What is the problem?: Evidence, politics and alcohol policy in England and Wales, 2010–2014

This article considers alcohol policy development in England and Wales under the coalition government after 2010. With a particular focus on minimum unit pricing, it examines why policy departures based on supply-side controls drawn from public health models were abandoned in favour of a restoration of policy equilibrium. This article adopts a historically informed political science perspective, drawing upon insights from John Kingdon’s policy streams approach, with a focus on how the “alcohol problem” is defined and framed by policy actors. It argues that while the restoration of policy equilibrium was significantly attributable to industry lobbying, also important were the inconsistent framing of policy proposals, lack of departmental synergy, ideological tensions and a lack of coherence in the communication of evidence

Understanding gas capacity, guest selectivity and diffusion in porous liquids

Porous liquids are a new class of material that could have applications in areas such as gas separation and homogeneous catalysis. Here we use a combination of measurement techniques, molecular simulations, and control experiments to advance the quantitative understanding of these liquids. In particular, we show that the cage cavities remain unoccupied in the absence of a suitable guest, and that the liquids can adsorb large quantities of gas, with gas occupancy in the cages as high as 72% and 74% for Xe and SF6, respectively. Gases can be reversibly loaded and released by using non-chemical triggers such as sonication, suggesting potential for gas separation schemes. Diffusion NMR experiments show that gases are in dynamic equilibrium between a bound and unbound state in the cage cavities, in agreement with recent simulations for related porous liquids. Comparison with gas adsorption in porous organic cage solids suggests that porous liquids have similar gas binding affinities, and that the physical properties of the cage molecule are translated into the liquid state. By contrast, some physical properties are different: for example, solid homochiral porous cages show enantioselectivity for chiral aromatic alcohols, whereas the equivalent homochiral porous liquids do not. This can be attributed to a loss of supramolecular organisation in the isotropic porous liquid

Resonant tunnelling into the two-dimensional subbands of InSe layers

Two-dimensional (2D) van der Waals (vdW) crystals have attracted considerable interest for digital electronics beyond Si-based complementary metal oxide semiconductor technologies. Despite the transformative success of Si-based devices, there are limits to their miniaturization and functionalities. Here we realize a resonant tunnelling transistor (RTT) based on a 2D InSe layer sandwiched between two multi-layered graphene (MLG) electrodes. In the RTT the energy of the quantum-confined 2D subbands of InSe can be tuned by the thickness of the InSe layer. By applying a voltage across the two MLG electrodes, which serve as the source and drain electrodes to the InSe, the chemical potential in the source can be tuned in and out of resonance with a given 2D subband, leading to multiple regions of negative differential conductance that can be additionally tuned by electrostatic gating. This work demonstrates the potential of InSe and InSe-based RTTs for applications in quantum electronics.

Impaired postprandial skeletal muscle vascular responses to a mixed meal challenge in normoglycaemic people with a parent with type 2 diabetes

Aims/hypothesis: Microvascular blood flow (MBF) increases in skeletal muscle postprandially to aid in glucose delivery and uptake in muscle. This vascular action is impaired in individuals who are obese or have type 2 diabetes. Whether MBF is impaired in normoglycaemic people at risk of type 2 diabetes is unknown. We aimed to determine whether apparently healthy people at risk of type 2 diabetes display impaired skeletal muscle microvascular responses to a mixed-nutrient meal. Methods: In this cross-sectional study, participants with no family history of type 2 diabetes (FH-) for two generations (n = 18), participants with a positive family history of type 2 diabetes (FH+; i.e. a parent with type 2 diabetes; n = 16) and those with type 2 diabetes (n = 12) underwent a mixed meal challenge (MMC). Metabolic responses (blood glucose, plasma insulin and indirect calorimetry) were measured before and during the MMC. Skeletal muscle large artery haemodynamics (2D and Doppler ultrasound, and Mobil-O-graph) and microvascular responses (contrast-enhanced ultrasound) were measured at baseline and 1 h post MMC. Results: Despite normal blood glucose concentrations, FH+ individuals displayed impaired metabolic flexibility (reduced ability to switch from fat to carbohydrate oxidation vs FH-; p \u3c 0.05) during the MMC. The MMC increased forearm muscle microvascular blood volume in both the FH- (1.3-fold, p \u3c 0.01) and FH+ (1.3-fold, p \u3c 0.05) groups but not in participants with type 2 diabetes. However, the MMC increased MBF (1.9-fold, p \u3c 0.01), brachial artery diameter (1.1-fold, p \u3c 0.01) and brachial artery blood flow (1.7-fold, p \u3c 0.001) and reduced vascular resistance (0.7-fold, p \u3c 0.001) only in FH- participants, with these changes being absent in FH+ and type 2 diabetes. Participants with type 2 diabetes displayed significantly higher vascular stiffness (p \u3c 0.001) compared with those in the FH- and FH+ groups; however, vascular stiffness did not change during the MMC in any participant group. Conclusions/interpretation: Normoglycaemic FH+ participants display impaired postprandial skeletal muscle macro- and microvascular responses, suggesting that poor vascular responses to a meal may contribute to their increased risk of type 2 diabetes. We conclude that vascular insulin resistance may be an early precursor to type 2 diabetes in humans, which can be revealed using an MMC

AIITS: Preliminary light scattering data from Tropical Tropopause Layer cirrus

The new optical particle spectrometer AIITS (Aerosol Ice Interface Transition Spectrometer) is the next instrument in the Small Ice Detector (SID) family. Like SID3, it acquires two-dimensional forward scattering patterns from particles in the size range from about one to a few hundred micrometers (depending on variable settings). The patterns allow quantifying the phase, habit and fine surface features of large aerosol and ice crystals, which are frequently too small to be adequately characterised using traditional imaging techniques.Two 2D-forward scattering patterns are recorded per particle using two high-resolution cameras. The cameras fire simultaneously, recording the scattering pattern via a beamsplitter. AIITS can be configured such that the cameras measure either perpendicular polarisations (i.e. P-polarisation with one camera, S-polarisation with the other) or to have a different gain setting on each camera to encompass a larger dynamic range. The incident beam can be either circularly or linearly polarised. Backscatter depolarisation is also measured. The camera and beam configuration must be selected pre-flight.The probe was deployed on board the NASA Global Hawk aircraft during a recent ATTREX/CAST campaign over the tropical eastern Pacific. We present preliminary results from a case study from the 5th of March 2015 which showed the existence of a variety of particles, including rough surfaced ice crystals, some regular, hexagonal ones, as well as particles with smooth, curved surfaces (but not spherical). We compare AIITS data with co-located particle imaging from the SPEC Hawkeye probe.The Hawkeye probe combines a 2D-Stereo optical array probe, a Cloud Particle Imager (CPI), and a Fast Cloud Droplet Probe (FCDP) to provide high resolution images (2.3 micron pixel resolution) and particle size distributions of concentration, area, and mass for particles with diameter between one micron and a few centimeters.The TTL is known to be of importance due to the presence of subvisual cirrus, which contributes to net climate radiative feedback. Knowledge of the processes involved in the creation and persistence of such clouds is limited due to sparse observational data.Non peer reviewe

Learning by exporting:lessons from high-technology SMEs

We investigate the learning by exporting hypothesis by examining the effect of exporting on the subsequent innovation performance of a sample of high-technology SMEs based in the UK. We find evidence of learning by exporting, but the pattern of this effect is complex. Exporting helps high-tech SMEs innovate subsequently, but does not make them more innovation intensive. There is evidence that consistent exposure to export markets helps firms overcome the innovation hurdle, but that there is a positive scale effect of exposure to export markets which allows innovative firms to sell more of their new-to-market products on entering export markets. Service sector firms are able to reap the benefits of exposure to export markets at an earlier (entry) stage of the internationalization process than are manufacturing firms. Innovation-intensive firms exhibit a different pattern of entry to and exit from export markets from low-intensity innovators, and this is reflected in different effects of exporting

A bioimage informatics platform for high-throughput embryo phenotyping

High-throughput phenotyping is a cornerstone of numerous functional genomics projects. In recent years, imaging screens have become increasingly important in understanding gene–phenotype relationships in studies of cells, tissues and whole organisms. Three-dimensional (3D) imaging has risen to prominence in the field of developmental biology for its ability to capture whole embryo morphology and gene expression, as exemplified by the International Mouse Phenotyping Consortium (IMPC). Large volumes of image data are being acquired by multiple institutions around the world that encompass a range of modalities, proprietary software and metadata. To facilitate robust downstream analysis, images and metadata must be standardized to account for these differences. As an open scientific enterprise, making the data readily accessible is essential so that members of biomedical and clinical research communities can study the images for themselves without the need for highly specialized software or technical expertise. In this article, we present a platform of software tools that facilitate the upload, analysis and dissemination of 3D images for the IMPC. Over 750 reconstructions from 80 embryonic lethal and subviable lines have been captured to date, all of which are openly accessible at mousephenotype.org. Although designed for the IMPC, all software is available under an open-source licence for others to use and develop further. Ongoing developments aim to increase throughput and improve the analysis and dissemination of image data. Furthermore, we aim to ensure that images are searchable so that users can locate relevant images associated with genes, phenotypes or human diseases of interest

How achievable are COVID-19 clinical trial recruitment targets? A UK observational cohort study and trials registry analysis

Objectives: To analyse enrolment to interventional trials during the first wave of the COVID-19 pandemic in England and describe the barriers to successful recruitment in the circumstance of a further wave or future pandemics. Design: We analysed registered interventional COVID-19 trial data and concurrently did a prospective observational study of hospitalised patients with COVID-19 who were being assessed for eligibility to one of the RECOVERY, C19-ACS or SIMPLE trials. Setting: Interventional COVID-19 trial data were analysed from the clinicaltrials.gov and International Standard Randomized Controlled Trial Number databases on 12 July 2020. The patient cohort was taken from five centres in a respiratory National Institute for Health Research network. Population and modelling data were taken from published reports from the UK government and Medical Research Council Biostatistics Unit. Participants: 2082 consecutive admitted patients with laboratory-confirmed SARS-CoV-2 infection from 27 March 2020 were included. Main outcome measures: Proportions enrolled, and reasons for exclusion from the aforementioned trials. Comparisons of trial recruitment targets with estimated feasible recruitment numbers. Results: Analysis of trial registration data for COVID-19 treatment studies enrolling in England showed that by 12 July 2020, 29 142 participants were needed. In the observational study, 430 (20.7%) proceeded to randomisation. 82 (3.9%) declined participation, 699 (33.6%) were excluded on clinical grounds, 363 (17.4%) were medically fit for discharge and 153 (7.3%) were receiving palliative care. With 111 037 people hospitalised with COVID-19 in England by 12 July 2020, we determine that 22 985 people were potentially suitable for trial enrolment. We estimate a UK hospitalisation rate of 2.38%, and that another 1.25 million infections would be required to meet recruitment targets of ongoing trials. Conclusions: Feasible recruitment rates, study design and proliferation of trials can limit the number, and size, that will successfully complete recruitment. We consider that fewer, more appropriately designed trials, prioritising cooperation between centres would maximise productivity in a further wave