Novel approaches to the synthesis of aromatic compounds

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Development and initial testing of valves opened by Valsalva (abdominal straining):Proof of principle for urinary catheters or male urethra

We hypothesised that raising the abdominal pressure could provide a non-manual approach to opening a urinary valve, with potential application for indwelling catheters or an intraurethral device. The ‘Vysera’ valve remains closed during short high amplitude spikes but opens when a pre-defined low-amplitude pressure is maintained for a pre-specified duration, allowing sustained abdominal straining to achieve voluntary opening. The valve was subjected to in vitro performance and microbiological tests. Parameters for valve specification were selected by review of a large urodynamic database with nominal opening pressure of 75 cmH2O +/-15 cmH2O (range 60-90 cmH2O) and valve pressure was refined using early clinical results. Valve housings were designed for the end of a Foley catheter, and for male post-prostatectomy intraurethral placement. Preliminary clinical evaluation was undertaken for both designs, incorporating qualitative feedback. In vitro testing of the catheter valve demonstrated only minimal encrustation. On clinical evaluation of the catheter-sited value, six of seven patients (86%) were able to open the valve intentionally by straining. When inactive, none of the patients experienced leakage (7/7=100%), while five (71%) leaked when they coughed. The intraurethral device was successfully placed with image intensifier guidance under general anaesthetic in five of nine patients. Three patients used the device; initial leakage resolved as patients mobilised. However, in contrast to the catheter-sited valve, the intraurethral device was difficult to tolerate for even a few hours. Removal was performed under local anaesthesia with a flexible cystoscope and stent grasper. We conclude that storage and bladder emptying using a strain-activated valve are feasible for a catheter valve and an intra-urethral device. The valve parameters need to be matched to individual patients. For the intraurethral device, additional development is needed to improve the stent housing and valve performance

Fast and low loss flexoelectro-optic liquid crystal phase modulator with a chiral nematic reflector.

In this paper, we demonstrate a flexoelectro-optic liquid crystal phase-only device that uses a chiral nematic reflector to achieve full 2π phase modulation. This configuration is found to be very tolerant to imperfections in the chiral nematic reflector provided that the flexoelectro-optic LC layer fulfils the half-wave condition. Encouragingly, the modulation in the phase, which operates at kHz frame rates, is also accompanied by low amplitude modulation. The configuration demonstrated herein is particularly promising for the development of next-generation liquid crystal on silicon spatial light modulators

Proton conduction in a phosphonate-based metal-organic framework mediated by intrinsic “free diffusion inside a sphere”

Understanding the molecular mechanism of proton conduction is crucial for the design of new materials with improved conductivity. Quasi-elastic neutron scattering (QENS) has been used to probe the mechanism of proton diffusion within a new phosphonate-based metal–organic framework (MOF) material, MFM-500(Ni). QENS suggests that the proton conductivity (4.5 × 10–4 S/cm at 98% relative humidity and 25 °C) of MFM-500(Ni) is mediated by intrinsic “free diffusion inside a sphere”, representing the first example of such a mechanism observed in MOFs

Transancestral mapping of the MHC region in systemic lupus erythematosus identifies new independent and interacting loci at MSH5, HLA-DPB1 and HLA-G

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic multisystem genetically complex autoimmune disease characterised by the production of autoantibodies to nuclear and cellular antigens, tissue inflammation and organ damage. Genome-wide association studies have shown that variants within the major histocompatibility complex (MHC) region on chromosome 6 confer the greatest genetic risk for SLE in European and Chinese populations. However, the causal variants remain elusive due to tight linkage disequilibrium across disease-associated MHC haplotypes, the highly polymorphic nature of many MHC genes and the heterogeneity of the SLE phenotype. METHODS: A high-density case-control single nucleotide polymorphism (SNP) study of the MHC region was undertaken in SLE cohorts of Spanish and Filipino ancestry using a custom Illumina chip in order to fine-map association signals in these haplotypically diverse populations. In addition, comparative analyses were performed between these two datasets and a northern European UK SLE cohort. A total of 1433 cases and 1458 matched controls were examined. RESULTS: Using this transancestral SNP mapping approach, novel independent loci were identified within the MHC region in UK, Spanish and Filipino patients with SLE with some evidence of interaction. These loci include HLA-DPB1, HLA-G and MSH5 which are independent of each other and HLA-DRB1 alleles. Furthermore, the established SLE-associated HLA-DRB1*15 signal was refined to an interval encompassing HLA-DRB1 and HLA-DQA1. Increased frequencies of MHC region risk alleles and haplotypes were found in the Filipino population compared with Europeans, suggesting that the greater disease burden in non-European SLE may be due in part to this phenomenon. CONCLUSION: These data highlight the usefulness of mapping disease susceptibility loci using a transancestral approach, particularly in a region as complex as the MHC, and offer a springboard for further fine-mapping, resequencing and transcriptomic analysis

Feasibility of non-invasive neuro-monitoring during extracorporeal membrane oxygenation in children

Introduction Detection of neurological complications during extracorporeal membrane oxygenation (ECMO) may be enhanced with non-invasive neuro-monitoring. We investigated the feasibility of non-invasive neuro-monitoring in a paediatric intensive care (PIC) setting. Methods In a single centre, prospective cohort study we assessed feasibility of recruitment, and neuro-monitoring via somatosensory evoked potentials (SSEP), electroencephalography (EEG) and near infrared spectroscopy (NIRS) during venoarterial (VA) ECMO in paediatric patients (0–15 years). Measures were obtained within 24h of cannulation, during an intermediate period, and finally at decannulation or echo stress testing. SSEP/EEG/NIRS measures were correlated with neuro-radiology findings, and clinical outcome assessed via the Pediatric cerebral performance category (PCPC) scale 30 days post ECMO cannulation. Results We recruited 14/20 (70%) eligible patients (median age: 9 months; IQR:4–54, 57% male) over an 18-month period, resulting in a total of 42 possible SSEP/EEG/NIRS measurements. Of these, 32/42 (76%) were completed. Missed recordings were due to lack of access/consent within 24 h of cannulation (5/42, 12%) or PIC death/discharge (5/42, 12%). In each patient, the majority of SSEP (8/14, 57%), EEG (8/14, 57%) and NIRS (11/14, 79%) test results were within normal limits. All patients with abnormal neuroradiology (4/10, 40%), and 6/7 (86%) with poor outcome (PCPC ≥4) developed indirect SSEP, EEG or NIRS measures of neurological complications prior to decannulation. No study-related adverse events or neuro-monitoring data interpreting issues were experienced. Conclusion Non-invasive neuro-monitoring (SSEP/EEG/NIRS) during ECMO is feasible and may provide early indication of neurological complications in this high-risk population

On-sky results for the integrated microlens ring tip-tilt sensor

We present the first on-sky results of the microlens ring tip-tilt sensor. This sensor uses a 3D printed microlens ring feeding six multimode fibers to sense misaligned light, allowing centroid reconstruction. A tip-tilt mirror allows the beam to be corrected, increasing the amount of light coupled into a centrally positioned single-mode (science) fiber. The sensor was tested with the iLocater acquisition camera at the Large Binocular Telescope in Tucson, Arizona, in November 2019. The limit on the maximum achieved rms reconstruction accuracy was found to be 0.19/D in both tip and tilt, of which approximately 50% of the power originates at frequencies below 10 Hz. We show the reconstruction accuracy is highly dependent on the estimated Strehl ratio and simulations support the assumption that residual adaptive optics aberrations are the main limit to the reconstruction accuracy. We conclude that this sensor is ideally suited to remove post-adaptive optics noncommon path tip-tilt residuals. We discuss the next steps for concept development, including optimization of the lens and the fiber, tuning of the correction algorithm, and selection of optimal science cases

Groundwater dynamics in coastal gravel barriers backed by freshwater lagoons and the potential for saline intrusion: Two cases from the UK

“NOTICE: this is the author’s version of a work that was accepted for publication in Journal of Marine Systems. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Marine Systems, [VOL 123, (01.08.13)] DOI 10.1016/j.jmarsys.2013.04.004". The full text is under embargo until 01.08.15

First stellar photons for an integrated optics discrete beam combiner at the William Herschel Telescope

We present the first on-sky results of a four-telescope integrated optics discrete beam combiner (DBC) tested at the 4.2mWilliamHerschel Telescope. The device consists of a four-input pupil remapper followed by a DBC and a 23-output reformatter. The whole device was written monolithically in a single alumino-borosilicate substrate using ultrafast laser inscription. The device was operated at astronomical H-band (1.6 μm), and a deformable mirror along with a microlens array was used to inject stellar photons into the device. We report the measured visibility amplitudes and closure phases obtained on Vega and Altair that are retrieved using the calibrated transfer matrix of the device. While the coherence function can be reconstructed, the on-sky results show significant dispersion from the expected values. Based on the analysis of comparable simulations, we find that such dispersion is largely caused by the limited signal-to-noise ratio of our observations. This constitutes a first step toward an improved validation of theDBCas a possible beam combination scheme for long-baseline interferometry. © 2021 Optical Society of America

Planetary Candidates Observed by Kepler. VIII. A Fully Automated Catalog With Measured Completeness and Reliability Based on Data Release 25

We present the Kepler Object of Interest (KOI) catalog of transiting exoplanets based on searching four years of Kepler time series photometry (Data Release 25, Q1-Q17). The catalog contains 8054 KOIs of which 4034 are planet candidates with periods between 0.25 and 632 days. Of these candidates, 219 are new and include two in multi-planet systems (KOI-82.06 and KOI-2926.05), and ten high-reliability, terrestrial-size, habitable zone candidates. This catalog was created using a tool called the Robovetter which automatically vets the DR25 Threshold Crossing Events (TCEs, Twicken et al. 2016). The Robovetter also vetted simulated data sets and measured how well it was able to separate TCEs caused by noise from those caused by low signal-to-noise transits. We discusses the Robovetter and the metrics it uses to sort TCEs. For orbital periods less than 100 days the Robovetter completeness (the fraction of simulated transits that are determined to be planet candidates) across all observed stars is greater than 85%. For the same period range, the catalog reliability (the fraction of candidates that are not due to instrumental or stellar noise) is greater than 98%. However, for low signal-to-noise candidates between 200 and 500 days around FGK dwarf stars, the Robovetter is 76.7% complete and the catalog is 50.5% reliable. The KOI catalog, the transit fits and all of the simulated data used to characterize this catalog are available at the NASA Exoplanet Archive.Comment: 61 pages, 23 Figures, 9 Tables, Accepted to The Astrophysical Journal Supplement Serie