Modelling the photopolarimetric variability of AA Tau

We present Monte Carlo scattered light models of a warped disc that reproduce the observed photopolarimetric variability of the classical T Tauri star, AA Tauri. For a system inclination of 75° and using an analytic description for a warped inner disc, we find that the shape and amplitude of the photopolarimetric variability are reproduced with a warp that occults the star, located at 0.07 au, amplitude 0.016 au, extending over radial and azimuthal ranges 0.0084 au and 145°. We also show a time sequence of high spatial resolution scattered light images, showing a dark shadow cast by the warp sweeping round the disc. Using a modified smooth particle hydrodynamics code, we find that a stellar dipole magnetic field of strength 5.2 kG, inclined at 30° to the stellar rotation axis can reproduce the required disc warping to explain the photopolarimetric variability of AA Ta

Remote effects of acute kidney injury in a porcine model

Background: Acute Kidney Injury (AKI) is a common and serious disease with no specific treatment. An episode of AKI may affect organs distant to the kidney, further increasing the morbidity associated with AKI. The mechanism of organ cross-talk after AKI is unclear. The renal and immune systems of pigs and humans are alike. Using a preclinical animal (porcine) model, we test the hypothesis that early effects of AKI on distant organs is by immune cell infiltration leading to inflammatory cytokine production, extravasation and edema. Study Design: In 29 pigs exposed to either sham-surgery or renal ischemia-reperfusion (control, n=12; AKI, n=17) we assessed remote organ (liver, lung, brain) effects in the short-(from 2 to 48h reperfusion) and longer-term (5 weeks later) using immunofluorescence (for leucocyte infiltration, apoptosis), a cytokine array, tissue elemental analysis (electrolytes), blood hematology and chemistry (e.g. liver enzymes) and PCR (for inflammatory markers). Results: AKI elicited significant, short-term (~24h) increments in enzymes indicative of acute liver damage (e.g. AST:ALT ratio; P=0.02) and influenced tissue biochemistry in some remote organs (e.g. lung tissue [Ca++] increased; P=0.04). These effects largely resolved after 48h and no further histopathology, edema, apoptosis or immune cell infiltration was noted in liver, lung or hippocampus in the short- and longer-term. Conclusions: AKI has subtle biochemical effects on remote organs in the short-term including a transient increment in markers of acute liver damage. These effects resolved by 48h and no further remote organ histopathology, apoptosis, edema or immune cell infiltration was noted

The Promotion of ‘Grab Bags’ as a Disaster Risk Reduction Strategy.

Introduction: An all-of-society approach to disaster risk reduction emphasizes inclusion and engagement in preparedness activities. A common recommendation is to promote household preparedness through the preparation of a ‘grab bag’ or ‘disaster kit’, that can be used to shelter-in-place or evacuate. However, there are knowledge gaps related to how this strategy is being used around the world as a disaster risk reduction strategy, and what evidence there is to support recommendations. Methods: In this paper, we present an exploratory study undertaken to provide insight into how grab bag guidelines are used to promote preparedness in Canada, China, England, Japan, and Scotland, and supplemented by a literature review to understand existing evidence for this strategy. Results: There are gaps in the literature regarding evidence on grab bag effectiveness. We also found variations in how grab bag guidelines are promoted across the five case studies. Discussion: While there are clearly common items recommended for household grab bags (such as water and first aid kits), there are gaps in the literature regarding: 1) the evidence base to inform guidelines; 2) uptake of guidelines; and 3) to what extent grab bags reduce demands on essential services and improve disaster resilience

Challenges of developing robust AI for intrapartum fetal heart rate monitoring

Background: CTG remains the only non-invasive tool available to the maternity team for continuous monitoring of fetal well-being during labour. Despite widespread use and investment in staff training, difficulty with CTG interpretation continues to be identified as a problem in cases of fetal hypoxia, which often results in permanent brain injury. Given the recent advances in AI, it is hoped that its application to CTG will offer a better, less subjective and more reliable method of CTG interpretation. Objectives: This mini-review examines the literature and discusses the impediments to the success of AI application to CTG thus far. Prior randomised control trials (RCTs) of CTG decision support systems are reviewed from technical and clinical perspectives. A selection of novel engineering approaches, not yet validated in RCTs, are also reviewed. The review presents the key challenges that need to be addressed in order to develop a robust AI tool to identify fetal distress in a timely manner so that appropriate intervention can be made. Results: The decision support systems used in three RCTs were reviewed, summarising the algorithms, the outcomes of the trials and the limitations. Preliminary work suggests that the inclusion of clinical data can improve the performance of AI-assisted CTG. Combined with newer approaches to the classification of traces, this offers promise for rewarding future development

A sense of embodiment is reflected in people's signature size

BACKGROUND: The size of a person's signature may reveal implicit information about how the self is perceived although this has not been closely examined. METHODS/RESULTS: We conducted three experiments to test whether increases in signature size can be induced. Specifically, the aim of these experiments was to test whether changes in signature size reflect a person's current implicit sense of embodiment. Experiment 1 showed that an implicit affect task (positive subliminal evaluative conditioning) led to increases in signature size relative to an affectively neutral task, showing that implicit affective cues alter signature size. Experiments 2 and 3 demonstrated increases in signature size following experiential self-focus on sensory and affective stimuli relative to both conceptual self-focus and external (non-self-focus) in both healthy participants and patients with anorexia nervosa, a disorder associated with self-evaluation and a sense of disembodiment. In all three experiments, increases in signature size were unrelated to changes in self-reported mood and larger than manipulation unrelated variations. CONCLUSIONS: Together, these findings suggest that a person's sense of embodiment is reflected in their signature size

Multifocal demyelinating motor neuropathy and hamartoma syndrome associated with a de novo PTEN mutation.

OBJECTIVE: To describe a patient with a multifocal demyelinating motor neuropathy with onset in childhood and a mutation in phosphatase and tensin homolog (PTEN), a tumor suppressor gene associated with inherited tumor susceptibility conditions, macrocephaly, autism, ataxia, tremor, and epilepsy. Functional implications of this protein have been investigated in Parkinson and Alzheimer diseases. METHODS: We performed whole-exome sequencing in the patient's genomic DNA validated by Sanger sequencing. Immunoblotting, in vitro enzymatic assay, and label-free shotgun proteomic profiling were performed in the patient's fibroblasts. RESULTS: The predominant clinical presentation of the patient was a childhood onset, asymmetric progressive multifocal motor neuropathy. In addition, he presented with macrocephaly, autism spectrum disorder, and skin hamartomas, considered as clinical criteria for PTEN-related hamartoma tumor syndrome. Extensive tumor screening did not detect any malignancies. We detected a novel de novo heterozygous c.269T>C, p.(Phe90Ser) PTEN variant, which was absent in both parents. The pathogenicity of the variant is supported by altered expression of several PTEN-associated proteins involved in tumorigenesis. Moreover, fibroblasts showed a defect in catalytic activity of PTEN against the secondary substrate, phosphatidylinositol 3,4-trisphosphate. In support of our findings, focal hypermyelination leading to peripheral neuropathy has been reported in PTEN-deficient mice. CONCLUSION: We describe a novel phenotype, PTEN-associated multifocal demyelinating motor neuropathy with a skin hamartoma syndrome. A similar mechanism may potentially underlie other forms of Charcot-Marie-Tooth disease with involvement of the phosphatidylinositol pathway

Gemini/GMOS Imaging of Globular Cluster Systems in Five Early-type Galaxies

This paper presents deep high quality photometry of globular cluster (GC) systems belonging to five early-type galaxies covering a range of mass and environment. Photometric data were obtained with the Gemini North and Gemini South telescopes in the filter passbands g', r', and i'. The combination of these filters with good seeing conditions allows an excellent separation between GC candidates and unresolved field objects. Bimodal GC colour distributions are found in all five galaxies. Most of the GC systems appear bimodal even in the (g' -r') vs (r' -i') plane. A population of resolved/marginally resolved GC and Ultra Compact Dwarf candidates was found in all the galaxies. A search for the so-called "blue tilt" in the colour-magnitude diagrams reveals that NGC 4649 clearly shows that phenomenon although no conclusive evidence was found for the other galaxies in the sample. This "blue tilt" translates into a mass-metallicity relation given by Z \propto M^0.28\pm0.03 . This dependence was found using a new empirical (g' -i') vs [Z/H] relation which relies on an homogeneous sample of GC colours and metallicities. This paper also explores the radial trends in both colour and surface density for the blue (metal-poor) and red (metal-rich) GC subpopulations. As usual, the red GCs show a steeper radial distribution than the blue ones. Evidence of galactocentric colour gradients is found in some of the GC systems, being more significant for the two S0 galaxies in the sample. Red GC subpopulations show similar colours and gradients to the galaxy halo stars in their inner region. A GC mean colour-galaxy luminosity relation, consistent with [Z/H] \propto L_B ^0.26\pm0.08, is present for the red GCs. An estimate of the total GC populations and specific frequency SN values is presented for NGC 3115, NGC 3379, NGC 3923 and NGC 4649.Comment: 23 pages, 13 figures and 9 tables. Tables A1 and A2 will be published in full online only. Accepted for publication in MNRA

Convulsant Doses of a Dopamine D1 Receptor Agonist Result in Erk-Dependent Increases in Zif268 and Arc/Arg3.1 Expression in Mouse Dentate Gyrus

Activation of dopamine D1 receptors (D1Rs) has been shown to induce epileptiform activity. We studied the molecular changes occurring in the hippocampus in response to the administration of the D1-type receptor agonist, SKF 81297. SKF 81297 at 2.5 and 5.0 mg/kg induced behavioural seizures. Electrophysiological recordings in the dentate gyrus revealed the presence of epileptiform discharges peaking at 30–45 min post-injection and declining by 60 min. Seizures were prevented by the D1-type receptor antagonist, SCH 23390, or the cannabinoid CB1 receptor agonist, CP 55,940. The effect of SKF 81297 was accompanied by increased phosphorylation of the extracellular signal-regulated protein kinases 1 and 2 (ERK), in the granule cells of the dentate gyrus. This effect was also observed in response to administration of other D1-type receptor agonists, such as SKF83822 and SKF83959. In addition, SKF 81297 increased the phosphorylation of the ribosomal protein S6 and histone H3, two downstream targets of ERK. These effects were prevented by genetic inactivation of D1Rs, or by pharmacological inhibition of ERK. SKF 81297 was also able to enhance the levels of Zif268 and Arc/Arg3.1, two immediate early genes involved in transcriptional regulation and synaptic plasticity. These changes may be involved in forms of activity-dependent plasticity linked to the manifestation of seizures and to the ability of dopamine to affect learning and memory

Structural Requirements for Dihydrobenzoxazepinone Anthelmintics:Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni

Nine hundred million people are infected with the soil-transmitted helminths Ascaris lumbricoides (roundworm), hookworm, and Trichuris trichiura (whipworm). However, low single-dose cure rates of the benzimidazole drugs, the mainstay of preventative chemotherapy for whipworm, together with parasite drug resistance, mean that current approaches may not be able to eliminate morbidity from trichuriasis. We are seeking to develop new anthelmintic drugs specifically with activity against whipworm as a priority and previously identified a hit series of dihydrobenzoxazepinone (DHB) compounds that block motility of ex vivo Trichuris muris. Here, we report a systematic investigation of the structure–activity relationship of the anthelmintic activity of DHB compounds. We synthesized 47 analogues, which allowed us to define features of the molecules essential for anthelmintic action as well as broadening the chemotype by identification of dihydrobenzoquinolinones (DBQs) with anthelmintic activity. We investigated the activity of these compounds against other parasitic nematodes, identifying DHB compounds with activity against Brugia malayi and Heligmosomoides polygyrus. We also demonstrated activity of DHB compounds against the trematode Schistosoma mansoni, a parasite that causes schistosomiasis. These results demonstrate the potential of DHB and DBQ compounds for further development as broad-spectrum anthelmintics