Consumption-oriented policy instruments for fostering greenhouse gas mitigation

Most policy instruments to reduce greenhouse gas (GHG) emissions have focused on producers, and on the energy efficiency of buildings, vehicles and other products. Behavioural changes related to climate change also impact ‘in-use’ emissions, and potentially, emissions both ‘upstream’ (including from imported goods) and ‘downstream’ (eg disposal). Consumption-oriented policies may provide avenues to additional and cost-effective emission reductions, but are less prevalent, in part because of political sensitivities around government efforts to shape individual-level mitigation behaviour. In this paper, we explore policy instruments for encouraging low carbon behaviour in the EU context. Drawing on a literature survey and interviews, as part of the EU Carbon-CAP project, we develop a list of 33 potential instruments, present a systematic methodology for assessing their potential impact and feasibility, and apply this to rank instruments of most interest. Most instruments involve a clear trade-off between their potential impact and feasibility; about half feature in the top three scoring categories, many being voluntary approaches, which may be easier to implement, but with limited or highly uncertain impact. However, we identify a handful of top-scoring instruments that deserve far more policy attention. The complexity of consumer and corporate motivations and behaviours suggests that instruments should be trialled and monitored (e.g. in regions / individual States) before widespread introduction. Most would also be most effective when nested within wider policy packages, to address the varied behavioural motivations and stages of supply chains

The rising burden of spondylodiscitis in Germany: an epidemiologic study based on the federal statistical office database [Abstract]

Introduction: Spondylodiscitis is the commonest form of infectious disease of the spine and harbours a high mortality rate of up to 20%. Recent demographic trends in Germany, such as an aging population, immunosuppression, and intravenous drug use, suggest that the incidence of spondylodiscitis may be on the rise. However, the exact epidemiological development of the disease remains uncertain. This study aims to analyse the burden on the tertiary healthcare system in Germany using data from the Federal Statistical Office of Germany (FSOG) database. Materials and Methods: All cases of spondylodiscitis diagnosed between 2005 and 2021 were identified from the FSOG database. The study characterised the mean duration of hospital stays, total and population-adjusted number of diagnoses made, age-stratified incidence, and outcomes of hospitalised patients. Results: A total of 131,982 diagnoses for spondylodiscitis were identified between 2005 and 2021. The number of diagnoses for spondylodiscitis has doubled during this period, from 5.4/100,000 population in 2005 to 11/100,000 population in 2021. The highest increase in admissions was recorded for those aged 90 years and above (+1307%), 80-89 (+376%) and 70-79 (+99%). Hospital discharges to rehabilitation facilities have increased by 160%, and discharges against medical advice by 91%. On the other hand, during the analysed period, the in-hospital mortality rate has decreased by 52%. Conclusion: The population-adjusted incidence of spondylodiscitis in Germany has more than doubled between 2005 and 2021, highlighting the clinical relevance of this disease. During the same period, in-hospital mortality dropped by half. These findings suggest the need for further investigation into optimal therapy, particularly the role and timing of surgical treatment

Metformin and cimetidine: Physiologically based pharmacokinetic modelling to investigate transporter mediated drug–drug interactions

Metformin is used as a probe for OCT2 mediated transport when investigating possible DDIs with new chemical entities. The aim of the current study was to investigate the ability of physiologically-based pharmacokinetic (PBPK) models to simulate the effects of OCT and MATE inhibition by cimetidine on metformin kinetics. PBPK models were developed, incorporating mechanistic kidney and liver sub-models for metformin (OCT and MATE substrate) and a mechanistic kidney sub-model for cimetidine. The models were used to simulate inhibition of the MATE1, MATE2-K, OCT1 and OCT2 mediated transport of metformin by cimetidine. Assuming competitive inhibition and using cimetidine Ki values determined in vitro, the predicted metformin AUC ratio was 1.0 compared to an observed value of 1.46. The observed AUC ratio could only be recovered with this model when the cimetidine Ki for OCT2 was decreased 1000-fold or the Ki's for both OCT1 and OCT2 were decreased 500- fold. An alternative description of metformin renal transport by OCT1 and OCT2, incorporating electrochemical modulation of the rate of metformin uptake together with 8–18-fold decreases in cimetidine Ki's for OCTs and MATEs, allowed recovery of the extent of the observed effect of cimetidine on metformin AUC. While the final PBPK model has limitations, it demonstrates the benefit of allowing for the complexities of passive permeability combined with active cellular uptake modulated by an electrochemical gradient and active efflu

Judging Time-to-Passage of looming sounds: evidence for the use of distance-based information

Perceptual judgments are an essential mechanism for our everyday interaction with other moving agents or events. For instance, estimation of the time remaining before an object contacts or passes us is essential to act upon or to avoid that object. Previous studies have demonstrated that participants use different cues to estimate the time to contact or the time to passage of approaching visual stimuli. Despite the considerable number of studies on the judgment of approaching auditory stimuli, not much is known about the cues that guide listeners’ performance in an auditory Time-to-Passage (TTP) task. The present study evaluates how accurately participants judge approaching white-noise stimuli in a TTP task that included variable occlusion periods (portion of the presentation time where the stimulus is not audible). Results showed that participants were able to accurately estimate TTP and their performance, in general, was weakly affected by occlusion periods. Moreover, we looked into the psychoacoustic variables provided by the stimuli and analysed how binaural cues related with the performance obtained in the psychophysical task. The binaural temporal difference seems to be the psychoacoustic cue guiding participants’ performance for lower amounts of occlusion, while the binaural loudness difference seems to be the cue guiding performance for higher amounts of occlusion. These results allowed us to explain the perceptual strategies used by participants in a TTP task (maintaining accuracy by shifting the informative cue for TTP estimation), and to demonstrate that the psychoacoustic cue guiding listeners’ performance changes according to the occlusion period.This study was supported by: Bial FoundationGrant 143/14 (https://www.bial.com/en/bial_foundation.11/11th_symposium.219/ fellows_preliminary_results.235/fellows_ preliminary_results.a569.html); FCT PTDC/EEAELC/112137/2009 (https://www.fct.pt/apoios/projectos/consulta/vglobal_projecto?idProjecto=112137&idElemConcurso=3628); and COMPETE: POCI-01-0145-FEDER-007043 and FCT – Fundação para a Ciência e Tecnologia within the Project Scope: UID/CEC/00319/2013.info:eu-repo/semantics/publishedVersio

PBMCs transcriptome profiles identified breed-specific transcriptome signatures for PRRSV vaccination in German Landrace and Pietrain pigs

Porcine reproductive and respiratory syndrome (PRRS) is a devastating viral disease affecting the swine industry worldwide. Genetic variation in host immunity has been considered as one of the potential determinants to improve the immunocompetence, thereby resistance to PRRS. Therefore, the present study aimed to investigate the breed difference in innate immune response to PRRSV vaccination between German Landrace (DL) and Pietrain (Pi) pigs. We analyzed microarray-based transcriptome profiles of peripheral blood mononuclear cells (PBMCs) collected before (0 h) and 24 h after PRRSV vaccination from purebred DL and Pi pigs with three biological replicates. In total 4,269 transcripts were identified to be differentially expressed in PBMCs in at least any of four tested contrast pairs (i.e. DL-24h vs. DL-0h, Pi-24h vs. Pi-0h, DL-0h vs. Pi-0h and DL-24h vs. Pi-24h). The number of vaccine-induced differentially expressed genes (DEGs) was much higher (2,459) in DL pigs than that of Pi pigs (291). After 24 h of PRRSV vaccination, 1,046 genes were differentially expressed in PMBCs of DL pigs compared to that of Pi (DL-24h vs. Pi-24h), indicating the breed differences in vaccine responsiveness. The top biological pathways significantly affected by DEGs of both breeds were linked to immune response functions. The network enrichment analysis identified ADAM17, STAT1, MMS19, RPA2, BAD, UCHL5 and APC as potential regulatory genes for the functional network of PRRSV vaccine response specific for DL; while FOXO3, IRF2, ADRBK1, FHL3, PPP2CB and NCOA6 were found to be the most potential hubs of Pi specific transcriptome network. In conclusion, our data provided insights of breed-specific host transcriptome responses to PRRSV vaccination which might contribute in better understanding of PPRS resistance in pigs