Improving sample efficiency and multi-agent communication in RL-based train rescheduling

We present preliminary results from our sixth placed entry to the Flatland international competition for train rescheduling, including two improvements for optimized reinforcement learning (RL) training efficiency, and two hypotheses with respect to the prospect of deep RL for complex real-world control tasks: first, that current state of the art policy gradient methods seem inappropriate in the domain of high-consequence environments; second, that learning explicit communication actions (an emerging machine-to-machine language, so to speak) might offer a remedy. These hypotheses need to be confirmed by future work. If confirmed, they hold promises with respect to optimizing highly efficient logistics ecosystems like the Swiss Federal Railways railway network

Patient-Specific Three-Dimensional Composite Bone Models for Teaching and Operation Planning

Background: Orthopedic trauma care relies on two-dimensional radiograms both before and during the operation. Understanding the three-dimensional nature of complex fractures on plain radiograms is challenging. Modern fluoroscopes can acquire three-dimensional volume datasets even during an operation, but the device limitations constrain the acquired volume to a cube of only 12-cm edge. However, viewing the surrounding intact structures is important to comprehend the fracture in its context. We suggest merging a fluoroscope's volume scan into a generic bone model to form a composite full-length 3D bone model. Methods: Materials consisted of one cadaver bone and 20 three-dimensional surface models of human femora. Radiograms and computed tomography scans were taken before and after applying a controlled fracture to the bone. A 3D scan of the fracture was acquired using a mobile fluoroscope (Siemens Siremobil). The fracture was fitted into the generic bone models by rigid registration using a modified least-squares algorithm. Registration precision was determined and a clinical appraisal of the composite models obtained. Results: Twenty composite bone models were generated. Average registration precision was 2.0mm (range 1.6 to 2.6). Average processing time on a laptop computer was 35s (range 20 to 55). Comparing synthesized radiograms with the actual radiograms of the fractured bone yielded clinically satisfactory results. Conclusion: A three-dimensional full-length representation of a fractured bone can reliably be synthesized from a short scan of the patient's fracture and a generic bone model. This patient-specific model can subsequently be used for teaching, surgical operation planning, and intraoperative visualization purpose

Draft Genome Sequences of Enterococcus mundtii Strains Isolated from Beef Slaughterhouses in Kenya

We present here draft genome sequences of Enterococcus mundtii strains K7-EM, P2-EM, C11-EM, and H18-EM, which were isolated from slaughterhouse equipment, carcasses, and personnel of small- and medium-sized beef slaughterhouses in Kenya

Cytomegalovirus and polyomavirus BK posttransplant

Virus replication and progression to disease in transplant patients is determined by patient-, graft- and virus-specific factors. This complex interaction is modulated by the net state of immunosuppression and its impact on virus-specific cellular immunity. Due to the increasing potency of immunosuppressive regimens, graft rejections have decreased, but susceptibility to infections has increased. Therefore, cytomegalovirus (CMV) remains the most important viral pathogen posttransplant despite availability of effective antiviral drugs and validated strategies for prophylactic, preemptive and therapeutic intervention. CMV replication can affect almost every organ system, with frequent recurrences and increasing rates of antiviral resistance. Together with indirect long-term effects, CMV significantly reduces graft and patient survival after solid organ and hematopoietic stem cell transplantation. The human polyomavirus called BK virus (BKV), on the other hand, only recently surfaced as pathogen with organ tropism largely limited to the reno-urinary tract, manifesting as polyomavirus-associated nephropathy in kidney transplant and hemorrhagic cystitis in hematopoetic stem cell transplant patients. No licensed anti-polyoma viral drugs are available, and treatment relies mainly on improving immune functions to regain control over BKV replication. In this review, we discuss diagnostic and therapeutic aspects of CMV and BKV replication and disease posttransplantatio

Tuberculosis in Times of War and Peace

This chapter provides a comprehensive analysis of tuberculosis (TB) across different historical contexts of war and peace, underscoring the disease’s resilience and adaptability. It highlights the exacerbation of TB transmission due to war-related factors such as mass displacement, malnutrition, and compromised healthcare systems, while also noting periods of peace as opportunities for advancing TB control measures. The chapter examines the impact of major conflicts on TB incidence and management, including World Wars I and II and more recent conflicts like the Ukraine war. It also discusses the evolution of TB control efforts, from the discovery of Mycobacterium tuberculosis to modern strategies against drug-resistant TB, emphasizing the importance of international collaboration and integrated public health strategies to combat this enduring global health challenge

Prevalence of Polyomavirus BK and JC Infection and Replication in 400 Healthy Blood Donors

BackgroundThe replication of BK virus (BKV) and JC virus (JCV) is linked to polyomavirus-associated nephropathy, hemorrhagic cystitis, and multifocal leukoencephalopathy in immunodeficient patients, but the behavior of these viruses in immunocompetent individuals has hardly been characterized MethodsWe used EIA to study samples obtained from 400 healthy blood donors aged 20-59 years for BKV- and JCV-specific antibodies against virus-like particles. We also studied BKV and JCV loads in plasma and urine among these individuals by use of real-time polymerase chain reaction ResultsIgG seroprevalence was 82% (328 of 400 donors) for BKV and 58% (231 of 400) for JCV. As age increased (age groups were divided by decade), the seroprevalence of BKV decreased from 87% (87 of 100) in the youngest group (aged 20-29 years) to 71% (71 of 100) in the oldest group (aged 50-59 years) (P=.006), whereas the seroprevalence of JCV increased from 50% (50 of 100) in the youngest group to 68% (68 of 100) in the oldest group (P=.06). Asymptomatic urinary shedding of BKV and JCV was observed in 28 (7%) and 75 (19%) of 400 subjects, respectively, with median viral loads of 3.51 and 4.64 log copies/mL, respectively (P<.001). Unlike urinary BKV loads, urinary JCV loads were positively correlated with IgG levels. The shedding of JCV was more commonly observed among individuals who were seropositive only for JCV, compared with individuals who were seropositive for both BKV and JCV, suggesting limited cross-protection from BKV immunity. Noncoding control regions were of archetype architecture in all cases, except for 1 rearranged JCV variant. Neither BKV nor JCV DNA was detected in plasma ConclusionsOur study provides important data about polyomavirus infection and replication in healthy, immunocompetent individuals. These data indicate significant differences between BKV and JCV with respect to virus-host interaction and epidemiolog

Combination of Whole Genome Sequencing and Metagenomics for Microbiological Diagnostics

Whole genome sequencing (WGS) provides the highest resolution for genome-based species identification and can provide insight into the antimicrobial resistance and virulence potential of a single microbiological isolate during the diagnostic process. In contrast, metagenomic sequencing allows the analysis of DNA segments from multiple microorganisms within a community, either using an amplicon- or shotgun-based approach. However, WGS and shotgun metagenomic data are rarely combined, although such an approach may generate additive or synergistic information, critical for, e.g., patient management, infection control, and pathogen surveillance. To produce a combined workflow with actionable outputs, we need to understand the pre-to-post analytical process of both technologies. This will require specific databases storing interlinked sequencing and metadata, and also involves customized bioinformatic analytical pipelines. This review article will provide an overview of the critical steps and potential clinical application of combining WGS and metagenomics together for microbiological diagnosis

Effect of Immunosuppression on T-Helper 2 and B-Cell Responses to Influenza Vaccination

Background. Influenza vaccine immunogenicity is suboptimal in immunocompromised patients. However, there are limited data on the interplay of T- and B- cell responses to vaccination with simultaneous immunosuppression. Methods. We collected peripheral blood mononuclear cells from transplant recipients before and 1 month after seasonal influenza vaccination. Before and after vaccination, H1N1-specific T- and B-cell activation were quantified with flow cytometry. We also developed a mathematical model using T- and B-cell markers and mycophenolate mofetil (MMF) dosage. Results. In the 47 patients analyzed, seroconversion to H1N1 antigen was demonstrated in 34%. H1N1-specific interleukin 4 (IL-4)-producing CD4+ T-cell frequencies increased significantly after vaccination in 53% of patients. Prevaccine expression of H1N1-induced HLA-DR and CD86 on B cells was high in patients who seroconverted. Seroconversion against H1N1 was strongly associated with HLA-DR expression on B cells, which was dependent on the increase between prevaccine and postvaccine H1N1-specific IL-4+CD4+ T cells (R2 = 0.35). High doses of MMF (≥2 g/d) led to lower seroconversion rates, smaller increase in H1N1-specific IL-4+CD4+ T cells, and reduced HLA-DR expression on B cells. The mathematical model incorporating a MMF-inhibited positive feedback loop between H1N1-specific IL-4+CD4+ T cells and HLA-DR expression on B cells captured seroconversion with high specificity. Conclusions. Seroconversion is associated with influenza-specific T-helper 2 and B-cell activation and seems to be modulated by MM

Immunomodulatory Function of Interleukin 28B During Primary Infection With Cytomegalovirus

Background. Feedback mechanisms between interferons α and λ (IFNs) may be affected by single nucleotide polymorphisms (SNP) in interleukin 28B (IL-28B; IFN-λ3) promoter region and may influence cytomegalovirus (CMV) replication. Methods. We associated IL-28B SNPs with the risk of CMV replication after transplantation. Next, we examined the effect of IL-28B genotypes on IL-28B, and IFN-stimulated gene (ISG) expression, and CMV replication in human foreskin fibroblast (HFF) and peripheral blood mononuclear cells (PBMCs). Results. Transplant recipients with an IL-28B SNP (rs8099917) had significantly less CMV replication (P = .036). Both HFF-cells and PBMCs with a SNP showed lower IL-28B expression during infection with CMV, but higher "antiviral” ISG expression (eg, OAS1). Fibroblasts with a SNP had a 3-log reduction of CMV replication at day 4 (P = .004). IL-28B pretreatment induced ISG expression in noninfected fibroblasts, but a relative decrease of ISG expression could be observed in CMV-infected fibroblasts. The inhibitory effects of IL-28B could be abolished by siRNA or antagonistic peptides against the IL-28 receptor. In fibroblasts, inhibition of IL-28 signaling resulted in an increase of ISG expression and 3-log reduction of CMV-replication (P = .01). Conclusions. We postulate that IL-28B may act as a key regulator of ISG expression during primary CMV infection. IL-28B SNPs may be associated with higher antiviral ISG expression, which results in better replication contro