Hematocrit Self-Testing in Patients with Polycythemia Vera and Other Hematological Conditions: Assessing the Accuracy of the StatStrip Xpress® 2 LAC/Hb/Hct Device and User Opinion about the Device in Real-World Clinical Practice.

Maintaining hematocrit (Hct) levels below 45% can reduce morbidity and mortality in patients with polycythemia vera (PV). A device that patients can use to self-monitor Hct levels could enable timely interventions if Hct levels increase above 45%, and could improve quality of life (QoL). This study evaluated the accuracy of the StatStrip Xpress® 2 LAC/Hb/Hct meter (Hb/Hct meter) when used by healthcare professionals (HCPs) or patients in clinical practice. Blood samples from 68 visits for 60 patients with PV or other hematological conditions were collected and analyzed by HCPs using a laboratory hematological analyzer, and by patients (self-test) and HCPs (professional test) using the Hb/Hct meter at two Swiss centers. Accuracy was assessed as the mean difference in readings between two users/methods (mdiff, 90% confidence interval; Spearman correlation [r]). The Hct values were similar between the professional test and analyzer (n = 66 comparisons, mdiff = 0.1% [-0.5 to 0.8]; r = 0.95, p < 0.001), the self-test and professional test (n = 62 comparisons, mdiff = -0.2% [-1.1 to 0.7]; r = 0.93, p < 0.001), and the self-test and analyzer (n = 63 comparisons, mdiff = 0.0% [-0.8 to 0.7]; r = 0.94, p < 0.001). The hemoglobin values across users/methods were also similar. Reporting their opinion on the Hb/Hct meter at visit 1, 100% of the patients found it easy to use, and 97% were willing to use it at home. Of the patients with PV, approximately 71% and 56%, respectively, stated that they would feel safer using a self-testing device, and that it would improve their QoL. These findings demonstrate the potential of the Hb/Hct meter for HCP and patient use in real-world settings

Exploring the possibility space: taking stock of the diverse capabilities and gaps in integrated assessment models

Abstract Integrated assessment models (IAMs) have emerged as key tools for building and assessing long term climate mitigation scenarios. Due to their central role in the recent IPCC assessments, and international climate policy analyses more generally, and the high uncertainties related to future projections, IAMs have been critically assessed by scholars from different fields receiving various critiques ranging from adequacy of their methods to how their results are used and communicated. Although IAMs are conceptually diverse and evolved in very different directions, they tend to be criticised under the umbrella of ‘IAMs’. Here we first briefly summarise the IAM landscape and how models differ from each other. We then proceed to discuss six prominent critiques emerging from the recent literature, reflect and respond to them in the light of IAM diversity and ongoing work and suggest ways forward. The six critiques relate to (a) representation of heterogeneous actors in the models, (b) modelling of technology diffusion and dynamics, (c) representation of capital markets, (d) energy-economy feedbacks, (e) policy scenarios, and (f) interpretation and use of model results.</jats:p

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (&gt;= 65 years; estimated glomerular filtration rate &lt;= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off &lt;= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Construction and characterisation of siaD-deleted mutants of Neisseria meningitidis serogroup B as a meningococcal vaccine

In der vorliegenden Dissertation wurde für die Entwicklung eines Lebendimpfstoffs zum Schutz vor Infektionen durch Neisseria meningitidis Serogruppe B zunächst ein geeigneter Impfstamm aus mehreren Neisserienstämmen der Serogruppe B, ST-32 Komplex, ausgewählt. In diesem sollte anschließend die Sicherheit für den Impfstoff-Empfänger durch die unabhängige Deletion sowohl eines Virulenzgens als auch eines Gens, das die homologe Rekombination der Neisserien bedingt, garantiert werden. Als Virulenzgen wurde siaD deletiert, das für ein essentielles Enzym der Kapselbiosynthese kodiert (Edwards et al., 1994). Dabei wurde eine neue Transformationsmethode eingesetzt (modifiziert nach Gunn und Stein; Gunn und Stein, 1996). Die kapsellose siaD-Deletionsmutante wurde dann genotypisch und phänotypisch anhand verschiedener Adhärenz- und Invasionsassays an humanen Epithel-, Endothel- und Dendritischen Zellen geprüft. Dabei fanden sich Unterschiede im Adhärenz und Invasionsverhalten im Vergleich zu einer anderen siaD-Mutante des gleichen Wildtyps. Diese Unterschiede wurden durch eine im Westernblot nachgewiesene, bei beiden siaD-Mutanten unterschiedliche Opa-Expression begründet, da das Opa-Protein als Protein der äußeren Bakterienmembran Oberflächenproteine von humanen Epithel- und Endothelzellen bindet und so zur Adhärenz an die Zielzellen führt (Virji et al., 1993, 1995). Weiterhin sollte in der siaD-Deletionsmutante das für die homologe Rekombination essentielle recA-Gen deletiert werden (Koomey und Falkow, 1987; Miller und Kokjohn, 1990). Der Nachweis einer recA-Deletion gelang trotz mehrfacher Ansätze mit der neuen Transformationsmethode nicht, da die Deletionsrate von recA wahrscheinlich unter der Sensitivität der hier verwendeten Analysemethoden lag.The selection of a possible live-vaccine candidate for Neisseria meningitidis serogroup B and the attenuation of this wildtype by deletion of a virulence gene and a gene for homologous recombination are being described in this thesis. Firstly several wildtypes of Neisseria meningitidis serogroup B are being screened for their ability to proliferate and adhere to human epithelial cells and a wildtype of the ST-32 complex is being selected as the most fitting live-vaccine candidate. In the next step the virulence gene siaD, encoding the polysialyltransferase (Edwards et al., 1994), is being deleted in this wildtype by a new transformation method (modified after Gunn und Stein; Gunn und Stein, 1996), followed by genotypical and phenotypical screening of the unencapsulated, siaD-deleted mutant. The unencapsulated mutant showed unexpected differences in its ability to interact with human epithelial, endothelial and dendritic cells compared to another unencapsulated, siaD-deleted mutant of the same wildtype. A westernblot proved this to be caused by a different opa-expression, a protein of the outer membrane, which is important for the interaction of Neisseria meningitidis with human cells (Virji et al., 1993, 1995). After deleting siaD several attempts are being done to delete the recA gene, which is important for homologous recombination (Koomey und Falkow, 1987; Miller und Kokjohn, 1990), with the same transformation method, but a deletion of recA is not being proved. This may be caused by the sensitivity of the used analysing methods, which may be too low for the transformation rate of this gene

The Link between Stressors and Mastery Experiences: Promotion and Prevention Focus as Antagonistic Explanatory Mechanisms

Mastery is an important recovery experience that refers to off-job activities that provide challenging experiences and learning opportunities in non-work domains (Sonnentag &amp; Fritz, 2007). Mastery is a central source of self-efficacy and personal growth and has also been negatively related to emotional exhaustion, health complaints or depressive symptoms (Sonnentag &amp; Fritz, 2007). Accordingly, mastery is associated with desirable outcomes, underscoring the importance of identifying its drivers. Building on the challenge-hindrance framework, Bennett et al. (2018) conducted a meta-analysis to assess whether challenge and hindrance stressors experienced at work predicted mastery experience outside of the work context. They found that challenge stressors were not associated with mastery experiences, whereas hindrance stressors were positively associated with mastery experiences. In this weekly diary study, we build on the work of Bennett et al. (2018) and examine the role of situational regulatory focus as a mediator that may explain the relationship between challenge and hindrance stressors and mastery. In addition, we hypothesize that goal attainment is a moderator that may explain why Bennett et al. (2018) did not find a significant relationship between challenge stressors and mastery experiences. In terms of regulatory focus, we distinguish between a promotion focus and a prevention focus. People with a promotion focus are particularly sensitive to the presence and absence of positive outcomes: They pursue desires and aspirations and focus on progress, growth, and achievement. Thus, they seek to improve the status quo. In contrast, prevention-focused individuals are more sensitive to the presence and absence of negative outcomes: They strive to fulfill their duties, obligations, and responsibilities, and they focus on protection and safety. Thus, they seek to maintain or restore a satisfactory status quo and to prevent a worse state. Importantly, regulatory focus can vary between individuals, but it can also be induced temporarily, suggesting that there exists within-person variation (Higgins, 1997, 1998; Higgins &amp; Pinelli, 2020; Scholer &amp; Higgins, 2010). By definition, challenge stressors involve the potential for gain, achievement and personal growth whereas hindrance stressors interfere with goal attainment and do not offer opportunities for personal growth (e.g., LePine et al., 2005). Thus, the presence of challenge stressors can be characterized as a “gain-non-gain situation” that is conducive to a promotion focus. In contrast, the presence of hindrance stressors represents a “non-loss-loss situation” that is likely to elicit a prevention focus (Higgins, 1997; Yang &amp; Zhou, 2021). In a promotion-focused state, people are likely to choose an approach strategy, but in a prevention- focused state, they are more likely to choose an avoidance strategy (Higgins, 1997; Scholer &amp; Higgins, 2010). Mastery is a strategy for building resources, experiencing challenges and learning (Sonnentag &amp; Fritz, 2007), and is particularly associated with positive well-being outcomes (Headrick et al., 2022). It is thus consistent with the idea of an approach-oriented strategy (see e.g., Scholer &amp; Higgins, 2010). However, challenge stressors should only exert their potential to enhance a promotion focus when individuals have learned that investing effort will lead to success that is, goal attainment. In contrast, when challenge stressors are not accompanied by goal attainment, individuals may feel disappointed and less inclined to invest any additional resources, leading to prevention focus. The level of goal attainment may also affect the relationship between hindrance stressors and the regulatory focus: When goal attainment is high, hindrance stressors are less likely to be associated with resource loss. Thus, the need to avoid promotion and experience prevention focus may be less pronounced. The role of goal attainment has also been identified by Kronenwett and Rigotti (2022): The authors showed that job demands (e.g., time pressure) differentially affected employees’ well-being through cognitive appraisals depending on whether levels of goal attainment were high or low. Therefore, we formulate the following hypotheses. They refer to the within- and between-person level

Empowering distance: Detachment as a moderator in the relationship between illegitimate tasks and home crafting

Individuals are motivated to approach pleasure and avoid pain (e.g., Higgins, 1998). Thus, they proactively shape their life domains to align their environment with their own abilities and preferences (e.g., Demerouti et al., 2020; Tims &amp; Bakker, 2010). Specifically, individuals may increase their levels of social or structural resources, seek challenges, or reduce social or structural hindering demands, either at work or at home (e.g., Haun et al., 2023). Indeed, several meta-analyses have shown that job crafting is positively related to beneficial outcomes such as job satisfaction, work engagement, and performance (e.g., Rudolph et al., 2017). Notably, crafting aimed at approaching positive states has been shown to be more effective than crafting aimed at avoiding negative states (e.g., Lichtenthaler &amp; Fischbach, 2019). Thus, researchers have explored individual and contextual characteristics that explain such crafting efforts. In general, provided resources are positively associated with job crafting, whereas demands are associated with job crafting to a lesser extent (e.g., Rudolph et al., 2017). However, little research has examined the extent to which job stressors are associated with home crafting. Given the growing interest in home crafting in research (e.g., Demerouti et al., 2020; Haun et al., 2023; Verelst et al., 2023), broadening our understanding of its antecedents is important. As the link between work and at home experiences has already been thoroughly established (e.g., Bennett et al., 2018; Demerouti et al., 2020), we chose to explore potential antecedents rooted in the work domain, namely illegitimate tasks. These refer to tasks that violate what employees believe they can reasonably be expected to do, either because they are unreasonable (i.e., someone else should be doing them) or unnecessary (i.e., they might not need to be done at all; Semmer et al., 2010). Therefore, they are associated with several negative outcomes, including physiological and psychological strain (Ding &amp; Kuvaas, 2023; Semmer et al., 2019). Considering that many studies have found inconsistent effects for the two facets (Ding &amp; Kuvaas, 2023), we investigate unnecessary and unreasonable tasks separately. Two competing mechanisms may account for the lack of or small effects of job demands on craftsmanship in any domain: On the one hand, employees should be motivated to improve any suboptimal conditions, be at home or work. On the other hand, employees might lack the necessary energetic resources to engage in crafting, which have been depleted by coping with previous job demands (Bakker et al., 2023). Stated differently, employees may see a reason to engage in crafting but are not energized enough to actually craft (Parker et al., 2010). Because we expect such a depletion to reduce engagement in job crafting and also extend to less energy to craft in other domains, we do not expect any main findings for the relationship between illegitimate tasks and home crafting. Similarly, Petrou and Bakker (2016), who explored the link between demands, resources, and leisure crafting, did not find a significant main effect from quantitative job demands to leisure crafting. However, when combined with low job autonomy and high home autonomy, weekly job demands were positively related to leisure crafting during that week. Building on the relevance of boundary conditions, we investigate detachment: When individuals effectively detach from work, i.e., gain mental distance from work and successfully reduce strain (Sonnentag &amp; Fritz, 2007), they should be able to turn their pain into gain: Equipped with sufficient energetic resources and their focus set on the home domain, they can craft an optimal environment for themselves. For example, Hur and Shin (2023) demonstrated that a combined measure of detachment and relaxation during the evening related to higher promotion-oriented job crafting the next day via feelings of recovery in the morning. Thus, we expect illegitimate tasks will only be related to increased home crafting for individuals who also report high levels of detachment. Given that particularly approach-oriented strategies in particular require the investment of resources, and consistent with empirical evidence (Hur &amp; Shin, 2023), we narrow our focus to approach-oriented strategies, specifically increasing challenging demands, increasing structural resources, and increasing social resources. So far, there is little evidence of beneficial outcomes of home crafting. Therefore, we aim to answer the question to what extent the investigated facets of home crafting indeed relate to higher well-being in terms of being recovered in the end of the weekend. We investigate the corresponding conditional indirect effects