An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles

Objective: New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers. Design: A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles. Results: Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test’s ability to discriminate between CRC and non-cancer states (phase I), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations (phase II). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence. Conclusion: New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact

RNA-Seq comparative study reveals molecular effectors linked to the resistance of Pinna nobilis to Haplosporidium pinnae parasite

International audienceAbstract With the intensification of maritime traffic, recently emerged infectious diseases have become major drivers in the decline and extinction of species. Since 2016, mass mortality events have decimated the endemic Mediterranean Sea bivalve Pinna nobilis, affecting ca. 100% of individuals. These events have largely been driven by Haplosporidium pinnae ’s infection, an invasive species which was likely introduced by shipping. While monitoring wild populations of P. nobilis , we observed individuals that survived such a mass mortality event during the summer of 2018 (France). We considered these individuals resistant, as they did not show any symptoms of the disease, while the rest of the population in the area was devastated. Furthermore, the parasite was not detected when we conducted a PCR amplification of a species-specific fragment of the small subunit ribosomal DNA. In parallel, the transcriptomic analysis showed evidence of some parasite RNA indicating that the resistant individuals had been exposed to the parasite without proliferating. To understand the underlying mechanisms of resistance in these individuals, we compared their gene expression with that of susceptible individuals. We performed de novo transcriptome assembly and annotated the expressed genes. A comparison of the transcriptomes in resistant and susceptible individuals highlighted a gene expression signature of the resistant phenotype. We found significant differential expressions of genes involved in immunity and cell architecture. This data provides the first insights into how individuals escape the pathogenicity associated with infection

MURMUR: a new low-noise experiment for the search of neutron-hidden neutron transitions in the context of braneworld scenarios

International audience{MURMUR is a new passing-through-walls neutron experiment installed near the BR2 nuclear reactor at the Belgian Nuclear Research Center (SCK$\cdot$CEN, Mol, Belgium) and designed to search neutron interbrane transitions in the context of braneworld scenarios. In such scenarios, our visible Universe could be a 3-brane embedded in a multidimensional space-time, called the bulk, which could contain some other invisible adjacent 3-branes. Theoretical works have shown that the existence of hidden braneworlds can be experimentally tested thanks to neutron exchanges between braneworlds. A neutron $n$ in our visible brane can be converted into a hidden neutron $n'$ -- propagating in a hidden braneworld -- when scattered by a nucleus with a cross section $\sigma \big( n \rightarrow n'\big) \sim \sigma_E \big(n \rightarrow n \big) \times p$, where $\sigma_E$ is the usual elastic cross-section and $p$ the neutron swapping probability. Hidden neutrons could thus be generated in the moderator of the BR2 nuclear reactor where a high neutron flux undergoes many elastic scatterings. This hidden neutron flux could be free to travel out of the biological shielding of the reactor up to a matrix made of lead, acting as an antenna, which makes possible to regenerate hidden neutrons into visible ones thanks to reverse swapping. These regenerated neutrons can be detected thanks to a neutron detector placed inside the lead block. The MURMUR experimental setup is described, as well as the included upgrades compared to the first experiment of this kind carried out at the ILL (Grenoble, France) in 2015. The first results of MURMUR are introduced and discussed, and some upcoming improvements of the experimental setup are introduced

Detection of Alzheimer's disease signature in MR images seven years before conversion to dementia: Toward an early individual prognosis.

International audienceFinding very early biomarkers of Alzheimer’s Disease (AD) to aid in individual prognosis is of major interest to accelerate the development of new therapies. Among the potential biomarkers, neurodegeneration measurements from MRI are considered as good candidates but have so far not been effective at the early stages of the pathology. Our objective is to investigate the efficiency of a new MR-based hippocampal grading score to detect incident dementia in cognitively intact patients. This new score is based on a pattern recognition strategy, providing a grading measure that reflects the similarity of the anatomical patterns of the subject under study with dataset composed of healthy subjects and patients with AD. Hippocampal grading was evaluated on subjects from the Three-City cohort, with a follow-up period of 12 years. Experiments demonstrate that hippocampal grading yields prediction accuracy up to 72.5% (p<0.0001) 7 years before conversion to AD, better than both hippocampal volume (58.1%, p=0.04) and MMSE score (56.9%, p=0.08). The area under the ROC curve (AUC) supports the efficiency of imaging biomarkers with a gain of 8.4 percentage points for hippocampal grade (73.0%) over hippocampal volume (64.6%). Adaptation of the proposed framework to clinical score estimation is also presented. Compared to previous studies investigating new biomarkers for AD prediction over much shorter periods, the very long follow-up of the Three-City cohort demonstrates the important clinical potential of the proposed imaging biomarker. The high accuracy obtained with this new imaging biomarker paves the way for computer-based prognostic aides to help the clinician identify cognitively intact subjects that are at high risk to develop AD