Photonic band structure of highly deformable, self-assembling systems

We calculate the photonic band structure at normal incidence of highly deformable, self-assembling systems - cholesteric elastomers subjected to external stress. Cholesterics display brilliant reflection and lasing owing to gaps in their photonic band structure. The band structure of cholesteric elastomers varies sensitively with strain, showing new gaps opening up and shifting in frequency. A novel prediction of a total band gap is made, and is expected to occur in the vicinity of the previously observed de Vries bandgap, which is only for one polarisation

Mouse Retinal Development: a Dark Horse Model for Systems Biology Research

The developing retina is an excellent model to study cellular fate determination and differentiation in the context of a complex tissue. Over the last decade, many basic principles and key genes that underlie these processes have been experimentally identified. In this review, we construct network models to summarize known gene interactions that underlie determination and fundamentally affect differentiation of each retinal cell type. These networks can act as a scaffold to assemble subsequent discoveries. In addition, these summary networks provide a rational segue to systems biology approaches necessary to understand the many events leading to appropriate cellular determination and differentiation in the developing retina and other complex tissues

Atom lasers: production, properties and prospects for precision inertial measurement

We review experimental progress on atom lasers out-coupled from Bose-Einstein condensates, and consider the properties of such beams in the context of precision inertial sensing. The atom laser is the matter-wave analog of the optical laser. Both devices rely on Bose-enhanced scattering to produce a macroscopically populated trapped mode that is output-coupled to produce an intense beam. In both cases, the beams often display highly desirable properties such as low divergence, high spectral flux and a simple spatial mode that make them useful in practical applications, as well as the potential to perform measurements at or below the quantum projection noise limit. Both devices display similar second-order correlations that differ from thermal sources. Because of these properties, atom lasers are a promising source for application to precision inertial measurements.Comment: This is a review paper. It contains 40 pages, including references and figure

Designing and implementing sample and data collection for an international genetics study: the Type 1 Diabetes Genetics Consortium (T1DGC)

Background and Purpose The Type 1 Diabetes Genetics Consortium (T1DGC) is an international project whose primary aims are to: (a) discover genes that modify type 1 diabetes risk; and (b) expand upon the existing genetic resources for type 1 diabetes research. The initial goal was to collect 2500 affected sibling pair (ASP) families worldwide

Interferometry with independent Bose-Einstein ondensates: parity as an EPR/Bell quantum variable

When independent Bose-Einstein condensates (BEC), described quantum mechanically by Fock (number) states, are sent into interferometers, the measurement of the output port at which the particles are detected provides a binary measurement, with two possible results $\pm1$. With two interferometers and two BEC's, the parity (product of all results obtained at each interferometer) has all the features of an Einstein-Podolsky-Rosen quantity, with perfect correlations predicted by quantum mechanics when the settings (phase shifts of the interferometers) are the same. When they are different, significant violations of Bell inequalities are obtained. These violations do not tend to zero when the number $N$ of particles increases, and can therefore be obtained with arbitrarily large systems, but a condition is that all particles should be detected. We discuss the general experimental requirements for observing such effects, the necessary detection of all particles in correlation, the role of the pixels of the CCD detectors, and that of the alignments of the interferometers in terms of matching of the wave fronts of the sources in the detection regions. Another scheme involving three interferometers and three BEC's is discussed; it leads to Greenberger Horne Zeilinger (GHZ) sign contradictions, as in the usual GHZ case with three particles, but for an arbitrarily large number of them. Finally, generalizations of the Hardy impossibilities to an arbitrarily large number of particles are introduced. BEC's provide a large versality for observing violations of local realism in a variety of experimental arrangements.Comment: appendix adde

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript