X-ray multilayer monochromator with enhanced performance

International audienceAn x-ray multilayer monochromator with improved resolution and a low specular background is presented. The monochromator consists of a lamellar multilayer amplitude grating with appropriate parameters used at the zeroth diffraction order. The device is fabricated by means of combining deposition of thin films on a nanometer scale, UV lithography, and reactive ion etching. The performance of this new monochromator at photon energies near 1500 eV is shown

Fusion transcripts and their genomic breakpoints in polyadenylated and ribosomal RNA-minus RNA sequencing data

BACKGROUND: Fusion genes are typically identified by RNA sequencing (RNA-seq) without elucidating the causal genomic breakpoints. However, non–poly(A)-enriched RNA-seq contains large proportions of intronic reads that also span genomic breakpoints. RESULTS: We have developed an algorithm, Dr. Disco, that searches for fusion transcripts by taking an entire reference genome into account as search space. This includes exons but also introns, intergenic regions, and sequences that do not meet splice junction motifs. Using 1,275 RNA-seq samples, we investigated to what extent genomic breakpoints can be extracted from RNA-seq data and their implications regarding poly(A)-enriched and ribosomal RNA–minus RNA-seq data. Comparison with whole-genome sequencing data revealed that most genomic breakpoints are not, or minimally, transcribed while, in contrast, the genomic breakpoints of all 32 TMPRSS2-ERG–positive tumours were present at RNA level. We also revealed tumours in which the ERG breakpoint was located before ERG, which co-existed with additional deletions and messenger RNA that incorporated intergenic cryptic exons. In breast cancer we identified rearrangement hot spots near CCND1 and in glioma near CDK4 and MDM2 and could directly associate this with increased expression. Furthermore, in all datasets we find fusions to intergenic regions, often spanning multiple cryptic exons that potentially encode neo-antigens. Thus, fusion transcripts other than classical gene-to-gene fusions are prominently present and can be identified using RNA-seq. CONCLUSION: By using the full potential of non–poly(A)-enriched RNA-seq data, sophisticated analysis can reliably identify expressed genomic breakpoints and their transcriptional effects

Consensus molecular subtype classification of colorectal adenomas

Consensus molecular subtyping is an RNA expression-based classification system for colorectal cancer (CRC). Genomic alterations accumulate during CRC pathogenesis, including the premalignant adenoma stage, leading to changes in RNA expression. Only a minority of adenomas progress to malignancies, a transition that is associated with specific DNA copy number aberrations or microsatellite instability (MSI). We aimed to investigate whether colorectal adenomas can already be stratified into consensus molecular subtype (CMS) classes, and whether specific CMS classes are related to the presence of specific DNA copy number aberrations associated with progression to malignancy. RNA sequencing was performed on 62 adenomas and 59 CRCs. MSI status was determined with polymerase chain reaction-based methodology. DNA copy number was assessed by low-coverage DNA sequencing (n = 30) or array-comparative genomic hybridisation (n = 32). Adenomas were classified into CMS classes together with CRCs from the study cohort and from The Cancer Genome Atlas (n = 556), by use of the established CMS classifier. As a result, 54 of 62 (87%) adenomas were classified according to the CMS. The CMS3 ‘metabolic subtype’, which was least common among CRCs, was most prevalent among adenomas (n = 45; 73%). One of the two adenomas showing MSI was classified as CMS1 (2%), the ‘MSI immune’ subtype. Eight adenomas (13%) were classified as the ‘canonical’ CMS2. No adenomas were classified as the ‘mesenchymal’ CMS4, consistent with the fact that adenomas lack invasion-associated stroma. The distribution of the CMS classes among adenomas was confirmed in an independent series. CMS3 was enriched with adenomas at low risk of progressing to CRC, whereas relatively more high-risk adenomas were observed in CMS2. We conclude that adenomas can be stratified into the CMS classes. Considering that CMS1 and CMS2 expression signatures may mark adenomas at increased risk of progression, the distribution of the CMS classes among adenomas is consistent with the proportion of adenomas expected to progress to CRC

Étude de la transformation d'une titanomagnétite en titanomaghémite dans une roche volcanique

This study is concerned with a crystal of titanomagnetite the margin of which is mainly transformed into titanomaghemite. The dispersion curves of reflectivity which were drawn for the two parts of this cristal are compared to those of known minerals. Electron microprobe analysis shows that the amount of iron decreases while titanium and manganese increase on the margin of the crystal. Thus the maghemitization of such a natural titanomagnetite is not just a simple oxidation process. The diffusion of some cations (titanium and manganese in this case) results in a partial occupation of theoretically vacant positions in the crystal structure. The increase in the number of atoms of titanium and manganese influences the amount of iron which does not depend only on the degree of oxidation of the mineral. Consequently, the magnetic properties of titanomaghemites should be different from those deduced theoretically.Cette étude porte sur un cristal de titanomagnétite largement transformé sur sa bordure en titanomaghémite. Les courbes de dispersion des pouvoirs réflecteurs des deux plages correspondantes sont comparées à celles de minéraux connus. L'analyse à la microsonde électronique met en évidence une forte diminution de la teneur en fer et une augmentation importante pour celles du titane et du manganèse dans la bordure du cristal. L'interprétation de ces résultats conduit à penser que la maghémitisation de la titanomagnétite correspond non seulement à une oxydation du fer mais encore à une diffusion de cations qui viennent occuper partiellement les sites cristallographiques théoriquement vacants ; l'enrichissement en titane et en manganèse influe sur la teneur en fer qui ne dépend pas uniquement du degré d'oxydation du minéral. Les propriétés magnétiques des titanomaghémites devraient donc être différentes de celles prévues par la théorie.Prévôt M., Remond Guy, Caye René. Étude de la transformation d'une titanomagnétite en titanomaghémite dans une roche volcanique. In: Bulletin de la Société française de Minéralogie et de Cristallographie, volume 91, 1, 1968. pp. 65-74

L’efficience nette de conversion des aliments par les animaux d’élevage : une nouvelle approche pour évaluer la contribution de l’élevage à l’alimentation humaine

Dossier : ressources alimentaires pour les animaux d'élevageL’efficience nette de conversion des aliments par les animaux d’élevage : une nouvelle approche pour évaluer la contribution de l’élevage à l’alimentation humain

Clinical Validation of a Multitarget Fecal Immunochemical Test for Colorectal Cancer Screening: A Diagnostic Test Accuracy Study

Background: The fecal immunochemical test (FIT) is used in colorectal cancer (CRC) screening, yet it leaves room for improvement. Objective: To develop a multitarget FIT (mtFIT) with better diagnostic performance than FIT. Design: Diagnostic test accuracy study. Setting: Colonoscopy-controlled series. Participants: Persons (n = 1284) from a screening (n = 1038) and referral (n = 246) population were classified by their most advanced lesion (CRC [n = 47], advanced adenoma [n = 135], advanced serrated polyp [n = 30], nonadvanced adenoma [n = 250], and nonadvanced serrated polyp [n = 53]), along with control participants (n = 769). Measurements: Antibody-based assays were developed and applied to leftover FIT material. Classification and regression tree (CART) analysis was applied to biomarker concentrations to identify the optimal combination for detecting advanced neoplasia. Performance of this combination, the mtFIT, was cross-validated using a leave-one-out approach and compared with FIT at equal specificity. Results: The CART analysis showed a combination of hemoglobin, calprotectin, and serpin family F member 2-the mtFIT-to have a cross-validated sensitivity for advanced neoplasia of 42.9% (95% CI, 36.2% to 49.9%) versus 37.3% (CI, 30.7% to 44.2%) for FIT (P = 0.025), with equal specificity of 96.6%. In particular, cross-validated sensitivity for advanced adenomas increased from 28.1% (CI, 20.8% to 36.5%) to 37.8% (CI, 29.6% to 46.5%) (P = 0.006). On the basis of these results, early health technology assessment indicated that mtFIT-based screening could be cost-effective compared with FIT. Limitation: Study population is enriched with persons from a referral population. Conclusion: Compared with FIT, the mtFIT showed better diagnostic accuracy in detecting advanced neoplasia because of an increased detection of advanced adenomas. Moreover, early health technology assessment indicated that these results provide a sound basis to pursue further development of mtFIT as a future test for populationbased CRC screening. A prospective screening trial is in preparation

First-line palliative systemic therapy alternated with oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy for unresectable colorectal peritoneal metastases: A single-arm phase II trial (CRC-PIPAC-II)

Background: Palliative systemic therapy alternated with electrostatic precipitation oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (ePIPAC) has never been prospectively investigated in patients with unresectable colorectal peritoneal metastases (CPM). The CRC-PIPAC-II study aimed to assess safety, feasibility and efficacy of such bidirectional therapy. Methods: This two-center, single-arm, phase II trial enrolled chemotherapy-naïve patients to undergo three treatment cycles, consisting of systemic therapy (CAPOX, FOLFOX, FOLFIRI, or FOLFOXIRI, all with bevacizumab) and oxaliplatin-based ePIPAC (92 mg/m2) with intravenous leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2). Primary outcome were major treatment-related adverse events. Secondary outcomes included minor events, tumor response, progression-free survival (PFS) and overall survival (OS). Results: Twenty patients completed 52 treatment cycles. Fifteen major events occurred in 7 patients (35 %): 5 events (33 %) related to systemic therapy; 5 (33 %) related to ePIPAC; and 5 (33 %) were biochemical events. No treatment-related deaths occurred. All patients experienced minor events, mostly abdominal pain, nausea and peripheral sensory neuropathy. After treatment, radiological, pathological, cytological, and biochemical response was observed in 0 %, 88 %, 38 %, and 31 % of patients respectively. Curative surgery was achieved in one patient. Median PFS was 10.0 months (95 % confidence interval [CI] 8.0–13.0) and median OS was 17.5 months (95 % CI 13.0–not reached). Conclusions: Combining palliative systemic therapy with oxaliplatin-based ePIPAC in patients with unresectable CPM was feasible and showed an acceptable safety profile. Treatment-induced response and survival are promising, yet further research is required to determine the additional value of ePIPAC to systemic therapy