Platform trials

Platform trials focus on the perpetual testing of many interventions in a disease or a setting. These trials have lasting organizational, administrative, data, analytic, and operational frameworks making them highly efficient. The use of adaptation often increases the probabilities of allocating participants to better interventions and obtaining conclusive results. The COVID-19 pandemic showed the potential of platform trials as a fast and valid way to improved treatments. This review gives an overview of key concepts and elements using the Intensive Care Platform Trial (INCEPT) as an example.</p

Development and validation of a novel risk score for the detection of insignificant prostate cancer in unscreened patient cohorts

Background: Active surveillance is recommended for insignificant prostate cancer (PCa). Tools exist to identify suitable candidates using clinical variables. We aimed to develop and validate a novel risk score (NRS) predicting which patients are harbouring insignificant PCa. / Methods: We used prospectively collected data from 8040 consecutive unscreened patients who underwent radical prostatectomy between 2006 and 2016. Of these, data from 2799 patients with Gleason 3 + 3 on biopsy were used to develop a multivariate model predicting the presence of insignificant PC at radical prostatectomy (ERSPC updated definition3: Gleason 3 + 3 only, index tumour volume < 1.3 cm3 and total tumour volume < 2.5 cm3). This was used to develop a novel risk score (NRS) which was validated in an equivalent independent cohort (n = 441). We compared the accuracy of existing predictive tools and the NRS in these cohorts. / Results: The NRS (incorporating PSA, prostate volume, age, clinical T Stage, percent and number of positive biopsy cores) outperformed pre-existing predictive tools in derivation and validation cohorts (AUC 0.755 and 0.76, respectively). Selection bias due to analysis of a surgical cohort is acknowledged. / Conclusions: The advantage of the NRS is that it can be tailored to patient characteristics and may prove to be valuable tool in clinical decision-making

Comparing working conditions and physical and psychological health complaints in four occupational groups working in female-dominated workplaces

Background Dominant theories of working conditions and their effects on poor employee health have been criticized for failing to consider how psychosocial factors interact and how such relationships may differ across occupational groups. Goal This paper examines the associations between psychosocial factors and physical and psychological health complaints while at the same time taking into account differences between occupational groups in female-dominated professions. Method Four female-dominated occupational groups were included: nurses, health care assistants, cleaners, and dairy industry workers. The relationships between influence, emotional and quantitative demands, social support, back pain, and behavioural stress were examined using structural equation modelling. Results Results supported a group-specific model: the overall pattern remained the same across groups while psychosocial factors had different impacts on poor health and interacted differently across groups. The results also indicated links between psychosocial factors and poor physical health. Conclusion The study confirmed the importance of differentiating between female-dominated occupations rather than talking about women’s working conditions as such. The study also emphasized the importance of considering psychosocial risk factors when examining physical health, in this case back pain

VLTI technical advances: present and future

International audienc

VLTI technical advances: present and future

International audienc

VLTI technical advances: present and future

International audienc

Insights into the phylogeny and coding potential of microbial dark matter

Rinke C, Schwientek P, Sczyrba A, et al. Insights into the phylogeny and coding potential of microbial dark matter. Nature. 2013;499(7459):431-437.Genome sequencing enhances our understanding of the biological world by providing blueprints for the evolutionary and functional diversity that shapes the biosphere. However, microbial genomes that are currently available are of limited phylogenetic breadth, owing to our historical inability to cultivate most microorganisms in the laboratory. We apply single-cell genomics to target and sequence 201 uncultivated archaeal and bacterial cells from nine diverse habitats belonging to 29 major mostly uncharted branches of the tree of life, so-called 'microbial dark matter'. With this additional genomic information, we are able to resolve many intra- and inter-phylum-level relationships and to propose two new superphyla. We uncover unexpected metabolic features that extend our understanding of biology and challenge established boundaries between the three domains of life. These include a novel amino acid use for the opal stop codon, an archaeal-type purine synthesis in Bacteria and complete sigma factors in Archaea similar to those in Bacteria. The single-cell genomes also served to phylogenetically anchor up to 20% of metagenomic reads in some habitats, facilitating organism-level interpretation of ecosystem function. This study greatly expands the genomic representation of the tree of life and provides a systematic step towards a better understanding of biological evolution on our planet