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Purpose – Like a well-designed procurement strategy, a well-designed rolling stock strategy promotes the development of a railroad company and contributes to its competitive advantage. Effective implementation of the rolling stock strategy enhances the likelihood of enjoying the benefits of the strategy’s design. A successful implementation relies on the strategy being known, understood, controlled and communicated to the entire organization. Design/methodology/approach – The research consists of an extensive literature review as well as a series of workshops with rolling stock suppliers, railway authorities and representatives and rail users. Findings – This paper presents a collection of solutions for passenger rail rolling stock procurement. The authors offer guidance to the strategic procurement of rolling stock in the European Union (EU) and propose key performance indicators to measure the effectiveness of a rolling stock strategy. Research limitations/implications – While this study presents a thorough evaluation of rolling stock procurement practices, it is limited by its geographic isolation. Future studies should compare the procurement practices discussed here to others in the EU, as well as in North America, South America and Asia. Additionally, this study focused on the passenger rail segment. Passenger transport is an important function of the rail network in the EU, but future research should expand the assessment of rolling stock procurement strategies to freight rail as well. Originality/value – Overall, this work provides visibility into common rolling stock procurement practices in complex EU railway markets. This work expands the literature through a review of these practices and through enabling research into best practices or a commonly accepted procurement model.

Gasdermins (GSDMs) share a common functional domain structure and are best known for their capacity to form membrane pores. These pores are hallmarks of a specific form of cell death called pyroptosis and mediate the secretion of pro-inflammatory cytokines such as interleukin 1β (IL1β) and interleukin 18 (IL18). Thereby, Gasdermins have been implicated in various immune responses against cancer and infectious diseases such as acute Salmonella Typhimurium (S.Tm) gut infection. However, to date, we lack a comprehensive functional assessment of the different Gasdermins (GSDMA-E) during S.Tm infection in vivo. Here, we used epithelium-specific ablation, bone marrow chimeras, and mouse lines lacking individual Gasdermins, combinations of Gasdermins or even all Gasdermins (GSDMA1-3C1-4DE) at once and performed littermate-controlled oral S.Tm infections in streptomycin-pretreated mice to investigate the impact of all murine Gasdermins. While GSDMA, C, and E appear dispensable, we show that GSDMD i) restricts S.Tm loads in the gut tissue and systemic organs, ii) controls gut inflammation kinetics, and iii) prevents epithelium disruption by 72 h of the infection. Full protection requires GSDMD expression by both bone-marrow-derived lamina propria cells and intestinal epithelial cells (IECs). In vivo experiments as well as 3D-, 2D-, and chimeric enteroid infections further show that infected IEC extrusion proceeds also without GSDMD, but that GSDMD controls the permeabilization and morphology of the extruding IECs, affects extrusion kinetics, and promotes overall mucosal barrier capacity. As such, this work identifies a unique multipronged role of GSDMD among the Gasdermins for mucosal tissue defense against a common enteric pathogen.

PurposeThe Multicentre Acute ischemic stroke imaGIng and Clinical data (MAGIC) repository is a collaboration established in 2024 by seven stroke centres in Europe. MAGIC consolidates clinical and radiological data from acute ischemic stroke (AIS) patients who underwent endovascular therapy, intravenous thrombolysis, a combination of both, or conservative management.ParticipantsAll centres ensure accuracy and completeness of the data. Only patients who did not refuse use of their routine data collected during or after their hospital stay are included in the repository. Approvals or waivers are obtained from the responsible ethics committees before data exchange. A formal data transfer agreement (DTA) is signed by all contributing centres. The centres then share their data, and files are stored centrally on a safe server at the University Hospital Zurich. There, patient identifiers are removed and images are algorithmically de-faced. De-identified structured clinical data are connected to the imaging data by a new identifier. Data are made available to participating centres which have entered into a DTA for stroke research projects.Repository setupInitially, MAGIC is set to comprise initial and first follow-up imaging of 2,500 AIS patients. Clinical data consist of a comprehensive set of patient characteristics and routine prehospital metrics, treatment and laboratory variables.OutlookOur repository will support research by leveraging the entire range of routinely collected imaging and clinical data. This dataset reflects the current state of practice in stroke patient evaluation and management and will enable researchers to retrospectively study clinically relevant questions outside the scope of randomized controlled clinical trials. New centres are invited to join MAGIC if they meet the requirements outlined here. We aim to reach approximately 10,000 cases by 2026.

Purpose: To investigate the clinical outcomes of micropulse transscleral laser therapy (MP-TLT) in a cohort of glaucoma patients, including safety profile, post-operative transient intraocular pressure (IOP) spikes, long-term efficacy and prognostic factors in terms of IOP-lowering. Methods: This was a retrospective observational cohort study. Medical records of all patients who consecutively underwent MP-TLT between May 2019 and February 2023 at a tertiary referral centre were scrutinised and relevant data were retrospectively analysed. Results: A total of 131 patients (138 eyes) with a mean age of 73.2 ± 14.2 years were included. Mean pre-interventional IOP was 24.1 ± 9.1 mmHg. Within 6–12 h following the intervention on the same day, an IOP spike was regularly observed, reaching on average 31.7 ± 10.3 mmHg (p

Recruitment of neutrophils into and across the gut mucosa is a cardinal feature of intestinal inflammation in response to enteric infections. Previous work using the model pathogen Salmonella enterica serovar Typhimurium (S.Tm) established that invasion of intestinal epithelial cells by S.Tm leads to recruitment of neutrophils into the gut lumen, where they can reduce pathogen loads transiently. Notably, a fraction of the pathogen population can survive this defense, re-grow to high density, and continue triggering enteropathy. However, the functions of intraluminal neutrophils in the defense against enteric pathogens and their effects on preventing or aggravating epithelial damage are still not fully understood. Here, we address this question via neutrophil depletion in different mouse models of Salmonella colitis, which differ in their degree of enteropathy. In an antibiotic pretreated mouse model, neutrophil depletion by an anti-Ly6G antibody exacerbated epithelial damage. This could be linked to compromised neutrophil-mediated elimination and reduced physical blocking of the gut-luminal S.Tm population, such that the pathogen density remained high near the epithelial surface throughout the infection. Control infections with a ssaV mutant and gentamicin-mediated elimination of gut-luminal pathogens further supported that neutrophils are protecting the luminal surface of the gut epithelium. Neutrophil depletion in germ-free and gnotobiotic mice hinted that the microbiota can modulate the infection kinetics and ameliorate epithelium-disruptive enteropathy even in the absence of neutrophil-protection. Together, our data indicate that the well-known protective effect of the microbiota is augmented by intraluminal neutrophils. After antibiotic-mediated microbiota disruption, neutrophils are central for maintaining epithelial barrier integrity during acute Salmonella-induced gut inflammation, by limiting the sustained pathogen assault on the epithelium in a critical window of the infection.

Assessing the capacity of numerical models to produce viable tropical cyclones, as well as assessing the climatological behavior of simulated tropical cyclones, requires an objective tracking method. These make use of parameter thresholds to determine whether a detected feature, such as a vorticity maximum or a warm core, is strong enough to indicate a tropical cyclone. The choice of parameter thresholds is generally subjective. This study proposes and assesses the parallel use of many threshold parameter combinations, combining a number of weaker and stronger values. The tracking algorithm succeeds in tracking tropical cyclones within the model data, beginning at their aggregation stage or shortly thereafter and ending when they interact strongly with extratropical flow and transition into extratropical cyclones or when their warm core decays. The sensitivity of accumulated cyclone energy to tracking errors is assessed. Tracking errors include the faulty initial detection and termination of valid tropical cyclones and systems falsely identified as tropical cyclones. They are found to not significantly impact the accumulated cyclone energy. Thus, the tracking algorithm produces an adequate estimate of the accumulated cyclone energy within the underlying data.

Summary: Salmonella Typhimurium (S.Tm) utilizes the chemotaxis receptor Tsr to exploit gut inflammation. However, the characteristics of this exploitation and the mechanism(s) employed by the pathogen to circumvent antimicrobial effects of inflammation are poorly defined. Here, using different naturally occurring S.Tm strains (SL1344 and 14028) and competitive infection experiments, we demonstrate that type-three secretion system (T3SS)-2 virulence is indispensable for the beneficial effects of Tsr-directed chemotaxis. The removal of the 14028-specific prophage Gifsy3, encoding virulence effectors, results in the loss of the Tsr-mediated fitness advantage in that strain. Surprisingly, without T3SS-2 effector secretion, chemotaxis toward the gut epithelium using Tsr becomes disadvantageous for either strain. Our findings reveal that luminal neutrophils recruited as a result of NLRC4 inflammasome activation locally counteract S.Tm cells exploiting the byproducts of the host immune response. This work highlights a mechanism by which S.Tm exploitation of gut inflammation for colonization relies on the coordinated effects of chemotaxis and T3SS activities.