Characterizing the epoch of reionization with the small-scale CMB: Constraints on the optical depth and duration

Patchy reionization leaves a number of imprints on the small-scale cosmic microwave background (CMB) temperature fluctuations, the largest of which is the kinematic Sunyaev-Zel'dovich (kSZ), the Doppler shift of CMB photons scattering off moving electrons in ionized bubbles. It has long been known that in the CMB power spectrum, this imprint of reionization is largely degenerate with the kSZ signal produced by late-time galaxies and clusters, thus limiting our ability to constrain reionization. Following Smith & Ferraro (2017), it is possible to isolate the reionization contribution in a model independent way, by looking at the large scale modulation of the small scale CMB power spectrum. In this paper we extend the formalism to use the full shape information of the small scale power spectrum (rather than just its broadband average), and argue that this is necessary to break the degeneracy between the optical depth τ and parameters setting the duration of reionization. In particular, we show that the next generation of CMB experiments could achieve up to a factor of 3 improvement on the optical depth τ and at the same time, constrain the duration of reionization to ∼25%. This can help tighten the constrains on neutrino masses, which will be limited by our knowledge of τ, and shed light on the physical processes responsible for reionization

Patients' practices and experiences of using nebuliser therapy in the management of COPD at home.

How patients use their nebulisers at home is vital to ensure effective treatment and optimal health outcomes for patients with chronic obstructive pulmonary disease (COPD). The aim of the study was to identify the practicalities and problems associated with nebuliser use by patients with COPD at home, which may impact on the safety and effectiveness of therapy

The influence of submesoscales and vertical mixing on the export of sinking tracers in large-eddy simulations

AbstractWe use idealized large-eddy simulations (LES) and a simple analytical theory to study the influence of submesoscales on the concentration and export of sinking particles from the mixed layer. We find that restratification of the mixed layer following the development of submesoscales reduces the rate of vertical mixing which, in turn, enhances the export rate associated with gravitational settling. For a neutral tracer initially confined to the mixed layer, subinertial (submesoscale) motions enhance the downward tracer flux, consistent with previous studies. However, the sign of the advective flux associated with the concentration of sinking particles reverses, indicating reentrainment into the mixed layer. A new theory is developed to model the gravitational settling flux when the particle concentration is nonuniform. The theory broadly agrees with the LES results and allows us to extend the analysis to a wider range of parameters.</jats:p

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Gene therapy restores vision in rd1 mice after removal of a confounding mutation in Gpr179

The rd1 mouse with a mutation in the Pde6b gene was the first strain of mice identified with a retinal degeneration. However, AAV-mediated gene supplementation of rd1 mice only results in structural preservation of photoreceptors, and restoration of the photoreceptor-mediated a-wave, but not in restoration of the bipolar cell-mediated b-wave. Here we show that a mutation in Gpr179 prevents the full restoration of vision in rd1 mice. Backcrossing rd1 with C57BL6 mice reveals the complete lack of b-wave in a subset of mice, consistent with an autosomal recessive Mendelian inheritance pattern. We identify a mutation in the Gpr179 gene, which encodes for a G-protein coupled receptor localized to the dendrites of ON-bipolar cells. Gene replacement in rd1 mice that are devoid of the mutation in Gpr179 successfully restores the function of both photoreceptors and bipolar cells, which is maintained for up to 13 months. Our discovery may explain the failure of previous gene therapy attempts in rd1 mice, and we propose that Grp179 mutation status should be taken into account in future studies involving rd1 mice

Complete analysis of the B-cell response to a protein antigen, from in vivo germinal centre formation to 3-D modelling of affinity maturation

Somatic hypermutation of immunoglobulin variable region genes occurs within germinal centres (GCs) and is the process responsible for affinity maturation of antibodies during an immune response. Previous studies have focused almost exclusively on the immune response to haptens, which may be unrepresentative of epitopes on protein antigens. In this study, we have exploited a model system that uses transgenic B and CD4&lt;sup&gt;+&lt;/sup&gt; T cells specific for hen egg lysozyme (HEL) and a chicken ovalbumin peptide, respectively, to investigate a tightly synchronized immune response to protein antigens of widely differing affinities, thus allowing us to track many facets of the development of an antibody response at the antigen-specific B cell level in an integrated system &lt;i&gt;in&lt;/i&gt; &lt;i&gt;vivo&lt;/i&gt;. Somatic hypermutation of immunoglobulin variable genes was analysed in clones of transgenic B cells proliferating in individual GCs in response to HEL or the cross-reactive low-affinity antigen, duck egg lysozyme (DEL). Molecular modelling of the antibody–antigen interface demonstrates that recurring mutations in the antigen-binding site, selected in GCs, enhance interactions of the antibody with DEL. The effects of these mutations on affinity maturation are demonstrated by a shift of transgenic serum antibodies towards higher affinity for DEL in DEL-cOVA immunized mice. The results show that B cells with high affinity antigen receptors can revise their specificity by somatic hypermutation and antigen selection in response to a low-affinity, cross-reactive antigen. These observations shed further light on the nature of the immune response to pathogens and autoimmunity and demonstrate the utility of this novel model for studies of the mechanisms of somatic hypermutation

Intensities and self-broadening coefficients of the strongest water vapour lines in the 2.7 and 6.25 mu m absorption bands

Intensities and self-broadening coefficients are presented for about 460 of the strongest water vapour lines in the spectral regions 1400–1840 cm−1 and 3440–3970 cm^{-1} at room temperature, obtained from rather unique measurements using a 5-mm-path-length cell. The retrieved spectral line parameters are compared with those in the HITRAN database ver. 2008 and 2012 and with recent ab-initio calculations. Both the retrieved intensities and half-widths are on average in reasonable agreement with those in HITRAN-2012. Maximum systematic differences do not exceed 4% for intensities (1600 cm^{-1} band) and 7% for self-broadening coefficients (3600 cm^{-1} band). For many lines however significant disagreements were detected with the HITRAN-2012 data, exceeding the average uncertainty of the retrieval. In addition, water vapour line parameters for 5300 cm^{-1} (1.9 μm) band reported by us in 2005 were also compared with HITRAN-2012, and show average differences of 4–5% for both intensities and half-widths

Risk Adjustment In Neurocritical care (RAIN)--prospective validation of risk prediction models for adult patients with acute traumatic brain injury to use to evaluate the optimum location and comparative costs of neurocritical care: a cohort study.

OBJECTIVES: To validate risk prediction models for acute traumatic brain injury (TBI) and to use the best model to evaluate the optimum location and comparative costs of neurocritical care in the NHS. DESIGN: Cohort study. SETTING: Sixty-seven adult critical care units. PARTICIPANTS: Adult patients admitted to critical care following actual/suspected TBI with a Glasgow Coma Scale (GCS) score of < 15. INTERVENTIONS: Critical care delivered in a dedicated neurocritical care unit, a combined neuro/general critical care unit within a neuroscience centre or a general critical care unit outside a neuroscience centre. MAIN OUTCOME MEASURES: Mortality, Glasgow Outcome Scale - Extended (GOSE) questionnaire and European Quality of Life-5 Dimensions, 3-level version (EQ-5D-3L) questionnaire at 6 months following TBI. RESULTS: The final Risk Adjustment In Neurocritical care (RAIN) study data set contained 3626 admissions. After exclusions, 3210 patients with acute TBI were included. Overall follow-up rate at 6 months was 81%. Of 3210 patients, 101 (3.1%) had no GCS score recorded and 134 (4.2%) had a last pre-sedation GCS score of 15, resulting in 2975 patients for analysis. The most common causes of TBI were road traffic accidents (RTAs) (33%), falls (47%) and assault (12%). Patients were predominantly young (mean age 45 years overall) and male (76% overall). Six-month mortality was 22% for RTAs, 32% for falls and 17% for assault. Of survivors at 6 months with a known GOSE category, 44% had severe disability, 30% moderate disability and 26% made a good recovery. Overall, 61% of patients with known outcome had an unfavourable outcome (death or severe disability) at 6 months. Between 35% and 70% of survivors reported problems across the five domains of the EQ-5D-3L. Of the 10 risk models selected for validation, the best discrimination overall was from the International Mission for Prognosis and Analysis of Clinical Trials in TBI Lab model (IMPACT) (c-index 0.779 for mortality, 0.713 for unfavourable outcome). The model was well calibrated for 6-month mortality but substantially underpredicted the risk of unfavourable outcome at 6 months. Baseline patient characteristics were similar between dedicated neurocritical care units and combined neuro/general critical care units. In lifetime cost-effectiveness analysis, dedicated neurocritical care units had higher mean lifetime quality-adjusted life-years (QALYs) at small additional mean costs with an incremental cost-effectiveness ratio (ICER) of £14,000 per QALY and incremental net monetary benefit (INB) of £17,000. The cost-effectiveness acceptability curve suggested that the probability that dedicated compared with combined neurocritical care units are cost-effective is around 60%. There were substantial differences in case mix between the 'early' (within 18 hours of presentation) and 'no or late' (after 24 hours) transfer groups. After adjustment, the 'early' transfer group reported higher lifetime QALYs at an additional cost with an ICER of £11,000 and INB of £17,000. CONCLUSIONS: The risk models demonstrated sufficient statistical performance to support their use in research but fell below the level required to guide individual patient decision-making. The results suggest that management in a dedicated neurocritical care unit may be cost-effective compared with a combined neuro/general critical care unit (although there is considerable statistical uncertainty) and support current recommendations that all patients with severe TBI would benefit from transfer to a neurosciences centre, regardless of the need for surgery. We recommend further research to improve risk prediction models; consider alternative approaches for handling unobserved confounding; better understand long-term outcomes and alternative pathways of care; and explore equity of access to postcritical care support for patients following acute TBI. FUNDING: The National Institute for Health Research Health Technology Assessment programme