A multicentre, patient- and assessor-blinded, non-inferiority, randomised and controlled phase II trial to compare standard and torque teno virus-guided immunosuppression in kidney transplant recipients in the first year after transplantation:TTVguideIT

Background: Immunosuppression after kidney transplantation is mainly guided via plasma tacrolimus trough level, which cannot sufficiently predict allograft rejection and infection. The plasma load of the non-pathogenic and highly prevalent torque teno virus (TTV) is associated with the immunosuppression of its host. Non-interventional studies suggest the use of TTV load to predict allograft rejection and infection. The primary objective of the current trial is to demonstrate the safety, tolerability and preliminary efficacy of TTV-guided immunosuppression. Methods: For this purpose, a randomised, controlled, interventional, two-arm, non-inferiority, patient- and assessor-blinded, investigator-driven phase II trial was designed. A total of 260 stable, low-immunological-risk adult recipients of a kidney graft with tacrolimus-based immunosuppression and TTV infection after month 3 post-transplantation will be recruited in 13 academic centres in six European countries. Subjects will be randomised in a 1:1 ratio (allocation concealment) to receive tacrolimus either guided by TTV load or according to the local centre standard for 9 months. The primary composite endpoint includes the occurrence of infections, biopsy-proven allograft rejection, graft loss, or death. The main secondary endpoints include estimated glomerular filtration rate, graft rejection detected by protocol biopsy at month 12 post-transplantation (including molecular microscopy), development of de novo donor-specific antibodies, health-related quality of life, and drug adherence. In parallel, a comprehensive biobank will be established including plasma, serum, urine and whole blood. The date of the first enrolment was August 2022 and the planned end is April 2025. Discussion: The assessment of individual kidney transplant recipient immune function might enable clinicians to personalise immunosuppression, thereby reducing infection and rejection. Moreover, the trial might act as a proof of principle for TTV-guided immunosuppression and thus pave the way for broader clinical applications, including as guidance for immune modulators or disease-modifying agents.</p

The masterpieces of John Forbes Nash Jr.

In this set of notes I follow Nash’s four groundbreaking works on real algebraic manifolds, on isometric embeddings of Riemannian manifolds and on the continuity of solutions to parabolic equations. My aim has been to stay as close as possible to Nash’s original arguments, but at the same time present them with a more modern language and notation. Occasionally I have also provided detailed proofs of the points that Nash leaves to the reader

Shifting the limits in wheat research and breeding using a fully annotated reference genome

Introduction: Wheat (Triticum aestivum L.) is the most widely cultivated crop on Earth, contributing about a fifth of the total calories consumed by humans. Consequently, wheat yields and production affect the global economy, and failed harvests can lead to social unrest. Breeders continuously strive to develop improved varieties by fine-tuning genetically complex yield and end-use quality parameters while maintaining stable yields and adapting the crop to regionally specific biotic and abiotic stresses. Rationale: Breeding efforts are limited by insufficient knowledge and understanding of wheat biology and the molecular basis of central agronomic traits. To meet the demands of human population growth, there is an urgent need for wheat research and breeding to accelerate genetic gain as well as to increase and protect wheat yield and quality traits. In other plant and animal species, access to a fully annotated and ordered genome sequence, including regulatory sequences and genome-diversity information, has promoted the development of systematic and more time-efficient approaches for the selection and understanding of important traits. Wheat has lagged behind, primarily owing to the challenges of assembling a genome that is more than five times as large as the human genome, polyploid, and complex, containing more than 85% repetitive DNA. To provide a foundation for improvement through molecular breeding, in 2005, the International Wheat Genome Sequencing Consortium set out to deliver a high-quality annotated reference genome sequence of bread wheat. Results: An annotated reference sequence representing the hexaploid bread wheat genome in the form of 21 chromosome-like sequence assemblies has now been delivered, giving access to 107,891 high-confidence genes, including their genomic context of regulatory sequences. This assembly enabled the discovery of tissue- and developmental stage–related gene coexpression networks using a transcriptome atlas representing all stages of wheat development. The dynamics of change in complex gene families involved in environmental adaptation and end-use quality were revealed at subgenome resolution and contextualized to known agronomic single-gene or quantitative trait loci. Aspects of the future value of the annotated assembly for molecular breeding and research were exemplarily illustrated by resolving the genetic basis of a quantitative trait locus conferring resistance to abiotic stress and insect damage as well as by serving as the basis for genome editing of the flowering-time trait. Conclusion: This annotated reference sequence of wheat is a resource that can now drive disruptive innovation in wheat improvement, as this community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding. Importantly, the bioinformatics capacity developed for model-organism genomes will facilitate a better understanding of the wheat genome as a result of the high-quality chromosome-based genome assembly. By necessity, breeders work with the genome at the whole chromosome level, as each new cross involves the modification of genome-wide gene networks that control the expression of complex traits such as yield. With the annotated and ordered reference genome sequence in place, researchers and breeders can now easily access sequence-level information to precisely define the necessary changes in the genomes for breeding programs. This will be realized through the implementation of new DNA marker platforms and targeted breeding technologies, including genome editing

Empirical antimicrobial treatment in haemato-/oncological patients with neutropenic sepsis

Neutropenic sepsis in haemato-/oncological patients is a medical emergency, as infections may show a fulminant clinical course. Early differentiation between sepsis and febrile neutropenic response often proves to be challenging. To assess the severity of the illness, different tools, which are discussed in this article, are available. Once the diagnosis has been established, the correct use of early empirical antibiotic and antifungal treatment is key in improving patient survival. Therefore, profound knowledge of local resistance patterns is mandatory and carefully designed antibiotic regimens have to be established in cooperation with local microbiologists or infectious diseases specialists. In the following, identification, therapy and management of high-risk, neutropenic patients will be reviewed based on experimental and clinical studies, guidelines and reviews.(VLID)468376

TOWARDS WEB 2.0 DRIVEN LEARNING ENVIRONMENTS

Over the last decade, it has been widely argued that technology-enhanced learning could respond to the needs of the new knowledge society and transform the way we learn. However, despite isolated achievements, technology-enhanced learning has not really succeeded yet in revolutionizing our education and learning processes. In fact, most current initiatives do not focus on the social aspect of learning and learning content is still pushed to a pre-defined group of learners in closed environments. Recently, Web 2.0 concepts have started to open new doors for more effective learning and have the potential to overcome many of the limitations of traditional learning models. In this paper we show in which way the communitydriven platform Learnr, under development at the University of Münster, puts crucial success factors for future technology enhanced learning into practice, applying well known concepts like networking and social tagging. As a consequence, a Web 2.0 perspective on learners, learning content and learning communities can be derived.

The SYBR Green I Malaria Drug Sensitivity Assay: Performance in Low Parasitemia Samples

Validation of the sensitivity of the SYBR Green I in vitro test against an enzyme-linked immunosorbent assay (ELISA)-based drug sensitivity assay. Our results suggest that the SYBR Green I assay is a fast and inexpensive malaria drug screening assay for laboratory use. However, because of its lack of sensitivity in whole blood samples its usefulness for testing clinical samples may be limited

Incubation of bacteria with PRF ± antimicrobial agent—Methods.

<p>Incubation of bacteria with PRF ± antimicrobial agent—Methods.</p