LOFAR early-time search for coherent radio emission from GRB 180706A

© 2019 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society.The nature of the central engines of gamma-ray bursts (GRBs) and the composition of their relativistic jets are still under debate. If the jets are Poynting flux dominated rather than baryon dominated, a coherent radio flare from magnetic re-connection events might be expected with the prompt gamma-ray emission. There are two competing models for the central engines of GRBs; a black hole or a newly formed milli-second magnetar. If the central engine is a magnetar it is predicted to produce coherent radio emission as persistent or flaring activity. In this paper, we present the deepest limits to date for this emission following LOFAR rapid response observations of GRB 180706A. No emission is detected to a 3$\sigma$ limit of 1.7 mJy beam$^{-1}$ at 144 MHz in a two-hour LOFAR observation starting 4.5 minutes after the gamma-ray trigger. A forced source extraction at the position of GRB 180706A provides a marginally positive (1 sigma) peak flux density of $1.1 \pm 0.9$ mJy. The data were time-sliced into different sets of snapshot durations to search for FRB like emission. No short duration emission was detected at the location of the GRB. We compare these results to theoretical models and discuss the implications of a non-detection.Peer reviewedFinal Accepted Versio

Cognitive and attitudinal impacts of a university AIDS course: interdisciplinary education as a public health intervention.

This paper describes an interdisciplinary, variable credit-bearing university course on acquired immunodeficiency syndrome (AIDS) that enrolled 429 students. Pre- and post-course questionnaries were used to assess knowledge and attitudes relative to AIDS and these were compared to National Health Interview Survey findings. Considerable cognitive and attitudinal changes occurred over the course period. University courses, taught annually, were found to be an efficient mechanism for educating large numbers of future community leaders and professionals about AID

Case finding of mild cognitive impairment and dementia and subsequent care; results of a cluster RCT in primary care

Purpose Despite a call for earlier diagnosis of dementia, the diagnostic yield of case finding and its impact on the mental health of patients and relatives are unclear. This study assessed the effect of a two-component intervention of case finding and subsequent care on these outcomes. Methods In a cluster RCT we assessed whether education of family physicians (FPs; trial stage 1) resulted in more mild cognitive impairment (MCI) and dementia diagnoses among older persons in whom FPs suspected cognitive decline and whether case finding by a practice nurse and the FP (trial stage 2) added to this number of diagnoses. In addition, we assessed mental health effects of case finding and subsequent care (trial stage 2). FPs of 15 primary care practices (PCPs = clusters) judged the cognitive status of all persons ≤ 65 years. The primary outcome, new MCI and dementia diagnoses by FPs after 12 months as indicated on a list, was assessed among all persons in whom FPs suspected cognitive impairment but without a formal diagnosis of dementia. The secondary outcome, mental health of patients and their relatives, was assessed among persons consenting to participate in trial stage 2. Trial stage 1 consisted of either intervention component 1: training FPs to diagnose MCI and dementia, or control: no training. Trial stage 2 consisted of either intervention component 2: case finding of MCI and dementia and care by a trained nurse and the FP, or control: care as usual. Results Seven PCPs were randomized to the intervention; eight to the control condition. MCI or dementia was diagnosed in 42.3 (138/326) of persons in the intervention, and in 30.5 (98/321) in the control group (estimated difference GEE: 10.8, OR: 1.51, 95-CI 0.60-3.76). Among patients and relatives who consented to stage 2 of the trial (n = 145; 25), there were no differences in mental health between the intervention and control group. Conclusions We found a non-significant increase in the number of new MCI diagnoses. As we cannot exclude a clinically relevant effect, a larger study is warranted to replicate ours. Trial Registration Nederlands Trial Register NTR3389 © 2016 van den Dungen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Constraining Radio Emission from Magnetars

We report on radio observations of five magnetars and two magnetar candidates carried out at 1950 MHz with the Green Bank Telescope in 2006-2007. The data from these observations were searched for periodic emission and bright single pulses. Also, monitoring observations of magnetar 4U0142+61 following its 2006 X-ray bursts were obtained. No radio emission was detected was detected for any of our targets. The non-detections allow us to place luminosity upper limits (at 1950 MHz) of approximately L < 1.60 mJy kpc^2 for periodic emission and L < 7.6 Jy kpc^2 for single pulse emission. These are the most stringent limits yet for the magnetars observed. The resulting luminosity upper limits together with previous results are discussed, as is the importance of further radio observations of radio-loud and radio-quiet magnetars.Comment: 11 pages, 4 figure

Prognosis and Survival of Older Patients With Dizziness in Primary Care:a 10-year prospective cohort study

Purpose: The prognosis of dizzy older patients in primary care is unknown. Our objective was to determine the prognosis and survival of patients with different subtypes and causes of dizziness. Methods: In a primary care prospective cohort study, 417 older adults with dizziness (mean age 75.5 years) received a full diagnostic workup in 2006-2008. A panel of physicians classified their dizziness subtype and primary cause of dizziness. Presyncope was the most common dizziness subtype (69.1%), followed by vertigo (41.0%), disequilibrium (39.8%), and other dizziness (1.7%). The most common primary causes of dizziness were cardiovascular disease (56.8%) and peripheral vestibular disease (14.4%). Main outcome measures were mortality and dizziness-related impairment assessed at 10-year follow-up.Results: At 10-year follow-up 169 patients (40.5%) had died. Multivariable adjusted Cox models showed a lower mortality rate for patients with the subtype vertigo compared to other subtypes (HR 0.62 (95% CI 0.40 to 0.96)), and for peripheral vestibular disease versus cardiovascular disease as primary cause of dizziness (HR 0.46 (95% CI 0.25 to 0.84)). After 10 years, 47.7% of patients who filled out the follow-up measurement experienced substantial dizziness-related impairment. No significant difference in substantial impairment was seen between different subtypes and primary causes of dizziness. Conclusions: The 10-year mortality rate was lower for the dizziness subtype vertigo compared to other subtypes. Patients with dizziness primarily caused by peripheral vestibular disease had a lower mortality rate than patients with cardiovascular disease. Substantial dizziness-related impairment in older dizzy patients 10 years later is high, and indicates that current treatment strategies by FPs may be suboptimal.<br/

A novel chemogenomics analysis of G protein-coupled receptors (GPCRs) and their ligands: a potential strategy for receptor de-orphanization.

BACKGROUND: G protein-coupled receptors (GPCRs) represent a family of well-characterized drug targets with significant therapeutic value. Phylogenetic classifications may help to understand the characteristics of individual GPCRs and their subtypes. Previous phylogenetic classifications were all based on the sequences of receptors, adding only minor information about the ligand binding properties of the receptors. In this work, we compare a sequence-based classification of receptors to a ligand-based classification of the same group of receptors, and evaluate the potential to use sequence relatedness as a predictor for ligand interactions thus aiding the quest for ligands of orphan receptors. RESULTS: We present a classification of GPCRs that is purely based on their ligands, complementing sequence-based phylogenetic classifications of these receptors. Targets were hierarchically classified into phylogenetic trees, for both sequence space and ligand (substructure) space. The overall organization of the sequence-based tree and substructure-based tree was similar; in particular, the adenosine receptors cluster together as well as most peptide receptor subtypes (e.g. opioid, somatostatin) and adrenoceptor subtypes. In ligand space, the prostanoid and cannabinoid receptors are more distant from the other targets, whereas the tachykinin receptors, the oxytocin receptor, and serotonin receptors are closer to the other targets, which is indicative for ligand promiscuity. In 93% of the receptors studied, de-orphanization of a simulated orphan receptor using the ligands of related receptors performed better than random (AUC > 0.5) and for 35% of receptors de-orphanization performance was good (AUC > 0.7). CONCLUSIONS: We constructed a phylogenetic classification of GPCRs that is solely based on the ligands of these receptors. The similarities and differences with traditional sequence-based classifications were investigated: our ligand-based classification uncovers relationships among GPCRs that are not apparent from the sequence-based classification. This will shed light on potential cross-reactivity of GPCR ligands and will aid the design of new ligands with the desired activity profiles. In addition, we linked the ligand-based classification with a ligand-focused sequence-based classification described in literature and proved the potential of this method for de-orphanization of GPCRs.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Radiologic Characteristics of Spinal Hemangioblastomas in von Hippel Lindau Disease as Guidance in Clinical Interventions

Objective: Hemangioblastomas in the central nervous system are the most common manifestation of von Hippel-Lindau (VHL) disease. Because the growth rate of hemangioblastomas is unpredictable, regular follow-up is mandatory, focusing on clinical symptoms and imaging of the central nervous system. However, clinical symptoms may be subtle and nonspecific, and data about the relationship between the radiologic findings and clinical symptoms are sparse. This study aims to evaluate if and how findings of magnetic resonance imaging (MRI) regarding spinal hemangioblastomas are associated with symptoms of VHL disease, with special attention to peritumoral edema and spinal cysts. Methods: Serial spinal MRI scans of 43 genetically or clinically established VHL patients with at least 2 years of follow-up were reevaluated to examine the volume, growth rate, and location of spinal hemangioblastomas and the presence, size, and growth rate of peritumoral edema and cysts. Findings were compared with clinical symptoms using the Fisher exact test. Results: We observed a total of 77 spinal hemangioblastomas in 28 patients. Eight of the 28 patients showed peritumoral edema and spinal cysts, and 1 patient showed peritumoral edema without cyst formation; 6 of these 9 patients showed clinical symptoms. Both peritumoral edema and spinal cysts were associated with clinical symptoms (P = 0.023 and P = 0.011, respectively). Conclusions: The presence of peritumoral edema and/or spinal cysts shown on MRI in VHL patients with spinal hemangioblastomas is associated with symptoms in more than half of the patients and may alert the clinician to intensify clinical and radiologic surveillance.</p

Hypocalcemia induced by tyrosine kinase inhibitors:targeted treatment with 'untargeted' side effects

Experimentele farmacotherapi

Ab-initio prediction of the electronic and optical excitations in polythiophene: isolated chains versus bulk polymer

We calculate the electronic and optical excitations of polythiophene using the GW approximation for the electronic self-energy, and include excitonic effects by solving the electron-hole Bethe-Salpeter equation. Two different situations are studied: excitations on isolated chains and excitations on chains in crystalline polythiophene. The dielectric tensor for the crystalline situation is obtained by modeling the polymer chains as polarizable line objects, with a long-wavelength polarizability tensor obtained from the ab-initio polarizability function of the isolated chain. With this model dielectric tensor we construct a screened interaction for the crystalline case, including both intra- and interchain screening. In the crystalline situation both the quasi-particle band gap and the exciton binding energies are drastically reduced in comparison with the isolated chain. However, the optical gap is hardly affected. We expect this result to be relevant for conjugated polymers in general.Comment: 15 pages including 4 figures; to appear in Phys. Rev. B, 6/15/200

Evolutionary Multi-Objective Design of SARS-CoV-2 Protease Inhibitor Candidates

Computational drug design based on artificial intelligence is an emerging research area. At the time of writing this paper, the world suffers from an outbreak of the coronavirus SARS-CoV-2. A promising way to stop the virus replication is via protease inhibition. We propose an evolutionary multi-objective algorithm (EMOA) to design potential protease inhibitors for SARS-CoV-2's main protease. Based on the SELFIES representation the EMOA maximizes the binding of candidate ligands to the protein using the docking tool QuickVina 2, while at the same time taking into account further objectives like drug-likeliness or the fulfillment of filter constraints. The experimental part analyzes the evolutionary process and discusses the inhibitor candidates.Comment: 15 pages, 7 figures, submitted to PPSN 202