Gaining Momentum. How ECLI Improves Access to Case Law in Europe

In December 2010 the Council of the European Union adopted the conclusions on the European Case Law Identifier (ECLI). This paper examines the state of play regarding its implementation within the EU Member States and at European Courts. It also takes a closer look at the ECLI Search Engine which is now available on the European e-Justice portal and gives access to more than five million court decisions from twelve jurisdictions. But the ECLI Search Engine offers more than just a huge repository: it facilitates substantial and maybe even radical opportunities to further improve cross-border access to case law. Technology can be of help, but judiciaries have to contribute as well.

Genome-wide saturation mutagenesis of Burkholderia pseudomallei K96243 predicts essential genes and novel targets for antimicrobial development.

UNLABELLED: Burkholderia pseudomallei is the causative agent of melioidosis, an often fatal infectious disease for which there is no vaccine. B. pseudomallei is listed as a tier 1 select agent, and as current therapeutic options are limited due to its natural resistance to most antibiotics, the development of new antimicrobial therapies is imperative. To identify drug targets and better understand the complex B. pseudomallei genome, we sought a genome-wide approach to identify lethal gene targets. As B. pseudomallei has an unusually large genome spread over two chromosomes, an extensive screen was required to achieve a comprehensive analysis. Here we describe transposon-directed insertion site sequencing (TraDIS) of a library of over 10(6) transposon insertion mutants, which provides the level of genome saturation required to identify essential genes. Using this technique, we have identified a set of 505 genes that are predicted to be essential in B. pseudomallei K96243. To validate our screen, three genes predicted to be essential, pyrH, accA, and sodB, and a gene predicted to be nonessential, bpss0370, were independently investigated through the generation of conditional mutants. The conditional mutants confirmed the TraDIS predictions, showing that we have generated a list of genes predicted to be essential and demonstrating that this technique can be used to analyze complex genomes and thus be more widely applied. IMPORTANCE: Burkholderia pseudomallei is a lethal human pathogen that is considered a potential bioterrorism threat and has limited treatment options due to an unusually high natural resistance to most antibiotics. We have identified a set of genes that are required for bacterial growth and thus are excellent candidates against which to develop potential novel antibiotics. To validate our approach, we constructed four mutants in which gene expression can be turned on and off conditionally to confirm that these genes are required for the bacteria to survive

Specialised Government Publishing: the Law Pocket and Linked Legal Data in the Netherlands

In the Netherlands an infrastructure for collecting, linking and disseminating legal public data is gradually being created. One of the first end-user applications built on this infrastructure is the Law Pocket: a free app with which government officials, lawyers, students and citizens have the up-to-date legislation from the national and regional level always at hand. It gives access to more than 3,400 automatically updated law books, containing full texts and linked resources. The app also gives access to a growing number of manually composed books on specific topics, edited and annotated by specialised civil servants. The backgrounds of this linked data project are described, as well as the main components of the architecture and the functionalities of the Law Pocket. Also its use, future work and position on the legal information market are discusse

Online Publication of Court Decisions in Europe

Although nowadays most courts publish decisions on the internet, substantial differences exist between European countries regarding such publication. These differences not only pertain to the extent with which judgments are published and anonymised, but also to their metadata, searchability and reusability. This article, written by Marc van Opijnen, Ginevra Peruginelli, Eleni Kefali and Monica Palmirani, contains a synthesis of a comprehensive comparative study on the publication of court decisions within all Member States of the European Union. Specific attention is paid on the legal and policy frameworks governing case law publication, actual practices, data protection issues, Open Data policies as well as the state of play regarding the implementation of the European Case Law Identifier

On the concept of relevance in legal information retrieval

The concept of 'relevance' is crucial to legal information retrieval, but because of its intuitive understanding it goes undefined too easily and unexplored too often. We discuss a conceptual framework on relevance within legal information retrieval, based on a typology of relevance dimensions used within general information retrieval science, but tailored to the specific features of legal information. This framework can be used for the development and improvement of legal information retrieval systems

The role of molecular biomarkers in recurrent glioblastoma trials:an assessment of the current trial landscape of genome-driven oncology

For glioblastoma patients, the efficacy-targeted therapy is limited to date. Most of the molecular therapies previously studied are lacking efficacy in this population. More trials are needed to study the actual actionability of biomarkers in (recurrent) glioblastoma. This study aimed to assess the current clinical trial landscape to assess the role of molecular biomarkers in trials on recurrent glioblastoma treatment. The database ClinicalTrials.gov was used to identify not yet completed clinical trials on recurrent glioblastoma in adults. Recruiting studies were assessed to investigate the role of molecular criteria, which were retrieved as detailed as possible. Primary outcome was molecular criteria used as selection criteria for study participation. Next to this, details on moment and method of testing, and targets and drugs studied, were collected. In 76% (181/237) of the included studies, molecular criteria were not included in the study design. Of the remaining 56 studies, at least one specific genomic alteration as selection criterium for study participation was required in 33 (59%) studies. Alterations in EGFR, CDKN2A/B or C, CDK4/6, and RB were most frequently investigated, as were the corresponding drugs abemaciclib and ribociclib. Of the immunotherapies, CAR-T therapies were the most frequently studied therapies. Previously, genomics studies have revealed the presence of potentially actionable alterations in glioblastoma. Our study shows that the potential efficacy of targeted treatment is currently not translated into genome-driven trials in patients with recurrent glioblastoma. An intensification of genome-driven trials might help in providing evidence for (in)efficacy of targeted treatments.</p

Diagnostics and treatment delay in primary central nervous system lymphoma:What the neurosurgeon should know

Purpose: The gold standard for diagnostics in primary central nervous system lymphoma (PCNSL) is histopathological diagnosis after stereotactic biopsy. Yet, PCNSL has a multidisciplinary diagnostic work up, which associated with diagnostic delay and could result in treatment delay. This article offers recommendations to neurosurgeons involved in clinical decision-making regarding (novel) diagnostics and care for patients with PCNSL with the aim to improve uniformity and timeliness of the diagnostic process for patients with PCNSL. Methods: We present a mini review to discuss the role of stereotactic biopsy in the context of novel developments in diagnostics for PCNSL, as well as the role for cytoreductive surgery. Results: Cerebrospinal fluid-based diagnostics are supplementary and cannot replace stereotactic biopsy-based diagnostics. Conclusion: Histopathological diagnosis after stereotactic biopsy of the brain remains the gold standard for diagnosis. Additional diagnostics should not be a cause of diagnostic delay. There is currently no sufficient evidence supporting cytoreductive surgery in PCNSL, with recent studies showing contradictive data and suboptimal study designs.</p

Genome-Scale Identification of Resistance Functions in Pseudomonas aeruginosa Using Tn-seq

We describe a deep-sequencing procedure for tracking large numbers of transposon mutants of Pseudomonas aeruginosa. The procedure employs a new Tn-seq methodology based on the generation and amplification of single-strand circles carrying transposon junction sequences (the Tn-seq circle method), a method which can be used with virtually any transposon. The procedure reliably identified more than 100,000 transposon insertions in a single experiment, providing near-saturation coverage of the genome. To test the effectiveness of the procedure for mutant identification, we screened for mutations reducing intrinsic resistance to the aminoglycoside antibiotic tobramycin. Intrinsic tobramycin resistance had been previously analyzed at genome scale using mutant-by-mutant screening and thus provided a benchmark for evaluating the new method. The new Tn-seq procedure identified 117 tobramycin resistance genes, the majority of which were then verified with individual mutants. The group of genes with the strongest mutant phenotypes included nearly all (13 of 14) of those with strong mutant phenotypes identified in the previous screening, as well as a nearly equal number of new genes. The results thus show the effectiveness of the Tn-seq method in defining the genetic basis of a complex resistance trait of P. aeruginosa and indicate that it can be used to analyze a variety of growth-related processes

A genetic assay for gene essentiality in Clostridium

Essential genes of pathogens are potential therapeutic targets, but are difficult to verify. Here, gene essentiality was determined by targeted knockout following engineered gene duplication. Null mutants of candidate essential genes of Clostridium difficile were viable only in the presence of a stable second copy of the gene