Establishing and transducing cell polarity: common themes and variations

All cells in vivo have a primary axis of polarity that controls many aspects of their behaviour, such as the direction of protein secretion and signalling, the orientation of cell division and directed cell movement and morphogenesis. Cell polarise in response to extracellular cues or intracellular landmarks that initiate a signal transduction process that establishes complementary cortical domains of conserved polarity factors. These cortical domains then transmit this polarity to the rest of the cell by regulating the organisation of the cytoskeleton and membrane trafficking systems. Here I review work over the past couple of years that has elucidated many key features of how polarity is established and transduced in different systems, but has also revealed unexpected variations in polarity mechanisms depending on context.I am supported by Wellcome Principal Research Fellowship 080007/B/06/Z

A Distinguished Vacuum State for a Quantum Field in a Curved Spacetime: Formalism, Features, and Cosmology

We define a distinguished "ground state" or "vacuum" for a free scalar quantum field in a globally hyperbolic region of an arbitrarily curved spacetime. Our prescription is motivated by the recent construction of a quantum field theory on a background causal set using only knowledge of the retarded Green's function. We generalize that construction to continuum spacetimes and find that it yields a distinguished vacuum or ground state for a non-interacting, massive or massless scalar field. This state is defined for all compact regions and for many noncompact ones. In a static spacetime we find that our vacuum coincides with the usual ground state. We determine it also for a radiation-filled, spatially homogeneous and isotropic cosmos, and show that the super-horizon correlations are approximately the same as those of a thermal state. Finally, we illustrate the inherent non-locality of our prescription with the example of a spacetime which sandwiches a region with curvature in-between flat initial and final regions

Quantitative susceptibility mapping of carotid arterial tissue ex vivo: Assessing sensitivity to vessel microstructural composition

PURPOSE: To characterize microstructural contributions to the magnetic susceptibility of carotid arteries. METHOD: Arterial vessels were scanned using high-resolution quantitative susceptibility mapping (QSM) at 7 Tesla. Models of vessel degradation were generated using ex vivo porcine carotid arteries that were subjected to several different enzymatic digestion treatments that selectively removed microstructural components (smooth muscle cells, collagen, and elastin). Magnetic susceptibilities measured in these tissue models were compared to those in untreated (native) porcine arteries. Magnetic susceptibility measured in native porcine carotid arteries was further compared to the susceptibility of cadaveric human carotid arteries to investigate their similarity. RESULTS: The magnetic susceptibility of native porcine vessels was diamagnetic (χnative = -0.1820 ppm), with higher susceptibilities in all models of vessel degradation (χelastin-degraded = -0.0163 ppm; χcollagen-degraded = -0.1158 ppm; χdecellularized = -0.1379 ppm; χfixed native = -0.2199 ppm). Magnetic susceptibility was significantly higher in collagen-degraded compared to native porcine vessels (Tukey-Kramer, P .05). CONCLUSIONS: Magnetic susceptibility measured using QSM is sensitive to the microstructural composition of arterial vessels-most notably to collagen. The similarity of human and porcine arterial tissue susceptibility values provides a solid basis for translational studies. Because vessel microstructure becomes disrupted during the onset and progression of carotid atherosclerosis, QSM has the potential to provide a sensitive and specific marker of vessel disease

Biofeedback for treatment of irritable bowel syndrome.

BACKGROUND:Irritable bowel syndrome (IBS) is a prevalent condition that currently lacks highly effective therapies for its management. Biofeedback has been proposed as a therapy that may help individuals learn to exert conscious control over sympatho-vagal balance as an indirect method of symptom management. OBJECTIVES:Our primary objective was to assess the efficacy and safety of biofeedback-based interventions for IBS in adults and children. SEARCH METHODS:We searched the Cochrane Inflammatory Bowel Disease (IBD) Group Specialized Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Allied and Complementary Medicine Database (AMED) from inception to 24 July 2019. We also searched reference lists from published trials, trial registries, device manufacturers, conference proceedings, theses, and dissertations. SELECTION CRITERIA:We judged randomized controlled trials to be eligible for inclusion if they met the Association for Applied Psychophysiology and Biofeedback definition of biofeedback, and if they compared a biofeedback intervention to an active, sham, or no-treatment control for the management of IBS. DATA COLLECTION AND ANALYSIS:Two authors independently screened trials for inclusion, extracted data, and assessed risk of bias. Primary outcomes were IBS global or clinical improvement scores and overall quality of life measures. Secondary outcome measures were adverse events, assessments of stool frequency and consistency, changes in abdominal pain, depression, and anxiety. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI). For continuous outcomes, we calculated the mean difference (MD) and 95% CI. We used GRADE criteria to assess the overall certainty of the evidence. MAIN RESULTS:We identified eight randomized trials with a total of 300 adult participants for our analysis. We did not identify any trials in children. Four trials assessed thermal biofeedback. One trial assessed rectosigmoidal biofeedback. Two trials assessed heart rate variability biofeedback. Two trials assessed electrocutaneous biofeedback. Comparators were: no treatment (symptom monitoring group; three studies), attention control (pseudomeditation; two studies), relaxation control (one study), counseling (two studies), hypnotherapy (one study), standard therapy (one study), and sham biofeedback (one study). We judged all trials to have a high or unclear risk of bias. Global/Clinical improvement The clinical benefit of biofeedback plus standard therapy compared to standard therapy alone was uncertain (RR 4.20, 95% CI 1.40 to 12.58; 1 study, 20 participants; very low-certainty evidence). The same study also compared biofeedback plus standard therapy to sham biofeedback plus standard therapy. The clinical benefit in the biofeedback group was uncertain (RR 2.33, 95% CI 1.13 to 4.80; 1 study, 20 participants; very low-certainty evidence). The clinical benefit of heart rate biofeedback compared to hypnotherapy was uncertain when measured with the IBS severity scoring system (IBS-SSS) (MD -58.80, 95% CI -109.11 to -8.49; 1 study, 61 participants; low-certainty evidence). Compared to counseling, the effect of heart rate biofeedback was unclear when measured with a composite symptom reduction score (MD 7.03, 95% CI -51.07 to 65.13; 1 study, 29 participants; low-certainty evidence) and when evaluated for clinical response (50% improvement) (RR 1.09, 95% CI 0.48 to 2.45; 1 study, 29 participants; low-certainty evidence). The clinical benefit of thermal biofeedback used in a multi-component psychological intervention (MCPI) compared to no treatment was uncertain when measured with a composite clinical symptom reduction score (MD 30.34, 95% CI 8.47 to 52.21; 3 studies, 101 participants; very low-certainty evidence), and when evaluated as clinical response (50% improvement) (RR 2.12, 95% CI 1.24 to 3.62; 3 studies, 101 participants; very low-certainty evidence). Compared to attention control, the effects of thermal biofeedback within an MCPI were unclear when measured with a composite clinical symptom reduction score (MD 4.02, 95% CI -21.41 to 29.45; 2 studies, 80 participants; very low-certainty evidence) and when evaluated as clinical response (50% improvement) (RR 1.10, 95% CI 0.72 to 1.69, 2 studies, 80 participants; very low-certainty evidence). Quality of life A single trial used overall quality of life as an outcome measure, and reported that both the biofeedback and cognitive therapy groups improved after treatment. The trial did not note any between-group differences, and did not report any outcome data. Adverse events Only one of the eight trials explicitly reported adverse events. This study reported no adverse events in either the biofeedback or cognitive therapy groups (RD 0.00, 95% CI -0.12 to 0.12; 29 participants; low-certainty evidence). AUTHORS' CONCLUSIONS:There is currently not enough evidence to assess whether biofeedback interventions are effective for controlling symptoms of IBS. Given the positive results reported in small trials to date, biofeedback deserves further study in people with IBS. Future research should include active control groups that use high provider-participant interaction, in an attempt to balance non-specific effects of interventions between groups, and report both commonly used outcome measures (e.g. IBS-SSS) and historical outcome measures (e.g. the composite primary symptom reduction (CPSR) score) to allow for meta-analysis with previous studies. Future studies should be explicit in their reporting of adverse events

Performance analysis of single board computer clusters

The past few years have seen significant developments in Single Board Computer (SBC) hardware capabilities. These advances in SBCs translate directly into improvements in SBC clusters. In 2018 an individual SBC has more than four times the performance of a 64-node SBC cluster from 2013. This increase in performance has been accompanied by increases in energy efficiency (GFLOPS/W) and value for money (GFLOPS/$). We present systematic analysis of these metrics for three different SBC clusters composed of Raspberry Pi 3 Model B, Raspberry Pi 3 Model B+ and Odroid C2 nodes respectively. A 16-node SBC cluster can achieve up to 60GFLOPS, running at 80W. We believe that these improvements open new computational opportunities, whether this derives from a decrease in the physical volume required to provide a fixed amount of computation power for a portable cluster; or the amount of compute power that can be installed given a fixed budget in expendable compute scenarios. We also present a new SBC cluster construction form factor named Pi Stack; this has been designed to support edge compute applications rather than the educational use-cases favoured by previous methods. The improvements in SBC cluster performance and construction techniques mean that these SBC clusters are realising their potential as valuable developmental edge compute devices rather than just educational curiosities

The validity of raw custom-processed global navigation satellite systems data during straight-line sprinting across multiple days

Objectives: (1) Determine the validity of instantaneous speed and acceleration and (2) the variation in validity over time (multiple sessions) for global navigation satellite systems (GNSS) devices. Design: Repeated measures. Methods: 10-Hz GNSS devices from Statsports (n = 2, Apex Pro) and Catapult (n = 2, Vector S7) were examined, whilst a speed laser manufactured by MuscleLab (n = 1, LaserSpeed) was the criterion measure, sampling at 2.56 kHz, with data exported at 1000 Hz. Ten participants completed 40 m sprinting and changes of pace on three separate days. Root mean square error (RMSE) was used to assess the magnitude and direction of the difference between GNSS and criterion measures (instantaneous speed, instantaneous acceleration). Linear mixed models were built to assess the difference in validity across days. Results: RMSE ranged from 0.14 to 0.21 m·s−1 and 0.22 to 0.47 m·s−2 for speed and acceleration, respectively showing strong agreement. There were small variations in the agreement to criterion between days for both devices for speed (Catapult RMSE = 0.12 to 21 m·s−1; Statsports RMSE = 0.14 to 0.17 m·s−1) and for acceleration (Catapult RMSE = 0.26 to 0.47 m·s−2; Statsports RMSE = 0.22 to 0.43 m·s−2) across all movements. There was a negative linear relationship between speed and acceleration error as speed increased. Conclusions: Wearable microtechnology devices from Catapult (Vector S7) and Statsports (Apex Pro) have suitable validity when measuring instantaneous speed and acceleration across multiple days. There may be small variations during different sessions and over the speed spectrum