A comparison of collision cross section values obtained via travelling wave ion mobility-mass spectrometry and ultra high performance liquid chromatography-ion mobility-mass spectrometry : application to the characterisation of metabolites in rat urine

A comprehensive Collision Cross Section (CCS) library was obtained via Travelling Wave Ion Guide mobility measurements through direct infusion (DI). The library consists of CCS and Mass Spectral (MS) data in negative and positive ElectroSpray Ionisation (ESI) mode for 463 and 479 endogenous metabolites, respectively. For both ionisation modes combined, TWCCSN2 data were obtained for 542 non-redundant metabolites. These data were acquired on two different ion mobility enabled orthogonal acceleration QToF MS systems in two different laboratories, with the majority of the resulting TWCCSN2 values (from detected compounds) found to be within 1% of one another. Validation of these results against two independent, external TWCCSN2 data sources and predicted TWCCSN2 values indicated to be within 1-2% of these other values. The same metabolites were then analysed using a rapid reversed-phase ultra (high) performance liquid chromatographic (U(H)PLC) separation combined with IM and MS (IM-MS) thus providing retention time (tr), m/z and TWCCSN2 values (with the latter compared with the DI-IM-MS data). Analytes for which TWCCSN2 values were obtained by U(H)PLC-IM-MS showed good agreement with the results obtained from DI-IM-MS. The repeatability of the TWCCSN2 values obtained for these metabolites on the different ion mobility QToF systems, using either DI or LC, encouraged the further evaluation of the U(H)PLC-IM-MS approach via the analysis of samples of rat urine, from control and methotrexate-treated animals, in order to assess the potential of the approach for metabolite identification and profiling in metabolic phenotyping studies. Based on the database derived from the standards 63 metabolites were identified in rat urine, using positive ESI, based on the combination of tr, TWCCSN2 and MS data.</p

IRIS Burst Spectra Co-Spatial To A Quiet-Sun Ellerman-Like Brightening

Ellerman bombs (EBs) have been widely studied over the past two decades; however, only recently have counterparts of these events been observed in the quiet-Sun. The aim of this article is to further understand small-scale quiet-Sun Ellerman-like brightenings (QSEBs) through research into their spectral signatures, including investigating whether the hot signatures associated with some EBs are also visible co-spatial to any QSEBs. We combine H$\alpha$ and Ca II $8542$ \AA\ line scans at the solar limb with spectral and imaging data sampled by the Interface Region Imaging Spectrograph (IRIS). Twenty one QSEBs were identified with average lifetimes, lengths, and widths measured to be around $120$ s, $0.63$", and $0.35$", respectively. Three of these QSEBs displayed clear repetitive flaring through their lifetimes, comparable to the behaviour of EBs in Active Regions (ARs). Two QSEBs in this sample occurred co-spatial with increased emission in SDO/AIA $1600$ \AA\ and IRIS slit-jaw imager $1400$ \AA\ data, however, these intensity increases were smaller than reported co-spatial to EBs. One QSEB was also sampled by the IRIS slit during its lifetime, displaying increases in intensity in the Si IV $1393$ \AA\ and Si IV $1403$ \AA\ cores as well as the C II and Mg II line wings, analogous to IRIS bursts (IBs). Using RADYN simulations, we are unable to reproduce the observed QSEB H$\alpha$ and Ca II $8542$ \AA\ line profiles leaving the question of the temperature stratification of QSEBs open. Our results imply that some QSEBs could be heated to Transition Region temperatures, suggesting that IB profiles should be observed throughout the quiet-Sun

Development and internal validation of a machine learning prediction model for low back pain non-recovery in patients with an acute episode consulting a physiotherapist in primary care

BACKGROUND: While low back pain occurs in nearly everybody and is the leading cause of disability worldwide, we lack instruments to accurately predict persistence of acute low back pain. We aimed to develop and internally validate a machine learning model predicting non-recovery in acute low back pain and to compare this with current practice and 'traditional' prediction modeling. METHODS: Prognostic cohort-study in primary care physiotherapy. Patients (n = 247) with acute low back pain (≤ one month) consulting physiotherapists were included. Candidate predictors were assessed by questionnaire at baseline and (to capture early recovery) after one and two weeks. Primary outcome was non-recovery after three months, defined as at least mild pain (Numeric Rating Scale > 2/10). Machine learning models to predict non-recovery were developed and internally validated, and compared with two current practices in physiotherapy (STarT Back tool and physiotherapists' expectation) and 'traditional' logistic regression analysis. RESULTS: Forty-seven percent of the participants did not recover at three months. The best performing machine learning model showed acceptable predictive performance (area under the curve: 0.66). Although this was no better than a'traditional' logistic regression model, it outperformed current practice. CONCLUSIONS: We developed two prognostic models containing partially different predictors, with acceptable performance for predicting (non-)recovery in patients with acute LBP, which was better than current practice. Our prognostic models have the potential of integration in a clinical decision support system to facilitate data-driven, personalized treatment of acute low back pain, but needs external validation first

280 GHz Focal Plane Unit Design and Characterization for the SPIDER-2 Suborbital Polarimeter

We describe the construction and characterization of the 280 GHz bolometric focal plane units (FPUs) to be deployed on the second flight of the balloon-borne SPIDER instrument. These FPUs are vital to SPIDER's primary science goal of detecting or placing an upper limit on the amplitude of the primordial gravitational wave signature in the cosmic microwave background (CMB) by constraining the B-mode contamination in the CMB from Galactic dust emission. Each 280 GHz focal plane contains a 16 x 16 grid of corrugated silicon feedhorns coupled to an array of aluminum-manganese transition-edge sensor (TES) bolometers fabricated on 150 mm diameter substrates. In total, the three 280 GHz FPUs contain 1,530 polarization sensitive bolometers (765 spatial pixels) optimized for the low loading environment in flight and read out by time-division SQUID multiplexing. In this paper we describe the mechanical, thermal, and magnetic shielding architecture of the focal planes and present cryogenic measurements which characterize yield and the uniformity of several bolometer parameters. The assembled FPUs have high yields, with one array as high as 95% including defects from wiring and readout. We demonstrate high uniformity in device parameters, finding the median saturation power for each TES array to be ~3 pW at 300 mK with a less than 6% variation across each array at one standard deviation. These focal planes will be deployed alongside the 95 and 150 GHz telescopes in the SPIDER-2 instrument, slated to fly from McMurdo Station in Antarctica in December 2018

Design of 280 GHz feedhorn-coupled TES arrays for the balloon-borne polarimeter SPIDER

We describe 280 GHz bolometric detector arrays that instrument the balloon-borne polarimeter SPIDER. A primary science goal of SPIDER is to measure the large-scale B-mode polarization of the cosmic microwave background in search of the cosmic-inflation, gravitational-wave signature. 280 GHz channels aid this science goal by constraining the level of B-mode contamination from galactic dust emission. We present the focal plane unit design, which consists of a 16$\times$16 array of conical, corrugated feedhorns coupled to a monolithic detector array fabricated on a 150 mm diameter silicon wafer. Detector arrays are capable of polarimetric sensing via waveguide probe-coupling to a multiplexed array of transition-edge-sensor (TES) bolometers. The SPIDER receiver has three focal plane units at 280 GHz, which in total contains 765 spatial pixels and 1,530 polarization sensitive bolometers. By fabrication and measurement of single feedhorns, we demonstrate 14.7$^{\circ}$ FHWM Gaussian-shaped beams with $<$1% ellipticity in a 30% fractional bandwidth centered at 280 GHz. We present electromagnetic simulations of the detection circuit, which show 94% band-averaged, single-polarization coupling efficiency, 3% reflection and 3% radiative loss. Lastly, we demonstrate a low thermal conductance bolometer, which is well-described by a simple TES model and exhibits an electrical noise equivalent power (NEP) = 2.6 $\times$ 10$^{-17}$ W/$\sqrt{\mathrm{Hz}}$, consistent with the phonon noise prediction.Comment: Proceedings of SPIE Astronomical Telescopes + Instrumentation 201

Magnetic Flux Cancellation in Ellerman Bombs

Ellerman Bombs (EBs) are often found to be co-spatial with bipolar photospheric magnetic fields. We use Hα imaging spectroscopy along with Fe I 6302.5 Å spectropolarimetry from the Swedish 1 m Solar Telescope (SST), combined with data from the Solar Dynamic Observatory, to study EBs and the evolution of the local magnetic fields at EB locations. EBs are found via an EB detection and tracking algorithm. Using NICOLE inversions of the spectropolarimetric data, we find that, on average, (3.43 ± 0.49) × 1024 erg of stored magnetic energy disappears from the bipolar region during EB burning. The inversions also show flux cancellation rates of 1014–1015 Mx s−1 and temperature enhancements of 200 K at the detection footpoints. We investigate the near-simultaneous flaring of EBs due to co-temporal flux emergence from a sunspot, which shows a decrease in transverse velocity when interacting with an existing, stationary area of opposite polarity magnetic flux, resulting in the formation of the EBs. We also show that these EBs can be fueled further by additional, faster moving, negative magnetic flux regions

Complex chromosome 17p rearrangements associated with low-copy repeats in two patients with congenital anomalies

Recent molecular cytogenetic data have shown that the constitution of complex chromosome rearrangements (CCRs) may be more complicated than previously thought. The complicated nature of these rearrangements challenges the accurate delineation of the chromosomal breakpoints and mechanisms involved. Here, we report a molecular cytogenetic analysis of two patients with congenital anomalies and unbalanced de novo CCRs involving chromosome 17p using high-resolution array-based comparative genomic hybridization (array CGH) and fluorescent in situ hybridization (FISH). In the first patient, a 4-month-old boy with developmental delay, hypotonia, growth retardation, coronal synostosis, mild hypertelorism, and bilateral club feet, we found a duplication of the Charcot-Marie–Tooth disease type 1A and Smith-Magenis syndrome (SMS) chromosome regions, inverted insertion of the Miller-Dieker lissencephaly syndrome region into the SMS region, and two microdeletions including a terminal deletion of 17p. The latter, together with a duplication of 21q22.3-qter detected by array CGH, are likely the unbalanced product of a translocation t(17;21)(p13.3;q22.3). In the second patient, an 8-year-old girl with mental retardation, short stature, microcephaly and mild dysmorphic features, we identified four submicroscopic interspersed 17p duplications. All 17 breakpoints were examined in detail by FISH analysis. We found that four of the breakpoints mapped within known low-copy repeats (LCRs), including LCR17pA, middle SMS-REP/LCR17pB block, and LCR17pC. Our findings suggest that the LCR burden in proximal 17p may have stimulated the formation of these CCRs and, thus, that genome architectural features such as LCRs may have been instrumental in the generation of these CCRs