Distance constraints on activation of TRPV4 channels by AKAP150-bound PKCα in arterial myocytes.

TRPV4 (transient receptor potential vanilloid 4) channels are Ca2+-permeable channels that play a key role in regulating vascular tone. In arterial myocytes, opening of TRPV4 channels creates local increases in Ca2+ influx, detectable optically as "TRPV4 sparklets." TRPV4 sparklet activity can be enhanced by the action of the vasoconstrictor angiotensin II (AngII). This modulation depends on the activation of subcellular signaling domains that comprise protein kinase C α (PKCα) bound to the anchoring protein AKAP150. Here, we used super-resolution nanoscopy, patch-clamp electrophysiology, Ca2+ imaging, and mathematical modeling approaches to test the hypothesis that AKAP150-dependent modulation of TRPV4 channels is critically dependent on the distance between these two proteins in the sarcolemma of arterial myocytes. Our data show that the distance between AKAP150 and TRPV4 channel clusters varies with sex and arterial bed. Consistent with our hypothesis, we further find that basal and AngII-induced TRPV4 channel activity decays exponentially as the distance between TRPV4 and AKAP150 increases. Our data suggest a maximum radius of action of ∼200 nm for local modulation of TRPV4 channels by AKAP150-associated PKCα

Benefits of daddy play

The Fathers’ Engagement Project was designed to assess the impact and feasibility of a six week physically active play based programme on fathers’ engagement with their three to five year old children. Sessions were held at City based Children’s Centres. Fathers’ engagement and attitudes to child PA were measured pre- and post-intervention via questionnaire. Acceptability of the intervention was explored through participant and staff focus groups. Results from questionnaires showed that fathers felt more in control of their children and had increased awareness of their role in motivating their child to play. Fathers also suggested that sessions provided opportunities to spend quality time with their children despite there being no significant increase in the overall time fathers self-reported spending with their child during the week or at the weekend. A number of recommendations for both research and practice are provided

Global marine bacterial diversity peaks at high latitudes in winter.

Genomic approaches to characterizing bacterial communities are revealing significant differences in diversity and composition between environments. But bacterial distributions have not been mapped at a global scale. Although current community surveys are way too sparse to map global diversity patterns directly, there is now sufficient data to fit accurate models of how bacterial distributions vary across different environments and to make global scale maps from these models. We apply this approach to map the global distributions of bacteria in marine surface waters. Our spatially and temporally explicit predictions suggest that bacterial diversity peaks in temperate latitudes across the world's oceans. These global peaks are seasonal, occurring 6 months apart in the two hemispheres, in the boreal and austral winters. This pattern is quite different from the tropical, seasonally consistent diversity patterns observed for most macroorganisms. However, like other marine organisms, surface water bacteria are particularly diverse in regions of high human environmental impacts on the oceans. Our maps provide the first picture of bacterial distributions at a global scale and suggest important differences between the diversity patterns of bacteria compared with other organisms

Bayesian Power Spectrum Analysis of the First-Year WMAP data

We present the first results from a Bayesian analysis of the WMAP first year data using a Gibbs sampling technique. Using two independent, parallel supercomputer codes we analyze the WMAP Q, V and W bands. The analysis results in a full probabilistic description of the information the WMAP data set contains about the power spectrum and the all-sky map of the cosmic microwave background anisotropies. We present the complete probability distributions for each C_l including any non-Gaussianities of the power spectrum likelihood. While we find good overall agreement with the previously published WMAP spectrum, our analysis uncovers discrepancies in the power spectrum estimates at low l multipoles. For example we claim the best-fit Lambda-CDM model is consistent with the C_2 inferred from our combined Q+V+W analysis with a 10% probability of an even larger theoretical C_2. Based on our exact analysis we can therefore attribute the "low quadrupole issue" to a statistical fluctuation.Comment: 5 pages. 4 figures. For additional information and data see http://www.astro.uiuc.edu/~iodwyer/research#wma

Dysphonia and dysphagia consequences of paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS)

IMPORTANCE: Paediatric inflammatory multisystem syndrome, temporally associated with SARS-CoV-2 (PIMS-TS) is a novel disease first identified in 2020. Recent cohort studies have described the complex presentation and symptomatology. This paper provides detailed description of the dysphagia and dysphonia symptoms, management, and outcome. OBJECTIVE: To describe dysphagia and dysphonia in PIMS-TS. DESIGN: Retrospective cohort study. SETTING: Single tertiary and quaternary children's hospital. PARTICIPANTS: All 50 children treated for paediatric multisystem inflammatory disease between April and June 2020 were included in this study. MAIN OUTCOME(S) AND MEASURE(S): Dysphonia: GRBAS Perceptual Severity Scores, Vocal Handicap Index scores and the Vocal Tract Discomfort Scale. Dysphagia: Functional Oral Intake Scale. RESULTS: Fifty children met the diagnostic criteria for PIMS-TS. 33 (66%) were male. Median age was 10 years (range: 1–17). 36 (72%) were of Black, Asian or minority ethnic background. Nine (18%) required specialist assessment and management of dysphagia and/or dysphonia. Five (55%) were male with a median age of 9 years 7 months (range: 1–15 years). Symptoms typically resolved within three months. Two children presented with persisting dysphonia three months post-presentation. Neurological, inflammatory, and iatrogenic causes of dysphagia and dysphonia were identified. CONCLUSIONS AND RELEVANCE: Dysphonia and dysphagia are present in children with PIMS-TS. Further data is required to understand pathophysiology, estimate incidence, and determine prognostic factors. This preliminary data highlights the need for dysphagia and dysphonia screening and timely referral for specialist, multidisciplinary assessment and treatment to ensure short-term aspiration risk is managed and long-term, functional outcomes are optimised

A re-analysis of the three-year WMAP temperature power spectrum and likelihood

We analyze the three-year WMAP temperature anisotropy data seeking to confirm the power spectrum and likelihoods published by the WMAP team. We apply five independent implementations of four algorithms to the power spectrum estimation and two implementations to the parameter estimation. Our single most important result is that we broadly confirm the WMAP power spectrum and analysis. Still, we do find two small but potentially important discrepancies: On large angular scales there is a small power excess in the WMAP spectrum (5-10% at l<~30) primarily due to likelihood approximation issues between 13 <= l <~30. On small angular scales there is a systematic difference between the V- and W-band spectra (few percent at l>~300). Recently, the latter discrepancy was explained by Huffenberger et al. (2006) in terms of over-subtraction of unresolved point sources. As far as the low-l bias is concerned, most parameters are affected by a few tenths of a sigma. The most important effect is seen in n_s. For the combination of WMAP, Acbar and BOOMERanG, the significance of n_s =/ 1 drops from ~2.7 sigma to ~2.3 sigma when correcting for this bias. We propose a few simple improvements to the low-l WMAP likelihood code, and introduce two important extensions to the Gibbs sampling method that allows for proper sampling of the low signal-to-noise regime. Finally, we make the products from the Gibbs sampling analysis publically available, thereby providing a fast and simple route to the exact likelihood without the need of expensive matrix inversions.Comment: 14 pages, 7 figures. Accepted for publication in ApJ. Numerical results unchanged, but interpretation sharpened: Likelihood approximation issues at l=13-30 far more important than potential foreground issues at l <= 12. Gibbs products (spectrum and sky samples, and "easy-to-use" likelihood module) available from http://www.astro.uio.no/~hke/ under "Research

Multiple indices of diffusion identifies white matter damage in mild cognitive impairment and Alzheimer's disease

The study of multiple indices of diffusion, including axial (DA), radial (DR) and mean diffusion (MD), as well as fractional anisotropy (FA), enables WM damage in Alzheimer's disease (AD) to be assessed in detail. Here, tract-based spatial statistics (TBSS) were performed on scans of 40 healthy elders, 19 non-amnestic MCI (MCIna) subjects, 14 amnestic MCI (MCIa) subjects and 9 AD patients. Significantly higher DA was found in MCIna subjects compared to healthy elders in the right posterior cingulum/precuneus. Significantly higher DA was also found in MCIa subjects compared to healthy elders in the left prefrontal cortex, particularly in the forceps minor and uncinate fasciculus. In the MCIa versus MCIna comparison, significantly higher DA was found in large areas of the left prefrontal cortex. For AD patients, the overlap of FA and DR changes and the overlap of FA and MD changes were seen in temporal, parietal and frontal lobes, as well as the corpus callosum and fornix. Analysis of differences between the AD versus MCIna, and AD versus MCIa contrasts, highlighted regions that are increasingly compromised in more severe disease stages. Microstructural damage independent of gross tissue loss was widespread in later disease stages. Our findings suggest a scheme where WM damage begins in the core memory network of the temporal lobe, cingulum and prefrontal regions, and spreads beyond these regions in later stages. DA and MD indices were most sensitive at detecting early changes in MCIa

Lineshape of the thermopower of quantum dots

Quantum dots are an important model system for thermoelectric phenomena, and may be used to enhance the thermal-to-electric energy conversion efficiency in functional materials. It is therefore important to obtain a detailed understanding of a quantum-dot's thermopower as a function of the Fermi energy. However, so far it has proven difficult to take effects of co-tunnelling into account in the interpretation of experimental data. Here we show that a single-electron tunnelling model, using knowledge of the dot's electrical conductance which in fact includes all-order co-tunneling effects, predicts the thermopower of quantum dots as a function of the relevant energy scales, in very good agreement with experiment.Comment: 10 pages, 5 figure

EQ-5D-5L versus 3L: the impact on cost-effectiveness

Objectives To model the relationship between EQ-5D-3L and EQ-5D-5L and examine how differences impact on cost-effectiveness in case studies. Methods We used two datasets that included both EQ-5D-3L and EQ-5D-3L from the same respondents. The EuroQoL dataset (n=3551) included patients with different diseases and a healthy cohort. The National Databank (NDB) dataset included patients with rheumatoid disease (n=5205). We estimated a system of ordinal regressions in each dataset using copula models, to link responses to the 3L instrument to 5L and its tariff, and vice versa. Results were applied to nine cost-effectiveness studies. Results Best-fitting models differed between EuroQoL and NDB datasets in terms of the explanatory variables, copulas and coefficients. In both cases the coefficients of the covariates and latent factor between -3L and -5L were significantly different, indicating that the two instruments are not a uniform realignment of the response levels for most dimensions. In the case studies, moving from 3L to 5L caused a decrease of up to 87% in incremental QALYs gained from effective technologies in almost all cases. ICERs increased, often substantially. Conversely, one technology with a significant mortality gain saw increased incremental QALYs. Conclusion 5L shifts mean utility scores up the utility scale towards full health and compresses them into a smaller range, compared to -3L. Improvements in quality of life are valued less using 5L than with 3L. 3L and 5L can produce substantially different estimates of cost effectiveness. There is no simple proportional adjustment that can be made to reconcile these differences