An acoustic image-source characterisation of surface profiles

The image-source method models the specular reflection from a plane by means of a secondary source positioned at the source's reflected image. The method has been widely used in acoustics to model the reverberant field of rectangular rooms, but can also be used for general-shaped rooms and non-flat reflectors. This paper explores the relationship between the physical properties of a non-flat reflector and the statistical properties of the associated cloud of image-sources. It is shown here that the standard deviation of the image-sources is strongly correlated with the ratio between depth and width of the reflector's spatial features

CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity

Cancer cells exploit the expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) to subvert T-cell-mediated immunosurveillance. The success of therapies that disrupt PD-L1-mediated tumour tolerance has highlighted the need to understand the molecular regulation of PD-L1 expression1. Here we identify the uncharacterized protein CMTM6 as a critical regulator of PD-L1 in a broad range of cancer cells, by using a genome-wide CRISPR–Cas9 screen. CMTM6 is a ubiquitously expressed protein that binds PD-L1 and maintains its cell surface expression. CMTM6 is not required for PD-L1 maturation but co-localizes with PD-L1 at the plasma membrane and in recycling endosomes, where it prevents PD-L1 from being targeted for lysosome-mediated degradation. Using a quantitative approach to profile the entire plasma membrane proteome, we find that CMTM6 displays specificity for PD-L1. Notably, CMTM6 depletion decreases PD-L1 without compromising cell surface expression of MHC class I. CMTM6 depletion, via the reduction of PD-L1, significantly alleviates the suppression of tumour-specific T cell activity in vitro and in vivo. These findings provide insights into the biology of PD-L1 regulation, identify a previously unrecognized master regulator of this critical immune checkpoint and highlight a potential therapeutic target to overcome immune evasion by tumour cells.M.L.B. is supported by a Cancer Research UK Clinician Scientist Fellowship (C53779/A20097), Addenbrooke’s Charitable Trust award and NIHR fellowship. P.J.L. is supported by a Wellcome Trust PRF (101835/Z/13/Z) and work in the Lehner laboratory is supported by NHSBT, NIHR Cambridge BRC, a Wellcome Trust Strategic Award to CIMR, and the Addenbrooke’s Charitable Trust M.A.D. is supported by a Senior Leukaemia Foundation Australia Fellowship and work in the Dawson laboratory is supported by the NHMRC (Grants 1085015, 1106444 and 1106447) Cancer Council Victoria and Leukaemia Foundation Australia. Cancer Research UK (C53779/A20097

Exploring the Experiential Journey of Women with PCOS Across the Lifespan: A Qualitative Inquiry

Pamela J Wright, Robin M Dawson, Cynthia F Corbett Advancing Chronic Care Outcomes through Research and iNnovation (ACORN) Center, Department of Biobehavioral Health & Nursing Science, College of Nursing, University of South Carolina, Columbia, SC, USACorrespondence: Pamela J Wright, Department of Biobehavioral Health & Nursing Science, College of Nursing, University of South Carolina, 1601 Greene Street, Columbia, SC, 29208, USA, Tel +1-803-777-6039, Email [email protected]: Peri-postmenopausal women with the chronic condition polycystic ovary syndrome (PCOS) remain at cardiometabolic risk and/or subsist with established comorbidity while continuing to manage persistent PCOS signs and symptoms, such as hirsutism. Thus, PCOS transcends the reproductive years, yet there is sparse scientific literature on the peri-postmenopausal years of women with PCOS.Purpose: To explore how peri-postmenopausal women’s perceptions about PCOS have changed over the lifespan since their PCOS diagnosis.Methods: A cross-sectional survey with one qualitative question was conducted via Research Electronic Data Capture (REDCap) among women with PCOS aged ≥ 43 years, who were all recruited from PCOS-specific Facebook pages. Of the 107 women completing the survey, 72 substantively answered the qualitative question. The qualitative responses were analyzed using the steps of reflexive thematic analysis. Themes were interpreted and discussed through the lens of the bioecological conceptual model.Results: Respondents were 47.6 (± 4.1) years of age, primarily White (87.5%), employed full time (65.3%), and married (75%) with children (68%). Four overall themes were identified: 1) dismissal 2) information desert, 3) PCOS experience over the lifespan, and 4) mindset.Conclusion: The study findings illustrated the unique healthcare needs among peri-postmenopausal women with PCOS. Further research is needed to further explore their healthcare concerns and psychosocial needs followed by studies that develop and assess interventions that promote symptom and adaptive coping strategies across their lifespan.Keywords: polycystic ovary syndrome, systems theory, life course, women’s healt

On the methodological unification in electroencephalography

BACKGROUND: This paper presents results of a pursuit of a repeatable and objective methodology of analysis of the electroencephalographic (EEG) time series. METHODS: Adaptive time-frequency approximations of EEG are discussed in the light of the available experimental and theoretical evidence, and applicability in various experimental and clinical setups. RESULTS: Four lemmas and three conjectures support the following conclusion. CONCLUSION: Adaptive time-frequency approximations of signals unify most of the univariate computational approaches to EEG analysis, and offer compatibility with its traditional (visual) analysis, used in clinical applications

A Swift look at SN 2011fe: the earliest ultraviolet observations of a Type Ia supernova

We present the earliest ultraviolet (UV) observations of the bright Type Ia supernova SN 2011fe/PTF11kly in the nearby galaxy M101 at a distance of only 6.4 Mpc. It was discovered shortly after explosion by the Palomar Transient Factory and first observed by Swift/UVOT about a day after explosion. The early UV light is well defined, with ~20 data points per filter in the five days after explosion. These early and well-sampled UV observations form new template light curves for comparison with observations of other SNe Ia at low and high redshift. We report fits from semiempirical models of the explosion and find the time evolution of the early UV flux to be well fitted by the superposition of two parabolic curves. Finally, we use the early UV flux measurements to examine a possible shock interaction with a non-degenerate companion. From models predicting the measurable shock emission, we find that even a solar mass companion at a distance of a few solar radii is unlikely at more than 95% confidence

The "Artificial Mathematician" Objection: Exploring the (Im)possibility of Automating Mathematical Understanding

Reuben Hersh confided to us that, about forty years ago, the late Paul Cohen predicted to him that at some unspecified point in the future, mathematicians would be replaced by computers. Rather than focus on computers replacing mathematicians, however, our aim is to consider the (im)possibility of human mathematicians being joined by “artificial mathematicians” in the proving practice—not just as a method of inquiry but as a fellow inquirer

A comparison of missing data methods for hypothesis tests of the treatment effect in substance abuse clinical trials: a Monte-Carlo simulation study

<p>Abstract</p> <p>Background</p> <p>Missing data due to attrition are rampant in substance abuse clinical trials. However, missing data are often ignored in the presentation of substance abuse clinical trials. This paper demonstrates missing data methods which may be used for hypothesis testing.</p> <p>Methods</p> <p>Methods involving stratifying and weighting individuals based on missing data pattern are shown to produce tests that are robust to missing data mechanisms in terms of Type I error and power. In this article, we describe several methods of combining data that may be used for testing hypotheses of the treatment effect. Furthermore, illustrations of each test's Type I error and power under different missing data percentages and mechanisms are quantified using a Monte-Carlo simulation study.</p> <p>Results</p> <p>Type I error rates were similar for each method, while powers depended on missing data assumptions. Specifically, power was greatest for the weighted, compared to un-weighted methods, especially for greater missing data percentages.</p> <p>Conclusion</p> <p>Results of this study as well as extant literature demonstrate the need for standards of design and analysis specific to substance abuse clinical trials. Given the known substantial attrition rates and concern for the missing data mechanism in substance abuse clinical trials, investigators need to incorporate missing data methods a priori. That is, missing data methods should be specified at the outset of the study and not after the data have been collected.</p