Renal function-adapted D-dimer cutoffs in combination with a clinical prediction rule to exclude pulmonary embolism in patients presenting to the emergency department.

D-dimer levels significantly increase with declining renal function and hence, renal function-adjusted D-dimer cutoffs to rule out pulmonary embolism were suggested. Aim of this study was to "post hoc" validate previously defined renal function-adjusted D-dimer levels to safely rule out pulmonary embolism in patients presenting to the emergency department. In this retrospective, observational analysis, all patients with low to intermediate pre-test probability receiving D-dimer measurement and computed tomography angiography (CTA) to rule out pulmonary embolism between January 2017 and December 2020 were included. Previously defined renal function-adjusted D-dimer cutoffs (1306 µg/l for moderate and 1663 µg/l for severe renal function impairment) were applied to determine sensitivity, specificity, negative and positive predictive values. One thousand, three hundred sixty-nine patients were included of which 229 (17%) were diagnosed with pulmonary embolism. The estimated glomerular filtration rate (eGFR) was ≥ 60 ml/min in 1079 (79%), 30-59 ml/min in 266 (19%) and < 30 ml/min in 24 (2%) patients. Only three patients (1.1%) with an eGFR < 60 ml/min had a D-dimer level < 500 µg/l. There was a significant correlation between D-dimer and eGFR (R = - 0.159, p < 0.001). Calculated on the standard D-dimer cutoff value of 500 µg/l, sensitivity of D-dimer testing was 97% for patients with an eGFR ≥ 60 ml/min and 100% for those with 30-60 ml/min, while specificity decreased in patients with renal function impairment. A negative predictive value of 0.99 as a premise to safely rule out pulmonary embolism was achieved by applying a D-dimer cutoff of 1480 µg/l for eGFR 30-59 ml/min and 1351 µg/l for eGFR < 30 ml/min. The findings of this study underline that application of renal function-adapted D-dimer levels in combination with a clinical prediction rule appears feasible to rule out pulmonary embolism. Out of the current dataset, renal function-adjusted D-dimer cutoffs to rule out pulmonary embolism were slightly different compared to previously defined cutoffs. Further studies on a larger scale are needed to validate possible renal function-adjusted D-dimer cutoffs

Prevalence and factors associated with chronic use of levothyroxine: A cohort study

Importance Levothyroxine prescriptions are rising worldwide. However, there are few data on factors associated with chronic use. Objective To assess the prevalence of chronic levothyroxine use, its rank among other chronic drugs and factors associated with chronic use. To assess the proportion of users outside the therapeutic range of thyroid-stimulating hormone (TSH). Design Cohort study (CoLaus|PsyCoLaus) with recruitment from 2003 to 2006. Follow-ups occurred 5 and 10 years after baseline. Participants A random sample of Lausanne (Switzerland) inhabitants aged 35-75 years. Main outcomes We evaluated the prevalence of chronic levothyroxine use and we then ranked it among the other most used chronic drugs. The ranking was compared to data from health insurance across the country. We assessed the association between each factor and chronic levothyroxine use in multivariable logistic regression models. The proportion of chronic levothyroxine users outside the usual TSH therapeutic range was assessed. Results 4,334 participants were included in the analysis (mean±SD age 62.8±10.4 years, 54.9% women). 166 (3.8%) participants were chronic levothyroxine users. Levothyroxine was the second most prescribed chronic drug after aspirin in the cohort (8.2%) and the third most prescribed when using Swiss-wide insurance data. In multivariable analysis, chronic levothyroxine use was associated with increasing age [odds ratio 1.03, 95% confidence interval 1.01-1.05 per 1-year increase]; female sex [11.87 (5.24-26.89)]; BMI [1.06 (1.02- 1.09) per 1-kg/m2 increase]; number of concomitant drugs [1.22 (1.16-1.29) per 1-drug increase]; and family history of thyroid pathologies [2.18 (1.37-3.48)]. Among chronic levothyroxine users with thyroid hormones assessment (n = 157), 42 (27%) were outside the TSH therapeutic range (17% overtreated and 10% undertreated). Conclusions In this population-based study, levothyroxine ranked second among chronic drugs. Age, female sex, BMI, number of drugs and family history of thyroid pathologies were associated with chronic levothyroxine use. More than one in four chronic users were over- or undertreated

The recent landscape history of Limpach valley, Switzerland: considering three empirical hypotheses on driving forces of landscape change

Understanding global landscape dynamics is a core challenge for the newly emerged field of land change science. Such an understanding requires insights into general pattern of landscape changes and the related driving forces. Many case studies of landscape change exist, but only few attempts have been made, to synthesize the results and to search for general pattern. We suggest that applying hypotheses on driving forces of landscape change derived from one case study in another region as a promising way to advance towards a more integrative view on landscape dynamics. Based on the conclusions drawn in a case study conducted in Godmanchester (Quebec, Canada; Domon and Bouchard 2007), we formulated three hypotheses and discussed them in a case study on landscape change in the Limpach valley, Switzerland. We confirm the importance of geomorphological characteristics for landscape development (hypothesis 1) and our analysis also supports the second hypothesis, which states that changes in demand for certain resources result in landscape change. However, we suggest replacing the term resources by the more encompassing concept of goods and services. The third hypothesis, which states that technological transformations stand at the beginning of landscape change, also was confirmed. Technologies have to be affordable, socially accepted, and corresponding to a demand, to be implemented on a large scale. This will cause a technological transformation, which then—depending on the specifics of the technology applied—becomes relevant for landscape development. We conclude with three reworded hypotheses on driving forces of landscape change and we hope that they will be tested and further developed in other case studie

Are local tax rates strategic complements or strategic substitutes?

The identification of strategic interactions among local governments is typically plagued by endogeneity problems. This paper proposes an identification strategy that makes use of a multi-tier federal system. State-level fiscal reforms provide an arguably exogenous source of variation in tax rates of local jurisdictions. Moreover, state borders spatially bound the effects of state-level fiscal reforms across areas that are otherwise highly integrated. Using the fact that local jurisdictions located close to a state border have some neighbors in another state, I propose to instrument the (average) tax rate of neighbor jurisdictions with the state-level tax rate of the neighboring state. I use this instrument to identify strategic personal income tax setting by local jurisdictions in Switzerland. In contrast to most of the existing empirical literature and to all results based on standard instruments, I find that tax rates are strategic substitutes in most cases. Tax rates are found to be strategic complements only in the context of large tax cuts

Caries Epidemiology and Community Dentistry: Chances for Future Improvements in Caries Risk Groups. Outcomes of the ORCA Saturday Afternoon Symposium, Greifswald, 2014. Part 1

This paper reviews the first part of the outcomes of the ORCA Saturday Afternoon Symposium 2014 dealing with ‘caries epidemiology and community dentistry: chances for future improvements in caries risk groups'. After the caries decline in many countries, there are remaining pockets of higher caries levels, mostly in the primary dentition and/or linked to a low socio-economic status (SES). The review into the evidence of caries-preventive measures clearly points to the use of fluorides, especially toothbrushing with fluoridated toothpaste and collective measures such as water fluoridation. In contrast to several unsuccessful high-risk approaches, community and public health programmes seem to be able to ensure a population-wide access and compliance in risk groups. Their simple and evidence-based measures mostly combine regular plaque removal and fluoride applications via toothbrushing, at least for children and adolescents. For the future, the common risk factor approach which addresses associations between oral health, social deprivation, diet, hygiene, smoking, alcohol use and stress should lead to combined efforts with other community health and education specialists. Further engagement with public policy, community leaders and administration is needed in order to strengthen healthy choices and behaviour, e.g. in ‘healthy' schools and kindergartens. It seems advisable that these population programmes also aim at improving upstream factors

Species richness and abundance of native leaf miners are affected by the presence of the invasive horse-chestnut leaf miner

The effect of the alien horse-chestnut leaf miner, Cameraria ohridella, on native fauna was studied by comparing the species richness of native leaf miner communities and the abundance of selected native leaf miner species in the presence and absence of horse-chestnut trees infested by C. ohridella, in various environments in Europe. The species richness of native leaf miner communities in Switzerland was lower at sites where C. ohridella was present than at control sites. In Switzerland, France and Bulgaria, several native leaf miner species were significantly less abundant in the vicinity of infested horse-chestnuts. The native species most affected by the presence of the invasive alien species were those occurring early in the year and sharing their parasitoid complex with C. ohridella. These results suggest apparent competition mediated by shared natural enemies because these are the only link between C. ohridella and native leaf miners using other food resource

How Effective Are Unemployment Benefit Sanctions? Looking Beyond Unemployment Exit

This paper provides a comprehensive evaluation of benefit sanctions, i.e. temporary reductions in unemployment benefits as punishment for noncompliance with eligibility requirements. In addition to the effects on unemployment durations, we evaluate the effects on post-unemployment employment stability, on exits from the labor market and on earnings. In our analysis we use a rich set of Swiss register data which allow us to distinguish between ex ante effects, the effects of warnings and the effects of enforcement of benefit sanctions. Adopting a multivariate mixed proportional hazard approach to address selectivity, we find that both warnings and enforcement increase the job finding rate and the exit rate out of the labor force. Warnings do not affect subsequent employment stability but do reduce post-unemployment earnings. Actual benefit reductions lower the quality of post-unemployment jobs both in terms of job duration as well as in terms of earnings. The net effect of a benefit sanction on post-unemployment income is negative. Over a period of two years after leaving unemployment workers who got a benefit sanction imposed face a net income loss equivalent to 30 days of full pay due to the ex post effect. In addition to that, stricter monitoring may reduce net earnings by up to 4 days of pay for every unemployed worker due to the ex ante effect.unemployment duration, earnings effects, benefit sanctions, competing-risk duration models

Coupled climate-glacier modelling of the last glaciation in the Alps

Our limited knowledge of the climate prevailing over Europe during former glaciations is the main obstacle to reconstruct the past evolution of the ice coverage over the Alps by numerical modelling. To address this challenge, we perform a two-step modelling approach: First, a regional climate model is used to downscale the time slice simulations of a global earth system model in high resolution, leading to climate snapshots during the Last Glacial Maximum (LGM) and the Marine Isotope Stage 4 (MIS4). Second, we combine these snapshots and a climate signal proxy to build a transient climate over the last glacial period and force the Parallel Ice Sheet Model to simulate the dynamical evolution of glaciers in the Alps. The results show that the extent of modelled glaciers during the LGM agrees with several independent key geological imprints, including moraine-based maximal reconstructed glacial extents, known ice transfluences and trajectories of erratic boulders of known origin and deposition. Our results highlight the benefit of multiphysical coupled climate and glacier transient modelling over simpler approaches to help reconstruct paleo glacier fluctuations in agreement with traces they have left on the landscape

Single-cell transcriptomics reveals striking heterogeneity and functional organization of dendritic and monocytic cells in the bovine mesenteric lymph node.

Dendritic and monocytic cells co-operate to initiate and shape adaptive immune responses in secondary lymphoid tissue. The complexity of this system is poorly understood, also because of the high phenotypic and functional plasticity of monocytic cells. We have sequenced mononuclear phagocytes in mesenteric lymph nodes (LN) of three adult cows at the single-cell level, revealing ten dendritic-cell (DC) clusters and seven monocyte/macrophage clusters with clearly distinct transcriptomic profiles. Among DC, we defined LN-resident subsets and their progenitors, as well as subsets of highly activated migratory DC differing in transcript levels for T-cell attracting chemokines. Our analyses also revealed a potential differentiation path for cDC2, resulting in a cluster of inflammatory cDC2 with close transcriptional similarity to putative DC3 and monocyte-derived DC. Monocytes and macrophages displayed sub-clustering mainly driven by pro- or anti-inflammatory expression signatures, including a small cluster of cycling, presumably self-renewing, macrophages. With this transcriptomic snapshot of LN-derived mononuclear phagocytes, we reveal functional properties and differentiation trajectories in a "command center of immunity", and identify elements that are conserved across species