.