Arcanobacterium haemolyticum associated with pyothorax: case report

Arcanobacterium haemolyticum has an established role in the etiology of human pharyngitis. There are increasing reports of systemic infections caused by this organism. From India, we report the first case of Arcanobacterium haemolyticum causing pyothorax in an immunocompetent adolescent male patient. The probable mode of infection is also discussed. The role of A. hemolyticum as an animal pathogen needs further study

A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS)

This randomized, phase III, open-label, multicenter study compared carfilzomib monotherapy against low-dose corticosteroids and optional cyclophosphamide in relapsed and refractory multiple myeloma (RRMM). Relapsed and refractory multiple myeloma patients were randomized (1:1) to receive carfilzomib (10-min intravenous infusion; 20 mg/m(2) on days 1 and 2 of cycle 1; 27 mg/m(2) thereafter) or a control regimen of low-dose corticosteroids (84 mg of dexamethasone or equivalent corticosteroid) with optional cyclophosphamide (1400 mg) for 28-day cycles. The primary endpoint was overall survival (OS). Three-hundred and fifteen patients were randomized to carfilzomib (n=157) or control (n=158). Both groups had a median of five prior regimens. In the control group, 95% of patients received cyclophosphamide. Median OS was 10.2 (95% confidence interval (CI) 8.4-14.4) vs 10.0 months (95% CI 7.7-12.0) with carfilzomib vs control (hazard ratio=0.975; 95% CI 0.760-1.249; P=0.4172). Progression-free survival was similar between groups; overall response rate was higher with carfilzomib (19.1 vs 11.4%). The most common grade ⩾3 adverse events were anemia (25.5 vs 30.7%), thrombocytopenia (24.2 vs 22.2%) and neutropenia (7.6 vs 12.4%) with carfilzomib vs control. Median OS for single-agent carfilzomib was similar to that for an active doublet control regimen in heavily pretreated RRMM patients

Neoproterozoic iron formation: An evaluation of its temporal, environmental and tectonic significance

Neoproterozoic iron formation (NIF) provides evidence for the widespread return of anoxic and ferruginous basins during a time period associated with major changes in climate, tectonics and biogeochemistry of the oceans. Here we summarize the stratigraphic context of Neoproterozoic iron formation and its geographic and temporal distribution. It is evident that most NIF is associated with the earlier Cryogenian (Sturtian) glacial epoch. Although it is possible that some NIF may be Ediacaran, there is no incontrovertible evidence to support this age assignment. The paleogeographic distribution of NIF is consistent with anoxic and ferruginous conditions occurring in basins within Rodinia or in rift-basins developed on its margins. Consequently NIF does not require whole ocean anoxia. Simple calculations using modern day iron fluxes suggest that only models that invoke hydrothermal and/or detrital sources of iron are capable of supplying sufficient iron to account for the mass of the larger NIF occurrences. This conclusion is reinforced by the available geochemical data that imply NIF record is a mixture of hydrothermal and detrital components. A common thread that appears to link most if not all NIF is an association with mafic volcanics.Earth and Planetary Science

Ascomycetous yeast species recovered from grapes damaged by honeydew and sour rot

Aims: To identify ascomycetous yeasts recovered from sound and damaged grapes by the presence of honeydew or sour rot. Methods and Results: In sound grapes, the mean yeast counts ranged from 3.20 ± 1.04 log CFU g-1 to 5.87 ± 0.64 log CFU g-1. In honeydew grapes, the mean counts ranged from 3.88 ± 0.80 log CFU g-1 to 6.64 ± 0.77 log CFU g-1. In sour rot grapes counts varied between 6.34 ± 1.03 and 7.68 ± 0.38 log CFU g-1. Hanseniaspora uvarum was the most frequent species from sound samples. In both types of damage, the most frequent species were Candida vanderwaltii, H. uvarum and Zygoascus hellenicus. The latter species was recovered in high frequency because of the utilization of the selective medium DBDM (Dekkera ⁄ Brettanomyces differential medium). The scarce isolation frequency of the wine spoilage species Zygosaccharomyces bailii (in sour rotten grapes) and Zygosaccharomyces bisporus (in honeydew affected grapes) could only be demonstrated by the use of the selective medium ZDM (Zygosaccharomyces differential medium). Conclusions: The isolation of several species only from damaged grapes indicates that damage constituted the main factor determining yeast diversity. The utilization of selective media is required for eliciting the recovery of potentially wine spoilage species. Significance and Impact of the Study: The impact of damaged grapes in the yeast ecology of grapes has been underestimate

Utilization of Benchtop Next Generation Sequencing Platforms Ion Torrent PGM and MiSeq in Noninvasive Prenatal Testing for Chromosome 21 Trisomy and Testing of Impact of In Silico and Physical Size Selection on Its Analytical Performance

OBJECTIVES: The aims of this study were to test the utility of benchtop NGS platforms for NIPT for trisomy 21 using previously published z score calculation methods and to optimize the sample preparation and data analysis with use of in silico and physical size selection methods. METHODS: Samples from 130 pregnant women were analyzed by whole genome sequencing on benchtop NGS systems Ion Torrent PGM and MiSeq. The targeted yield of 3 million raw reads on each platform was used for z score calculation. The impact of in silico and physical size selection on analytical performance of the test was studied. RESULTS: Using a z score value of 3 as the cut-off, 98.11% - 100% (104-106/106) specificity and 100% (24/24) sensitivity and 99.06% - 100% (105-106/106) specificity and 100% (24/24) sensitivity were observed for Ion Torrent PGM and MiSeq, respectively. After in silico based size selection both platforms reached 100% specificity and sensitivity. Following the physical size selection z scores of tested trisomic samples increased significantly-p = 0.0141 and p = 0.025 for Ion Torrent PGM and MiSeq, respectively. CONCLUSIONS: Noninvasive prenatal testing for chromosome 21 trisomy with the utilization of benchtop NGS systems led to results equivalent to previously published studies performed on high-to-ultrahigh throughput NGS systems. The in silico size selection led to higher specificity of the test. Physical size selection performed on isolated DNA led to significant increase in z scores. The observed results could represent a basis for increasing of cost effectiveness of the test and thus help with its penetration worldwide

Personalised progression prediction in patients with monoclonal gammopathy of undetermined significance or smouldering multiple myeloma (PANGEA): a retrospective, multicohort study

BACKGROUND: Patients with precursors to multiple myeloma are dichotomised as having monoclonal gammopathy of undetermined significance or smouldering multiple myeloma on the basis of monoclonal protein concentrations or bone marrow plasma cell percentage. Current risk stratifications use laboratory measurements at diagnosis and do not incorporate time-varying biomarkers. Our goal was to develop a monoclonal gammopathy of undetermined significance and smouldering multiple myeloma stratification algorithm that utilised accessible, time-varying biomarkers to model risk of progression to multiple myeloma. METHODS: In this retrospective, multicohort study, we included patients who were 18 years or older with monoclonal gammopathy of undetermined significance or smouldering multiple myeloma. We evaluated several modelling approaches for predicting disease progression to multiple myeloma using a training cohort (with patients at Dana-Farber Cancer Institute, Boston, MA, USA; annotated from Nov, 13, 2019, to April, 13, 2022). We created the PANGEA models, which used data on biomarkers (monoclonal protein concentration, free light chain ratio, age, creatinine concentration, and bone marrow plasma cell percentage) and haemoglobin trajectories from medical records to predict progression from precursor disease to multiple myeloma. The models were validated in two independent validation cohorts from National and Kapodistrian University of Athens (Athens, Greece; from Jan 26, 2020, to Feb 7, 2022; validation cohort 1), University College London (London, UK; from June 9, 2020, to April 10, 2022; validation cohort 1), and Registry of Monoclonal Gammopathies (Czech Republic, Czech Republic; Jan 5, 2004, to March 10, 2022; validation cohort 2). We compared the PANGEA models (with bone marrow [BM] data and without bone marrow [no BM] data) to current criteria (International Myeloma Working Group [IMWG] monoclonal gammopathy of undetermined significance and 20/2/20 smouldering multiple myeloma risk criteria). FINDINGS: We included 6441 patients, 4931 (77%) with monoclonal gammopathy of undetermined significance and 1510 (23%) with smouldering multiple myeloma. 3430 (53%) of 6441 participants were female. The PANGEA model (BM) improved prediction of progression from smouldering multiple myeloma to multiple myeloma compared with the 20/2/20 model, with a C-statistic increase from 0·533 (0·480-0·709) to 0·756 (0·629-0·785) at patient visit 1 to the clinic, 0·613 (0·504-0·704) to 0·720 (0·592-0·775) at visit 2, and 0·637 (0·386-0·841) to 0·756 (0·547-0·830) at visit three in validation cohort 1. The PANGEA model (no BM) improved prediction of smouldering multiple myeloma progression to multiple myeloma compared with the 20/2/20 model with a C-statistic increase from 0·534 (0·501-0·672) to 0·692 (0·614-0·736) at visit 1, 0·573 (0·518-0·647) to 0·693 (0·605-0·734) at visit 2, and 0·560 (0·497-0·645) to 0·692 (0·570-0·708) at visit 3 in validation cohort 1. The PANGEA models improved prediction of monoclonal gammopathy of undetermined significance progression to multiple myeloma compared with the IMWG rolling model at visit 1 in validation cohort 2, with C-statistics increases from 0·640 (0·518-0·718) to 0·729 (0·643-0·941) for the PANGEA model (BM) and 0·670 (0·523-0·729) to 0·879 (0·586-0·938) for the PANGEA model (no BM). INTERPRETATION: Use of the PANGEA models in clinical practice will allow patients with precursor disease to receive more accurate measures of their risk of progression to multiple myeloma, thus prompting for more appropriate treatment strategies. FUNDING: SU2C Dream Team and Cancer Research UK

Electrical conductivity during incipient melting in the oceanic low-velocity zone

International audienceThe low-viscosity layer in the upper mantle, the asthenosphere, is a requirement for plate tectonics1. The seismic low velocities and the high electrical conductivities of the asthenosphere are attributed either to subsolidus, water-related defects in olivine minerals2, 3, 4 or to a few volume per cent of partial melt5, 6, 7, 8, but these two interpretations have two shortcomings. First, the amount of water stored in olivine is not expected to be higher than 50 parts per million owing to partitioning with other mantle phases9 (including pargasite amphibole at moderate temperatures10) and partial melting at high temperatures9. Second, elevated melt volume fractions are impeded by the temperatures prevailing in the asthenosphere, which are too low, and by the melt mobility, which is high and can lead to gravitational segregation11, 12. Here we determine the electrical conductivity of carbon-dioxide-rich and water-rich melts, typically produced at the onset of mantle melting. Electrical conductivity increases modestly with moderate amounts of water and carbon dioxide, but it increases drastically once the carbon dioxide content exceeds six weight per cent in the melt. Incipient melts, long-expected to prevail in the asthenosphere10, 13, 14, 15, can therefore produce high electrical conductivities there. Taking into account variable degrees of depletion of the mantle in water and carbon dioxide, and their effect on the petrology of incipient melting, we calculated conductivity profiles across the asthenosphere for various tectonic plate ages. Several electrical discontinuities are predicted and match geophysical observations in a consistent petrological and geochemical framework. In moderately aged plates (more than five million years old), incipient melts probably trigger both the seismic low velocities and the high electrical conductivities in the upper part of the asthenosphere, whereas in young plates4, where seamount volcanism occurs6, a higher degree of melting is expected

Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats

Peer reviewe

Abdo-Man: a 3D-printed anthropomorphic phantom for validating quantitative SIRT

BACKGROUND: The use of selective internal radiation therapy (SIRT) is rapidly increasing, and the need for quantification and dosimetry is becoming more widespread to facilitate treatment planning and verification. The aim of this project was to develop an anthropomorphic phantom that can be used as a validation tool for post-SIRT imaging and its application to dosimetry. METHOD: The phantom design was based on anatomical data obtained from a T1-weighted volume-interpolated breath-hold examination (VIBE) on a Siemens Aera 1.5 T MRI scanner. The liver, lungs and abdominal trunk were segmented using the Hermes image processing workstation. Organ volumes were then uploaded to the Delft Visualization and Image processing Development Environment for smoothing and surface rendering. Triangular meshes defining the iso-surfaces were saved as stereo lithography (STL) files and imported into the Autodesk® Meshmixer software. Organ volumes were subtracted from the abdomen and a removable base designed to allow access to the liver cavity. Connection points for placing lesion inserts and filling holes were also included. The phantom was manufactured using a Stratasys Connex3 PolyJet 3D printer. The printer uses stereolithography technology combined with ink jet printing. Print material is a solid acrylic plastic, with similar properties to polymethylmethacrylate (PMMA). RESULTS: Measured Hounsfield units and calculated attenuation coefficients of the material were shown to also be similar to PMMA. Total print time for the phantom was approximately 5 days. Initial scans of the phantom have been performed with Y-90 bremsstrahlung SPECT/CT, Y-90 PET/CT and Tc-99m SPECT/CT. The CT component of these images compared well with the original anatomical reference, and measurements of volume agreed to within 9 %. Quantitative analysis of the phantom was performed using all three imaging techniques. Lesion and normal liver absorbed doses were calculated from the quantitative images in three dimensions using the local deposition method. CONCLUSIONS: 3D printing is a flexible and cost-efficient technology for manufacture of anthropomorphic phantom. Application of such phantoms will enable quantitative imaging and dosimetry methodologies to be evaluated, which with optimisation could help improve outcome for patients