Broadband near-infrared astronomical spectrometer calibration and on-sky validation with an electro-optic laser frequency comb

The quest for extrasolar planets and their characterisation as well as studies of fundamental physics on cosmological scales rely on capabilities of high-resolution astronomical spectroscopy. A central requirement is a precise wavelength calibration of astronomical spectrographs allowing for extraction of subtle wavelength shifts from the spectra of stars and quasars. Here, we present an all-fibre, 400 nm wide near-infrared frequency comb based on electro-optic modulation with 14.5 GHz comb line spacing. Tests on the high-resolution, near-infrared spectrometer GIANO-B show a photon-noise limited calibration precision of <10 cm/s as required for Earth-like planet detection. Moreover, the presented comb provides detailed insight into particularities of the spectrograph such as detector inhomogeneities and differential spectrograph drifts. The system is validated in on-sky observations of a radial velocity standard star (HD221354) and telluric atmospheric absorption features. The advantages of the system include simplicity, robustness and turn-key operation, features that are valuable at the observation sites

Post-Transplant Outcomes in High-Risk Compared with Non-High-Risk Multiple Myeloma: A CIBMTR Analysis.

Conventional cytogenetics and interphase fluorescence in situ hybridization (FISH) identify high-risk multiple myeloma (HRM) populations characterized by poor outcomes. We analyzed these differences among HRM versus non-HRM populations after upfront autologous hematopoietic cell transplantation (autoHCT). Between 2008 and 2012, 715 patients with multiple myeloma identified by FISH and/or cytogenetic data with upfront autoHCT were identified in the Center for International Blood and Marrow Transplant Research database. HRM was defined as del17p, t(4;14), t(14;16), hypodiploidy (-Y) or chromosome 1 p and 1q abnormalities; all others were non-HRM. Among 125 HRM patients (17.5%), induction with bortezomib and immunomodulatory agents (imids) was higher compared with non-HRM (56% versus 43%, P \u3c .001) with similar pretransplant complete response (CR) rates (14% versus 16%, P .1). At day 100 post-transplant, at least a very good partial response was 59% in HRM and 61% in non-HRM (P = .6). More HRM patients received post-transplant therapy with bortezomib and imids (26% versus 12%, P = .004). Three-year post-transplant progression-free (PFS) and overall survival (OS) rates in HRM versus non-HRM were 37% versus 49% (P \u3c .001) and 72% versus 85% (P \u3c .001), respectively. At 3 years, PFS for HRM patients with and without post-transplant therapy was 46% (95% confidence interval [CI], 33 to 59) versus 14% (95% CI, 4 to 29) and in non-HRM patients with and without post-transplant therapy 55% (95% CI, 49 to 62) versus 39% (95% CI, 32 to 47); rates of OS for HRM patients with and without post-transplant therapy were 81% (95% CI, 70 to 90) versus 48% (95% CI, 30 to 65) compared with 88% (95% CI, 84 to 92) and 79% (95% CI, 73 to 85) in non-HRM patients with and without post-transplant therapy, respectively. Among patients receiving post-transplant therapy, there was no difference in OS between HRM and non-HRM (P = .08). In addition to HRM, higher stage, less than a CR pretransplant, lack of post-transplant therapy, and African American race were associated with worse OS. In conclusion, we show HRM patients achieve similar day 100 post-transplant responses compared with non-HRM patients, but these responses are not sustained. Post-transplant therapy appeared to improve the poor outcomes of HRM

Investigation of the grade of calcined clays used as clinker substitute in Limestone Calcined Clay Cement (LC3)

The combination of calcined kaolinitic clays and limestone in Limestone Calcined Clay Cement (LC3) is a promising approach to reduce the cost and the CO2 emissions of cement production by reducing the clinker content of cement. This thesis investigates the feasibility of using various grades of calcined clays in LC3. LC3-50 blends with a clinker content reduced to 50% are studied. The factors controlling the reactivity of LC3-50 blends containing various grades of calcined kaolinitic clays were first studied. A benchmark test of mortar strength was developed. Similar strength to plain Portland cement (PC) can be obtained even for clays with 40% of calcined kaolinite only. Moreover, strengths are strongly dependent on the calcined kaolinite content of the calcined clay. The development of the new Rapid, Relevant and Reliable (R3) pozzolanic test allows the evaluation of the reactivity of calcined clays after only 24 h by isothermal calorimetry and 3 days simply using an oven, and it allows the prediction of the strength development of LC3-50 mortars. To explain strength results, a phase assemblage study was carried out. In order to determine the amount of reacted metakaolin, three methods were tested and mass balance was found to be the most reliable one. The phase assemblage study showed that a critical refinement of pore connectivity is reached already at 3 days for LC3-50 blends with high calcined kaolinite content. From this point on, clinker hydration is slowed down, and the formation of crystalline hydration products is limited. The on-going reaction of metakaolin leads to the higher incorporation of aluminium in the calcium alumino silicate hydrate (C-A-S-H). The C-A-S-H was fully characterized in terms of composition, morphology and density. No change in morphology was observed by Transmission Electron Microscopy. The C-A-S-H density determined by 1H-Nuclear Magnetic Resonance was also found to be similar between PC and LC3-50 with different calcined kaolinite content. Combining all this information, a good relationship is obtained between strength and gel space ratio for PC and for the LC3-50 blends. Finally, the chloride resistance was tested through ponding and chloride binding isotherm tests. The results also support previous findings for the use of calcined clays with a calcined kaolinite content of at least 40% to get a better chloride resistance than PC. These results are mainly explained by the pore connectivity refinement of LC3-50 blends compared with PC. The chloride binding is the highest for clays with 40-50% of calcined kaolinite

Race‐based differences in routine cytogenetic profiles of patients with multiple myeloma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135985/1/bjh13950_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135985/2/bjh13950.pd

Risk and Response-Adapted Treatment in Multiple Myeloma

Myeloma therapeutic strategies have been adapted to patients' age and comorbidities for a long time. However, although cytogenetics and clinical presentations (plasmablastic cytology; extramedullary disease) are major prognostic factors, until recently, all patients received the same treatment whatever their initial risk. No strong evidence allows us to use a personalized treatment according to one cytogenetic abnormality in newly diagnosed myeloma. Retrospective studies showed a benefit of a double autologous transplant in high-risk cytogenetics according to the International Myeloma Working Group definition (t(4;14), t(14;16) or del(17p)). Moreover, this definition has to be updated since other independent abnormalities, namely gain 1q, del(1p32), and trisomies 5 or 21, as well as TP53 mutations, are also prognostic. Another very strong predictive tool is the response to treatment assessed by the evaluation of minimal residual disease (MRD). We are convinced that the time has come to use it to adapt the strategy to a dynamic risk. Many trials are ongoing to answer many questions: when and how should we adapt the therapy, its intensity and duration. Nevertheless, we also have to take into account the clinical outcome for one patient, especially adverse events affecting his or her quality of life and his or her preferences for continuous/fixed duration treatment

Four-color flow cytometry bypasses limitations of IG/TCR polymerase chain reaction for minimal residual disease detection in certain subsets of children with acute lymphoblastic leukemia.

International audienceBACKGROUND AND OBJECTIVES: Competitive immunoglobulin/T-cell receptor polymerase-chain reaction (PCR) analysis with fluorescent detection is a rapid, cheap and reproducible method for quantifying minimal residual disease (MRD), which is well adapted to the recognition of high-risk childhood acute lymphoblastic leukemia (ALL). We aimed at defining whether flow cytometry (FC) techniques can bypass limitations of PCR for MRD determination. DESIGN AND METHODS: We analyzed 140 remission samples from 91 patients using both competitive PCR amplification of antigen-receptor genes and four-color FC identification of leukemia immunophenotype. These methods were chosen with the aim of detecting at least 0.1% blasts. RESULTS: MRD was measured using both PCR and FC methods in 123 samples and the two methods provided concordant results in 119 of them (97%). Moreover, three out of the four discordant results appeared minor since MRD was detectable by both methods, but at different levels. In 12 of 13 samples from nine patients, mainly infants with early CD10- and/or t(4;11) B-cell ALL and children with immature T-cell ALL, MRD could be determined using FC whereas PCR failed. Conversely, FC methods were unfeasible due to inappropriate leukemia immunophenotype in three additional children (including two with T-cell ALL) for whom PCR successfully provided MRD results. INTERPRETATION AND CONCLUSIONS: The MRD results provided by FC techniques were highly concordant with those of competitive PCR. Moreover, the applicability of FC appeared higher in certain ALL subsets, although the appropriateness of this technique in terms of outcome prediction remains to be demonstrated

The shaping and functional consequences of the dosage effect landscape in multiple myeloma

Background: Multiple myeloma (MM) is a malignant proliferation of plasma B cells. Based on recurrent aneuploidy such as copy number alterations (CNAs), myeloma is divided into two subtypes with different CNA patterns and patient survival outcomes. How aneuploidy events arise, and whether they contribute to cancer cell evolution are actively studied. The large amount of transcriptomic changes resultant of CNAs (dosage effect) pose big challenges for identifying functional consequences of CNAs in myeloma in terms of specific driver genes and pathways. In this study, we hypothesize that gene-wise dosage effect varies as a result from complex regulatory networks that translate the impact of CNAs to gene expression, and studying this variation can provide insights into functional effects of CNAs. Results: We propose gene-wise dosage effect score and genome-wide karyotype plot as tools to measure and visualize concordant copy number and expression changes across cancer samples. We find that dosage effect in myeloma is widespread yet variable, and it is correlated with gene expression level and CNA frequencies in different chromosomes. Our analysis suggests that despite the enrichment of differentially expressed genes between hyperdiploid MM and non-hyperdiploid MM in the trisomy chromosomes, the chromosomal proportion of dosage sensitive genes is higher in the non-trisomy chromosomes. Dosage-sensitive genes are enriched by genes with protein translation and localization functions, and dosage resistant genes are enriched by apoptosis genes. These results point to future studies on differential dosage sensitivity and resistance of pro- and anti-proliferation pathways and their variation across patients as therapeutic targets and prognosis markers. Conclusions: Our findings support the hypothesis that recurrent CNAs in myeloma are selected by their functional consequences. The novel dosage effect score defined in this work will facilitate integration of copy number and expression data for identifying driver genes in cancer genomics studies. The accompanying R code is available at http://www.canevolve.org/dosageEffect/