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According to existing historiography the coffee house played an important role in the sociabilization of the late seventeenth- and the eighteenth-century bourgeoisie. The assumption in existing historiography is that the bourgeois went to the Dutch coffee houses to socialize, converse about political and ethical issues, and thus achieve personal growth. Sociabilization in the coffeehouses was encouraged by ‘literary socialization’: the conversations were spurred by the bourgeois’ reading of texts and introduced them to literary reading of these texts. In this article, we question this historiography for the case of Amsterdam between 1685 and 1785 by a closer investigation of both literary representations of coffee houses and judicial (notary) sources. Coffee houses often appear as scenes of gambling and violent encounters in the notary archives. Literary representations (plays, diaries) confirm a more dissolute and less civilizing character of the Amsterdam coffee house. Moreover, the number of coffee houses in Amsterdam diminished in the eighteenth century, and literary representations are almost completely absent after 1730. They do not appear in a typical bourgeois novel such as Sara Burgerhart. We conclude that coffee houses did not play the key role in literary socialization and sociabilization previously assumed.

Plastics show the strongest production growth of all bulk materials and are already responsible for 4.5% of global greenhouse gas emissions 1,2. If no new policies are implemented, we project a doubling of global plastic demand by 2050 and more than a tripling by 2100, with an almost equivalent increase in CO 2 emissions. Here we analyse three alternative CO 2 emission-mitigation pathways for the global plastics sector until 2100, covering the entire life cycle from production to waste management. Our results show that, through bio-based carbon sequestration in plastic products, a combination of biomass use and landfilling can achieve negative emissions in the long term; however, this involves continued reliance on primary feedstock. A circular economy approach without an additional bioeconomy push reduces resource consumption by 30% and achieves 10% greater emission reductions before 2050 while reducing the potential of negative emissions in the long term. A circular bioeconomy approach combining recycling with higher biomass use could ultimately turn the sector into a net carbon sink, while at the same time phasing out landfilling and reducing resource consumption. Our work improves the representation of material flows and the circular economy in global energy and emission models, and provides insight into long-term dynamics in the plastics sector.

Contains fulltext : 287797.pdf (Publisher’s version ) (Closed access) Sensory driven activity during early life is critical for setting up the proper connectivity of the sensory cortices. We ask here whether social play behavior, a particular form of social interaction that is highly abundant during postweaning development, is equally important for setting up connections in the developing prefrontal cortex (PFC). Young male rats were deprived from social play with peers during the period in life when social play behavior normally peaks [postnatal day 21-42] (SPD rats), followed by resocialization until adulthood. We recorded synaptic currents in layer 5 cells in slices from medial PFC of adult SPD and control rats and observed that inhibitory synaptic currents were reduced in SPD slices, while excitatory synaptic currents were unaffected. This was associated with a decrease in perisomatic inhibitory synapses from parvalbumin-positive GABAergic cells. In parallel experiments, adult SPD rats achieved more reversals in a probabilistic reversal learning (PRL) task, which depends on the integrity of the PFC, by using a more simplified cognitive strategy than controls. Interestingly, we observed that one daily hour of play during SPD partially rescued the behavioral performance in the PRL, but did not prevent the decrease in PFC inhibitory synaptic inputs. Our data demonstrate the importance of unrestricted social play for the development of inhibitory synapses in the PFC and cognitive skills in adulthood and show that specific synaptic alterations in the PFC can result in a complex behavioral outcome.SIGNIFICANCE STATEMENT This study addressed the question whether social play behavior in juvenile rats contributes to functional development of the prefrontal cortex (PFC). We found that rats that had been deprived from juvenile social play (social play deprivation - SPD) showed a reduction in inhibitory synapses in the PFC and a simplified strategy to solve a complex behavioral task in adulthood. Providing one daily hour of play during SPD partially rescued the cognitive skills in these rats, but did not prevent the reduction in PFC inhibitory synapses. Our results demonstrate a key role for unrestricted juvenile social play in PFC development and emphasize the complex relation between PFC circuit connectivity and cognitive function.

Brain-related comorbidities are frequently observed in chronic obstructive pulmonary disease (COPD) and are related to increased disease progression and mortality. To date, it is unclear which mechanisms are involved in the development of brain-related problems in COPD. In this study, a cigarette smoke and lipopolysaccharide (LPS) exposure murine model was used to induce COPD-like features and assess the impact on brain and behavior. Mice were daily exposed to cigarette smoke for 72 days, except for days 42, 52, and 62, on which mice were intratracheally exposed to the bacterial trigger LPS. Emphysema and pulmonary inflammation as well as behavior and brain pathology were assessed. Cigarette smoke-exposed mice showed increased alveolar enlargement and numbers of macrophages and neutrophils in bronchoalveolar lavage. Cigarette smoke exposure resulted in lower body weight, which was accompanied by lower serum leptin levels, more time spent in the inner zone of the open field, and decreased claudin-5 and occludin protein expression levels in brain microvessels. Combined cigarette smoke and LPS exposure resulted in increased locomotion and elevated microglial activation in the hippocampus of the brain. These novel findings show that systemic inflammation observed after combined cigarette smoke and LPS exposure in this COPD model is associated with increased exploratory behavior. Findings suggest that neuroinflammation is present in the brain area involved in cognitive functioning and that blood-brain barrier integrity is compromised. These findings can contribute to our knowledge about possible processes involved in brain-related comorbidities in COPD, which is valuable for optimizing and developing therapy strategies.

Objective: A fixed 6 mg dexamethasone dose for 10 days is the standard treatment for all hospitalised COVID-19 patients who require supplemental oxygen. Yet, the pharmacokinetic properties of dexamethasone can lead to diminishing systemic dexamethasone exposure with increasing body mass index (BMI). The present study examines whether this translates to overweight and obesity being associated with worse clinical outcomes, defined as ICU admission or in hospital death, in COVID-19 patients treated with fixed-dose dexamethasone. Methods: We conducted a single centre retrospective cohort study in COVID-19 patients who were admitted to a non-ICU ward and were treated with dexamethasone (6 mg once daily for a maximum of ten days) between June 2020 and January 2021. Univariable and multivariable logistic regression analyses were conducted to assess the association between BMI-categories and an unfavourable clinical course (ICU admission and/or in hospital death). Analyses were adjusted for age, comorbidities, inflammatory status, and oxygen requirement at admission. For reference, similar analyses were repeated in a cohort of patients hospitalised before dexamethasone was introduced (March 2020 through May 2020). Results: In patients treated with dexamethasone (n = 385) an unfavourable clinical course was most prevalent in patients with normal weight (BMI < 25) compared to patients with overweight (BMI 25–30) and patients with obesity (BMI ≥ 30) with percentages of 33, 26 and 21% respectively. In multivariable analyses, there was no association between BMI-category and an unfavourable clinical course (respectively with aORs of 0.81 (0.43–1.53) and 0.61 (0.30–1.27) with normal weight as reference). In the reference cohort (n = 249) the opposite was observed with an unfavourable clinical course being most prevalent in patients with overweight (39% vs 28%; aOR 2.17 (0.99–4.76)). In both cohorts, CRP level at admission was higher and lymphocyte count was lower in patients with normal weight compared to patients with obesity. Conclusions: Overweight and obesity are not associated with an unfavourable clinical course in COVID-19 patients admitted to a non-ICU ward and treated with 6 mg dexamethasone once daily.

Our study focuses on myths about older people’s smartphone use. Self-reported data, from Eurostat for example, report access rather than actual usage and are of limited use. What respondents report does not necessarily correspond with their actual smartphone usage behaviour in everyday life. We therefore conducted a tracking study to gain insight into smartphone usage among older adults. Smartphone activity logs were collected from individuals aged 60–79 (N = 303) throughout a period of 28 days between February and May 2019 in Canada, the Netherlands, Spain and Sweden. The data thus obtained on actual smartphone use were critically examined in the light of seven myths related to the smart phone usage of older people in everyday life. We also analysed the data in the context of empirical studies in the field of older people’s digital behaviour. Finally, after drawing our conclusions, we present limitations and sketch implications for future research.

De stelling in deze aflevering van TvCR luidt: ‘In de zaak Gündoğan/Volt wreekte zich het ontbreken van een fatsoenlijke wettelijke regeling over het functioneren van Kamerfracties.’ Max Vetzo pleit tegen deze stelling. Volgens hem schuilt het probleem niet in het ontbreken van objectieve wettelijke normen, maar in institutionele onduidelijkheid over de vraag welke rol de rechter in geschillen over het fractielidmaatschap van Kamerleden toekomt.

Motivation lies at the core of human behavior. It explains why we do what we do. In this article, we seek an explanation for the influence of leadership, purpose, and values on employee engagement through motivation. Engaged employees derive energy from their work, are dedicated, show higher psychological well-being, and perform better. We suspected that motivation, as defined in self-determination theory, is an underlying mechanism that could explain the relationship between leadership and positive outcomes. To this end, we con-ducted five empirical studies in which the fulfillment of the basic psychological needs for autonomy, competence, and connectedness played a central role. We found that engaging leadership, a higher corporate purpose, and intrinsic values stimulated motivation and engagement. The fulfilment of psychological needs (notably autonomy) played an important role in these relationships. A sixth study tested leadership and inspiration in an intervention study. The intervention led to higher motivation among participants, lower absenteeism among employees, and better business performance. Navigating motivation at work supports employees to flourish, develop, and find significance.

AIM: The objective of this study was to describe the use of COVID-19-related medicines during pregnancy and their evolution between the early/late periods of the pandemic. METHODS: Pregnant women who tested positive for SARS-CoV-2 from March 2020 to July 2021 were included using the COVI-PREG registry. Exposure to the following COVID-19-related medicines was recorded: antibiotics, antivirals, hydroxychloroquine, corticosteroids, anti-interleukin-6 and immunoglobulins. We described the prevalence of medicines used, by trimester of pregnancy, maternal COVID-19 severity level and early/late period of the pandemic (before and after 1 July 2020). FINDINGS: We included 1964 pregnant patients who tested positive for SARS-CoV-2. Overall, 10.4% (205/1964) received at least one COVID-19-related medicine including antibiotics (8.6%; 169/1694), corticosteroids (3.2%; 62/1964), antivirals (2.0%; 39/1964), hydroxychloroquine (1.4%; 27/1964) and anti-interleukin-6 (0.3%; 5/1964). The use of at least one COVID-19-related medicine was 3.1% (12/381) in asymptomatic individuals, 4.2% (52/1233) in outpatients, 19.7% (46/233) in inpatients without oxygen, 72.1% (44/61) in those requiring standard oxygen, 95.7% (22/23) in those requiring high flow oxygen, 96.2% (25/26) in patients who required intubation and 57.1% (4/7) among patients who died. The proportion who received medicines to treat COVID-19 was higher before than after July 2020 (16.7% vs. 7.7%). Antibiotics, antivirals and hydroxychloroquine had lower rates of use during the late period. CONCLUSION: Medicine use in pregnancy increased with disease severity. The trend towards increased use of corticosteroids seems to be aligned with changing guidelines. Evidence is still needed regarding the effectiveness and safety of COVID-19-related medicines in pregnancy.

The aim of this work was to evaluate the seasonal effect on the metabolomic profile of the ovarian follicle in Italian Mediterranean buffalo to unravel the causes of the reduced competence during the non-breeding season (NBS). Samples of follicular fluid, follicular cells, cumulus cells and oocytes were collected from abattoir-derived ovaries during breeding season (BS) and NBS and analyzed by 1H Nuclear Magnetic Resonance. The Orthogonal Projections to Latent Structures of the Discriminant Analysis showed clear separation into seasonal classes and Variable Importance in Projection method identified differentially abundant metabolites between seasons. Seasonal differences were recorded in metabolite content in all analyzed components suggesting that the decreased oocyte competence during NBS may be linked to alteration of several metabolic pathways. The pathway enrichment analysis revealed that differences in the metabolites between the seasons were linked to glutathione, energy generating and amino acid metabolism and phospholipid biosynthesis. The current work allows the identification of potential positive competence markers in the follicular fluid as glutathione, glutamate, lactate and choline, and negative markers like leucine, isoleucine and β-hydroxybutyrate. These results form a major basis to develop potential strategies to optimize the follicular environment and the IVM medium to improve the competence of oocytes during the NBS.

Epidemiological studies indicate that chronic obstructive pulmonary disease (COPD) is associated with the incidence of changes in intestinal health. Cigarette smoking, as one of the major causes of COPD, can have an impact on the gastrointestinal system and promotes intestinal diseases. This points to the existence of gut-lung interactions, but an overview of the underlying mechanisms of the bidirectional connection between the lungs and the gut in COPD is lacking. The interaction between the lungs and the gut can occur through circulating inflammatory cells and mediators. Moreover, gut microbiota dysbiosis, observed in both COPD and intestinal disorders, can lead to a disturbed mucosal environment, including the intestinal barrier and immune system, and hence may negatively affect both the gut and the lungs. Furthermore, systemic hypoxia and oxidative stress that occur in COPD may also be involved in intestinal dysfunction and play a role in the gut-lung axis. In this review, we summarize data from clinical research, animal models, and in vitro studies that may explain the possible mechanisms of gut-lung interactions associated with COPD. Interesting observations on the possibility of promising future add-on therapies for intestinal dysfunction in patients with COPD are highlighted.

Epidemiological studies indicate that chronic obstructive pulmonary disease (COPD) is associated with the incidence of changes in intestinal health. Cigarette smoking, as one of the major causes of COPD, can have an impact on the gastrointestinal system and promotes intestinal diseases. This points to the existence of gut-lung interactions, however, an overview of the underlying mechanisms of the bidirectional connection between the lungs and the gut in COPD is lacking. The interaction between the lungs and the gut can occur through circulating inflammatory cells and mediators. Moreover, gut microbiota dysbiosis, observed in both COPD and intestinal disorders, can lead to a disturbed mucosal environment, including the intestinal barrier and immune system, and hence, may negatively affect both the gut and the lungs. Furthermore, systemic hypoxia and oxidative stress that occurs in COPD may also be involved in intestinal dysfunction and play a role in the gut-lung axis. This review summarizes data from clinical research, animal models and in vitro studies that may explain the possible mechanisms of gut-lung interactions associated with COPD. Interesting observations on the possibility of promising future add-on therapies for intestinal dysfunction in COPD patients will be highlighted.

Sustainable ecosystem management relies on our ability to predict changes in plant diversity and to understand the underlying mechanisms. Empirical evidence demonstrates that abundance- and functional-based processes simultaneously explain the loss of plant diversity in response to human activities. Recently, a novel indicator based on percent cover (CoverD) and maximum height (HeightD) of the dominant plant species – space resource utilization (SRUD) – has proven to give robust and better predictions of plant diversity dynamics than community biomass. Whether the superior predictive ability of SRUD is due to its capacity to simultaneously capture abundance- and functional-based processes remains unknown. Here, we tested this hypothesis by quantifying mechanistic links between changes in SRUD and biodiversity in response to nutrients and herbivores. Furthermore, we assessed the relative contribution of dominant, intermediate and rare species to reduced density of individuals by combining null model analysis with field experiments. We found that SRUD successfully captured changes in ground-level light availability and changes in the number of individuals to predict plant diversity dynamics, and each of CoverD and HeightD partly and independently contributed to both processes. Comparative results from null model analysis and field experiments confirmed that individual losses of dominant, intermediate and rare species followed non-random processes. Specifically, compared with random loss process, rare species lost proportionally more individuals and thus disproportionately contributed to species loss, while dominant and intermediate species lost less. Our results demonstrate that SRUD captures both abundance- and functional-based processes thus explaining why SRUD provides more accurate predictions of changes in species diversity. Given that rare species can play an important role in shaping community structure, resisting against invasion, impacting higher trophic levels and providing multiple ecosystem functions, reducing the SRU of dominant species could alleviate the risk of exclusion of rare species by mitigating abundance- and functional-based competition processes.

How we can accelerate the diffusion of new clean energy technologies worldwide is a highly relevant topic for energy and climate policies, as well as industrial policies. We trace the time lag between the introduction and the diffusion of breakthroughs in solar photovoltaic technology and wind power technology. Our results show that both domestic knowledge base and organizational proximity to the country introducing breakthroughs, help latecomer countries catch up by actively innovating in these technologies on their own. Moreover, we find that there are more opportunities for latecomer countries with stronger domestic knowledge base to catch up in solar photovoltaic technology than wind power technology. The results of this paper provide systematic evidence of the technology-sensitive catching-up process in the clean energy technological paradigm.

More than 100 countries have communicated or adopted new Nationally Determined Contributions (NDCs) and net-zero target pledges. We investigate the impact on global, national, sectoral, and individual greenhouse gas emissions projections under different scenarios based on the announced NDCs and net-zero pledges using the IMAGE integrated assessment model. Our results show that while the net-zero pledges, if implemented, could be an important step forward, they are still not enough to achieve the Paris Agreement goals of well below 2°C and preferably 1.5°C by the end of the century. Still, our net-zero scenarios project significant all-sector decarbonization, in particular, electricity; however, certain sectors like industry and transport prove hard to completely abate.

In an attempt to explore further the Madelung fluid-like representation of quantum mechanics, we derive the small perturbation equations of the fluid with respect to its basic states. The latter are obtained from the Madelung transform of the Schrödinger equation eigenstates. The fundamental eigenstates of de Broglie monochromatic matter waves are then shown to be mapped into the simple basic states of a fluid with constant density and velocity, where the latter is the de Broglie group velocity. The normal modes with respect to these basic states are derived and found to also satisfy the de Broglie dispersion relation. Despite being dispersive waves, their propagation mechanism is equivalent to that of sound waves in a classical ideal adiabatic gas. We discuss the physical interpretation of these results.

INTRODUCTION: Adherence to anticancer agents is a critical factor in achieving adequate clinical response, and became a major challenge for patients and caregivers since the increased substitution of parenteral cytostatic by oral drugs. One of the factors that influences adherence is how well informed patients are about their therapy. This study assesses the association between patient satisfaction with information about oral anticancer agents and adherence. MATERIALS AND METHODS: This study was conducted among patients (≥18 years) who began oral anticancer therapy. Patients satisfaction with information and adherence were assessed using validated questionnaires. Adherence was also assessed using refill data. Logistic regression was applied to assess the association between overall patient satisfaction with information and both self-reported adherence and adherence based on an MPR value of above 80%. RESULTS: In total, 124 patients were included in the study. The median (IQR) satisfaction with information was 15.0(4) on a scale of 0-17. Eighty-two percent of participants reported adherence, while the refill data demonstrated that 64.5% of patients had an adherence rate of 80% or higher. Overall satisfaction with information was not significantly associated with self-reported adherence (OR adj 0.98 [95% CI 0.85-1.15]) or refill-based adherence (OR adj 1.11 [95% CI 0.99-1.24]). CONCLUSION: The findings indicate no significant relationship between patient satisfaction with information and adherence. The population was highly satisfied with information about the oral anticancer agents, which indicates a high level of satisfaction with usual care. However, the refill data reveals that 35.5% of patients were not adherent.

We generalize the greedy and lazy $\beta$-transformations for a real base $\beta$ to the setting of alternate bases $\boldsymbol{\beta}=(\beta_0,\ldots,\beta_{p-1})$, which were recently introduced by the first and second authors as a particular case of Cantor bases. As in the real base case, these new transformations, denoted $T_\boldsymbol{\beta}$ and $L_\boldsymbol{\beta}$ respectively, can be iterated in order to generate the digits of the greedy and lazy $\boldsymbol{\beta}$-expansions of real numbers. The aim of this paper is to describe the dynamical behaviors of $T_\boldsymbol{\beta}$ and $L_\boldsymbol{\beta}$. We first prove the existence of a unique absolutely continuous (with respect to an extended Lebesgue measure, called the $p$-Lebesgue measure) $T_\boldsymbol{\beta}$-invariant measure. We then show that this unique measure is in fact equivalent to the $p$-Lebesgue measure and that the corresponding dynamical system is ergodic and has entropy $\frac{1}{p}\log(\beta_{p-1}\cdots \beta_0)$. We then express the density of this measure and compute the frequencies of letters in the greedy $\boldsymbol{\beta}$-expansions. We obtain the dynamical properties of $L_\boldsymbol{\beta}$ by showing that the lazy dynamical system is isomorphic to the greedy one. We also provide an isomorphism with a suitable extension of the $\beta$-shift. Finally, we show that the $\boldsymbol{\beta}$-expansions can be seen as $(\beta_{p-1}\cdots \beta_0)$-representations over general digit sets and we compare both frameworks., Comment: 28 pages, 15 figures

Declines in grassland diversity in response to nutrient addition are a general consequence of global change. This decline in species richness may be driven by multiple underlying processes operating at different time-scales. Nutrient addition can reduce diversity by enhancing the rate of local extinction via competitive exclusion, or by reducing the rate of colonization by constraining the pool of species able to colonize under new conditions. Partitioning net change into extinction and colonization rates will better delineate the long-term effect of global change in grasslands. We synthesized changes in richness in response to experimental fertilization with nitrogen, phosphorus and potassium with micronutrients across 30 grasslands. We quantified changes in local richness, colonization, and extinction over 8–10 years of nutrient addition, and compared these rates against control conditions to isolate the effect of nutrient addition from background dynamics. Total richness at steady state in the control plots was the sum of equal, relatively high rates of local colonization and extinction. On aggregate, 30%–35% of initial species were lost and the same proportion of new species were gained at least once over a decade. Absolute turnover increased with site-level richness but was proportionately greater at lower-richness sites relative to starting richness. Loss of total richness with nutrient addition, especially N in combination with P or K, was driven by enhanced rates of extinction with a smaller contribution from reduced colonization. Enhanced extinction and reduced colonization were disproportionately among native species, perennials, and forbs. Reduced colonization plateaued after the first few (

The effects of home visiting programs to reduce child maltreatment are generally limited and warrant improvement. The present study, therefore, examined whether the effectiveness of a home visitation program in the Netherlands can be improved by adding specific intervention components targeting important risk factors for child maltreatment, namely parental stress, parental anger, and PTSD symptoms. Using a single-case experimental design, nine mothers were assessed weekly during 36 weeks of the Dutch home visiting program VoorZorg, comparing baseline, treatment (i.e., phase with added intervention components), and follow-up. Outcome effects were examined using statistical analyses on a group level and combining statistical and visual analyses on a case level for primary outcomes: perceived stress, parental anger, and PTSD symptoms, and secondary outcomes: risk of child maltreatment and parental sense of competence. As a group, mothers showed a reduction of anger in response to the additional components. No group effects were found for other outcomes. At an individual level, three mothers showed only positive effects, four mothers showed no intervention effects, and two mothers showed mixed effects (i.e., positive on some outcomes and negative on other). Consequently, the component targeting parental anger seems promising, because it can easily be implemented, but it is important to prevent any possible detrimental effects. Effects of the component targeting stress depended on the use of relaxation exercises, and therefore this component should be expanded in such a way that it is more feasible for mothers to implement it.

Our planet is rapidly urbanizing. Research has recognized the complexity of city-driven dynamics, but our political realities have yet to catch up. A new narrative of sustainable urban development must become central to global policymaking to help humanity respond to the most pressing social and environmental challenges.

The primary objective of this study was to investigate the beneficial effects of seed priming and foliar spray of potassium silicate on antioxidant activities under different salinity levels, thereby potentially improving wheat growth. Seeds were soaked into solutions containing potassium silicate (K2SiO3, 1.5 mM) for 6 h, while foliar spray with K2SiO3 (4 mM) was applied at the early and the late stages of tillering. Lake Urmia water was used to prepare salinity levels of 0, 3, 5, 8, 10, 12, and 14 dS m −1. For such traits as anthocyanin, catalase, ascorbate peroxidase, guaiacol peroxidase, and superoxide dismutase activity, an initial increase was observed at lower salinity levels; higher salinities subsequently decreased these traits or they remained mostly constant. Salinity also increased phenol, malondialdehyde, hydrogen peroxide, and polyphenol oxidase, but decreased flavonoid, nitrate content, and nitrate reductase activity. Seed priming and foliar spray provided effective approaches to reduce reactive oxygen species (ROS) manifestation in wheat grown under saline conditions. The improved antioxidant defense abilities by seed priming and foliar spray alleviated the oxidative damage of proteins and lipids and improved nitrate content and nitrate reductase activity.

Purpose: Population-based studies on treatment patterns in oncology and corresponding clinical outcomes can help identify strategies towards optimal value for patients. This study was performed to describe the variation in treatment patterns and major oncological outcomes for muscle-invasive or metastatic bladder cancer (MIBC/mBC) patients in the Netherlands. Methods: Patients diagnosed with cT2-4aN0-3M0-1 disease between 2008 and 2016 in seven large teaching hospitals in the Netherlands were included. Baseline characteristics, disease stage, intended and definitive treatment, and oncological outcomes were collected. Patients were categorized based on cTNM-stage: (1) cT2-4aN0M0, (2) cT2-4aN1-3M0 and (3) cT4b and/or M1. Results: The total study population comprised 1853 patients, of which 1303 patients were diagnosed with cT2-4aN0M0 disease. Overall, curative treatment was intended in 81% (range 74–85%, P value = 0.132). Radical cystectomy (RC) and curative radiotherapy (RTx) ranged between hospitals from 42 to 66% and 13 to 27%, respectively (P value < 0.001). For 334 patients staged cT4b and/or M1, frequencies for palliative therapy and best supportive care (no anti-cancer therapy) ranged between hospitals from 20 to 54% and 44 to 71%, respectively (P value < 0.001). There was no association between hospital site and overall survival (OS) in a univariable and multivariable Cox regression for survival analysis (after adjusting for age and cT-stage), for all three cTNM-groups. Neoadjuvant or induction chemotherapy (NAIC) utilization rates before RC ranged from 8 to 38% (P value < 0.001). Conclusions: There is large inter-hospital variation in treatment intent in MIBC/mBC patients. This variation does not seem to translate to differences in overall survival rates. There is an ongoing trend of increased use of RC. Utilisation of NAIC is relatively low considering European guideline recommendations.

Evidence suggests an impact of the COVID-19 pandemic on mental health, particularly among emerging adults. However, theories on altruism born of suffering or adversarial growth suggest that we might also see prosocial behavior as a function of the pandemic, which may protect against mental health challenges. Because cultural values are central in determining prosocial behavior, the current study explored how cultural values were differentially associated with adaptive prosocial behaviors that might protect against mental health challenges. Participants for the current study included 5,682 young people aged 18–25 years from 14 different countries around the world (68% female, 62% college students). Path analyses suggested that there were few differences in patterns as a function of culture, but revealed that horizontal individualism and horizontal and vertical collectivism were indirectly associated with lower levels of depression via prosocial behavior toward family members. Discussion focuses on the importance of coping by strengthening family relationships via prosocial behavior during the pandemic.

Protein aggregates are hallmarks of neurodegenerative diseases. The protein quality control (PQC) system normally prevents proteins from misfolding and accumulation; however, proteins somehow escape this control on disease. Here we review advances in the role of PQC in protein aggregation and neurodegeneration. We focus primarily on the protein Tau, which aggregates in Alzheimer's disease (AD) and other tauopathies. We also examine recent advances in amyloid fibril structures and the process of fibril formation via phase separation, which are shedding new light on the role of PQC in protein aggregation diseases. While specific components of the quality control system appear to be altered in disease, most chaperones and degradation factors are unchanged at the cellular end stage. Advancing the understanding of quality control factors in neurodegeneration, particularly in the early stages of disease, is among the key challenges for neurodegeneration research.

Whether the use of industrial wood pellets for bioenergy is part of the problem of climate change or part of the solution to climate change has been heavily debated in the academic and political arena. The uncertainty around this topic is impeded by contradicting scientific assessments of carbon impacts of wood pellet use. Spatially explicit quantification of the potential carbon impacts of increased industrial wood pellet demand, including both indirect market and land-use change effects, is required to understand potential negative impacts on carbon stored in the landscape. Studies that meet these requirements are scarce. This study assesses the impact of increased wood pellet demand on carbon stocks in the landscape in the Southern US spatially explicitly and includes the effects of demand for other wood products and land-use types. The analysis is based on IPCC calculations and highly detailed survey-based biomass data for different forest types. We compare a trend of increased wood pellet demand between 2010 and 2030 with a stable trend in wood pellet demand after 2010, thereby quantifying the impact of increased wood pellet demand on carbon stocks in the landscape. This study shows that modest increases in wood pellets demand (from 0.5 Mt in 2010 to 12.1 Mt in 2030), compared to a scenario without increase in wood pellet demand (stable demand at 0.5 Mt), may result in carbon stock gains of 103-229 Mt in the landscape in the Southern US. These carbon stock increases occur due to a reduction in natural forest loss and an increase in pine plantation area compared to a stable-demand scenario. Projected carbon impacts of changes in wood pellet demand were smaller than carbon effects of trends in the timber market. We introduce a new methodological framework to include both indirect market and land-use change effects into carbon calculations in the landscape.

Nutrients and herbivores are well-known drivers of grassland diversity and stability in local communities. However, whether they interact to impact the stability of aboveground biomass and whether these effects depend on spatial scales remain unknown. It is also unclear whether nutrients and herbivores impact stability via different facets of plant diversity including species richness, evenness, and changes in community composition through time and space. We used a replicated experiment adding nutrients and excluding herbivores for 5 years in 34 global grasslands to explore these questions. We found that both nutrient addition and herbivore exclusion alone reduced stability at the larger spatial scale (aggregated local communities; gamma stability), but through different pathways. Nutrient addition reduced gamma stability primarily by increasing changes in local community composition over time, which was mainly driven by species replacement. Herbivore exclusion reduced gamma stability primarily by decreasing asynchronous dynamics among local communities (spatial asynchrony). Their interaction weakly increased gamma stability by increasing spatial asynchrony. Our findings indicate that disentangling the processes operating at different spatial scales may improve conservation and management aiming at maintaining the ability of ecosystems to reliably provide functions and services for humanity.

In this review, we evaluate the claim that translanguaging in the classroom supports the development of the bilingual lexicon by enhancing cross-linguistic transfer. To address this issue, we integrate findings from psycholinguistics and educational sciences in order to identify how effective pedagogical practices for monolingual children can be extended to pedagogical practices for bilingual children. We show that both monolingual and bilingual children benefit from teaching strategies that strengthen the mental connections between semantically and phonologically related words, and that for bilingual children, these strategies should support both within- and cross-language connections. We argue that by stimulating the use of the home language in the classroom, translanguaging strategies like multilingual label quests and multilingual reading and writing can strengthen cross-language connections and, thereby, facilitate cross-linguistic lexical transfer. For closely related languages, stimulation of the home language has the additional benefit of implicitly facilitating the transfer of cognate vocabulary. Explicit instruction about cognates could further stimulate the development of cognate awareness, but whether it also enhances vocabulary learning is still an open question.

Dams affect the natural flow regime by altering the magnitude, timing and frequency of high and low flows. Many river ecosystems impaired by dams are currently being restored. Restoration success is difficult to quantify and is often assessed by comparing the restored system to an unimpaired static ‘reference’ system. However, restoring a river to past environmental conditions and assessing restoration success by comparing it to a static situation neglects natural system dynamics and non-linear, adaptive system responses. With this modelling study we evaluate long-term changes in river morphology, morphodynamics, riparian vegetation cover and habitat suitability of two fish species and two types of wetland vegetation in a meandering gravel bed river after removal of an upstream dam and complete restoration of the natural flow regime. We assessed the ecological and hydromorphodynamic recovery of systems impaired by two different dam operating regimes and three different time periods the dam was present by comparing these to a dynamic undisturbed situation. Modelling results show that recovery potential depends on how much the system has been changed by the dam and the system state at the start of the restoration, rather than the duration of the pressure. Even if the conditions shortly after restoration are comparable to pre-disturbance conditions, there can still be a time-lag in the system response where the future state of the restored system continues to deviate from the undisturbed situation. When this happens, the system can develop into an alternative dynamic equilibrium where recovery becomes increasingly difficult. These results stress the importance of considering natural variability in restored systems as well as in reference systems, requiring detailed spatio-temporal monitoring to assess restoration effects.

PurposePA scholars argue that two gaps are present in the stress literature: (1) “stress” is too simply treated as deleterious and (2) insufficient efforts are made to capture public servants' stress appraisal, i.e. the degree to which stressors are appraised as hindering or challenging. Overcoming Gap 1, this study aims to study stress as a continuum; from distress to eustress. Overcoming Gap 2, stress appraisal is studied through testing the interaction of PsyCap with the two most common clusters of public servants' job stressors: emotional and psychological stressors.Design/methodology/approachHypotheses are tested through structural equation modeling. A sample is used in this study of 1,853 Dutch public servants.FindingsThe results show that emotional and psychological stressors are high, but public servants often appraise them as challenging or as “part of the job”, with consequently no increased distress or decreased eustress. Moreover, psychological capital helps public servants to appraise some of the negative effects of emotional, but not psychological, stressors as less deleterious.Originality/valueBy approaching stress as a continuum, the authors bring in a more complete picture of public servants' stress in PA literature. Moreover, this research shows that the ambiguous results in the existing stress literature about the consequences of emotional and psychological stressors on distress/eustress can partially be explained by sector differences as well as personality differences (i.e. PsyCap). Finally, this study criticizes the one-sided attention to PsyCap as purely positive. PsyCap is not only unhelpful in coping with psychological stressors, it also drains the challenging properties of psychological stressors for dedication.

While important for many industrial applications, chemical reactions responsible for charging of solids in water are often poorly understood. We theoretically investigate the charging kinetics of solid-liquid interfaces, and find that the time-dependent equilibration of surface charge contains key information not only on the reaction mechanism, but also on the valency of the reacting ions. We construct a non-linear differential equation describing surface charging by combining chemical Langmuir kinetics and electrostatic Poisson-Boltzmann theory. Our results reveal a clear distinction between late-time (near-equilibrium) and short-time (far-from-equilibrium) relaxation rates, the ratio of which contains information on the charge valency and ad- or desorption mechanism of the charging process. Similarly, we find that single-ion reactions can be distinguished from two-ion reactions as the latter show an inflection point during equilibration. Interestingly, such inflection points are characteristic of autocatalytic reactions, and we conclude that the Coulombic ion-surface interaction is an autocatalytic feedback mechanism., Comment: 6 pages, 2 figures, Supplemental Material: 4 pages, 2 figures

Group history provides the experiential building blocks that shape social identity. When contemporary events are perceived as having created (or creating) a discontinuity with that history, collective nostalgia is likely to be elicited. Importantly, collective nostalgia is functional-it consolidates social identity, motivating group members to support a return to the group's "true" state of existence. However, no group is a monolith. Factions within a group may have differing opinions on what aspects of the past best represent core features of the ingroup. Variations in the content of the collective nostalgia can cleavage members' responses. Herein, we review research demonstrating the powerful role collective nostalgia and its contents play in intra- and intergroup relations, especially in the socio-political domain.

Although the destabilizing effects of biodiversity loss on ecosystem functioning at local and larger spatial scales are fairly well understood, the consequences of environmental homogenization have received much less attention. Based on detailed measurements of permanent natural forest plots distributed over a large temperate forest region, we explored the effects of environmental heterogeneity and biodiversity on ecosystem stability at local and larger spatial scales. Our results show that the relationship between environmental heterogeneity and biodiversity, as well as between environmental heterogeneity and stability across scales are mostly nonlinear, and that biodiversity stabilizes ecosystem functioning in these natural forests across scales. The unique contribution of biodiversity to stabilizing ecosystem functioning from local to larger scales is greater than the heterogeneity of climate, soils, topography, vegetation, and land cover. To our knowledge, this study is the first to quantify the effects of environmental heterogeneity on the temporal stability of forest productivity in a large natural forest region. Our results imply that biodiversity contributes to stabilizing forest ecosystems from local to larger spatial scales as much as environmental heterogeneity. Research involving large heterogeneous landscapes is critical to understanding the ecological effects of biodiversity across scales. The results of this study are thus relevant for developing effective conservation and land management strategies.

Our planet is rapidly urbanizing. Research has recognized the complexity of city-driven dynamics, but our political realities have yet to catch up. A new narrative of sustainable urban development must become central to global policymaking to help humanity respond to the most pressing social and environmental challenges.

Objectives Most currently available medication self-management support tools do not meet the needs of patients with limited health literacy. Recently, tools that are better tailored to the needs of patients with limited health literacy have been developed. This study aimed to assess the usability of an animated diabetes information tool by patients with diabetes with limited and adequate health literacy levels. Methods Participants with limited and adequate health literacy levels were selected based on three health literacy questions in a screening interview, and asked to use the tool three times a week, after which individual semistructured interviews were conducted. The interview topics were based on the technology acceptance model (i.e. perceived ease of use, perceived usefulness, and intention to use). Twenty-five patients with diabetes were included in the study. Key findings All participants perceived the tool as easy to use due to a clear overview of topics and only personalized information being provided. Those with limited health literacy indicated that they had learned from the tool and had the intention to continue using it in the future. These participants also expressed the need for the tool to be more actively offered by healthcare professionals, while participants with adequate health literacy expressed the need for more in-depth information. Conclusion The tailored self-management support tool was perceived as usable by all participants. To better serve them, the tool could be further improved by addressing the additional needs of people with limited as well as adequate health literacy.

The scarcity of suitable high-resolution archives, such as ancient natural lakes, that span beyond the Holocene, hinders long-term late Quaternary temperature reconstructions in southern Africa. Here we target two cores from Mfabeni Peatland, one of the few long continuous terrestrial archives in South Africa that reaches into the Pleistocene, to generate a composite temperature record spanning the last ∼43 kyr. The Mfabeni Peatland has previously been proven suitable for temperature and hydrological reconstructions based on pollen and geochemical proxies. Here we use branched glycerol dialkyl glycerol tetraethers (brGDGTs) preserved in the Mfabeni peatland to derive a new quantitative air temperature record for south-east Africa. Our temperature record generally follows global trends in temperature and atmospheric CO2 concentrations, but is decoupled at times. Annual air temperatures during Marine Isotope Stage (MIS) 3 were moderately high (c. 20.5 °C), but dropped by c. 5 °C during the Last Glacial Maximum, reaching a minimum at c.16–15 ka. Asynchronous with local insolation, this cooling may have resulted from reduced sea surface temperatures linked to a northward shift in the Southern Hemisphere westerly winds. Concurrent with the southward retreat of the westerlies, and increasing sea surface temperatures offshore, warming from minimum temperatures (c. 15.0 °C) to average Holocene temperatures (c. 20.0 °C) occurred across the deglaciation. This warming was briefly but prominently interrupted by a millennial-scale cooling event of c. 3 °C at c. 2.4 ka, concurrent with a sudden change in hydrological conditions. The average Holocene temperatures of c. 20.0 °C were similar to those reconstructed for MIS 3, but after the 2.4 ka cooling period, air temperatures in the Mfabeni peat recovered and steadily increased towards the present. In summary, our record demonstrates that land temperature in eastern South Africa is highly sensitive to global drivers as well as nearby sea surface temperatures.

Nederland lijkt nog steeds in de ban van het personeelstekort. Het UWV rapporteert in september 2022 dat de arbeidsmarkt voor alle beroepen krap tot zeer krap is. Hoewel de slechtere economische resultaten over een tijdje wellicht gaan leiden tot een stijging van de werkloosheid, wordt er nog volop ingezet op het verlichten van de krapte. In het basisonderwijs starten experimenten met een voltijdbonus die de deeltijder moet verleiden om meer uren te gaan werken. Deeltijdwerk komt in Nederland immers veel voor. Driekwart van de werkende vrouwen heeft een deeltijdbaan, maar ook een vijfde van de werkende mannen. Men wil dus af van het halve werk door te trekken aan het aanbod van arbeid. Dit lijkt een wat al te gemakzuchtige strategie. De arbeidsmarkt kent immers niet alleen een aanbodkant, maar ook een vraagkant. Bovendien laat een te nauwe blik op deeltijdwerkers een veel belangrijke vraagstuk onbesproken: de grote noodzaak om in te zetten op betere banen.

International audience; Diplomacy is sonorous: diplomats deliver speeches, manage silences, applaud, and laugh; they give toasts, clink glasses, and make noise. They listen to the tone of their interlocutors and modulate the timbre of their own voices. Sound – a vital component of representation, mediation, and negotiation – permeates the record of diplomacy, as media transmits images or recordings of leaders in the act of giving a speech or holding a conversation. And music, or “organized sound,” is a standard feature of diplomatic ceremonial, solemn commemorations, social occasions, and the work of public and cultural diplomacy.

Objectives The animated medication information tool ‘Watchyourmeds’ provides information in an accessible manner through animated videos and therefore appears to be especially suitable for people with limited health literacy. This study aimed to assess the implementation of this animated medication information tool in Dutch community pharmacies, with a special focus on patients with limited health literacy. Methods A cross-sectional survey based on the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework was sent to approximately 75% of the ±1900 community pharmacies in the Netherlands through email newsletters of pharmacy networks. Key findings 140 pharmacists (⁓10%) completed the survey and 125 of them (89%) indicated that they offered the animated medication information tool to their patients. 108 pharmacists indicated that the tool was offered to all patients, not only to patients with limited health literacy. The distribution method was primarily passive (patients were given a leaflet and were not explicitly pointed to or informed about the tool). Two frequently cited motivations for offering the tool were that it complemented other sources of information and that the health insurer provided a financial incentive. The main reasons patients refused to use the tool were that they had no access to or no affinity for the required technology. Conclusions This study demonstrated that the tool is used in community pharmacies and that it is offered to all patients, regardless of their presumed health literacy level. A more active method of offering the tool may be warranted to better reach patients with limited health literacy.

Equitable access to health products is a key condition and an indicator for countries’ progress towards Universal Health Coverage (UHC). Access to healthcare, including essential medicines, is a fundamental human right. Realization of this right involves various combinations of public and private financing and service provision arrangements. The pharmaceutical system is an integral subset of the health system which requires mature regulatory structures and robust supply systems to ensure that health goals are achieved and support country efforts to effectively advance UHC. The landscape of pharmaceutical systems is rapidly changing with increasingly complex technologies, often without clear regulatory approaches or mechanisms to achieve equitable access, especially in low and middle-income countries (L&MICs). Medicines are life-enhancing and lifesaving commodities. For a health system to achieve public health goals, medicines should be available in sufficient quantities and be affordable to the population. Health products must also be safe, quality assured, efficacious and used appropriately to achieve desired health outcomes.

In multi-agent systems, norm enforcement is a mechanism for steering the behavior of individual agents in order to achieve desired system-level objectives. Due to the dynamics of multi-agent systems, however, it is hard to design norms that guarantee the achievement of the objectives in every operating context. Also, these objectives may change over time, thereby making previously defined norms ineffective. In this paper, we investigate the use of system execution data to automatically synthesise and revise conditional prohibitions with deadlines, a type of norms aimed at prohibiting agents from exhibiting certain patterns of behaviors. We propose DDNR (Data-Driven Norm Revision), a data-driven approach to norm revision that synthesises revised norms with respect to a data set of traces describing the behavior of the agents in the system. We evaluate DDNR using a state-of-the-art, off-the-shelf urban traffic simulator. The results show that DDNR synthesises revised norms that are significantly more accurate than the original norms in distinguishing adequate and inadequate behaviors for the achievement of the system-level objectives.

The case law overview of the decisions of Court of Justice of the European Union underlines the role language and national constitutional identity play in the free movement rights of persons. While the Treaties adhere to respect for cultural and linguistic diversity (Art. 165(1) TFEU), at the same time protection of the own language may cause restrictions on free movement rights and on the idea, which stands behind the internal Market and EU citizenship rights. The author will map how these rights interact and interplay on the border of the EU and the national competences and interests. The contribution will focus on the role that language has with regard to the free movement of persons, whether economically active or not. What role does language play in the European free movement and how should cultural diversity and national constitutional identity be balanced with language barriers is the key question of the analysis.

The case law overview of the decisions of Court of Justice of the European Union underlines the role language and national constitutional identity play in the free movement rights of persons. While the Treaties adhere to respect for cultural and linguistic diversity (Art. 165(1) TFEU), at the same time protection of the own language may cause restrictions on free movement rights and on the idea, which stands behind the internal Market and EU citizenship rights. The author will map how these rights interact and interplay on the border of the EU and the national competences and interests. The contribution will focus on the role that language has with regard to the free movement of persons, whether economically active or not. What role does language play in the European free movement and how should cultural diversity and national constitutional identity be balanced with language barriers is the key question of the analysis.