Monitoring asthma in childhood : symptoms, exacerbations and quality of life

Acknowledgements The Task Force members and their affiliations are as follows. Paul L.P. Brand: Princess Amalia Children’s Centre, Isala Hospital, Zwolle, and UMCG Postgraduate School of Medicine, University Medical Centre and University of Groningen, Groningen, The Netherlands; Mika J. Mäkelä: Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland; Stanley J. Szefler: Children’s Hospital Colorado and University of Colorado Denver School of Medicine, Denver, CO, USA; Thomas Frischer: Dept of Paediatrics and Paediatric Surgery, Wilhelminenspital, Vienna, Austria; David Price: Dept of Primary Care Respiratory Medicine, Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; Eugenio Baraldi: Women’s and Children’s Health Dept, Unit of Respiratory Medicine and Allergy, University of Padova, Padova, Italy; Kai-Hakon Carlsen: Dept of Paediatrics, Women and Children’s Division, University of Oslo, and Oslo University Hospital, Oslo, Norway; Ernst Eber: Respiratory and Allergic Disease Division, Dept of Paediatrics and Adolescence Medicine, Medical University of Graz, Graz, Austria; Gunilla Hedlin: Dept of Women’s and Children’s Health and Centre for Allergy Research, Karolinska Institutet, and Astrid Lindgren Children’s hospital, Stockholm, Sweden; Neeta Kulkarni: Leicestershire Partnership Trust and Dept of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK; Christiane Lex: Dept of Paediatric Cardiology and Intensive Care Medicine, Division of Paediatric Respiratory Medicine, University Hospital Goettingen, Goettingen, Germany; Karin C. Lødrup Carlsen: Dept of Paediatrics, Women and Children’s Division, Oslo University Hospital, and Dept of Paediatrics, Faculty of Medicine, University of Oslo, Oslo, Norway; Eva Mantzouranis: Dept of Paediatrics, University Hospital of Heraklion, University of Crete, Heraklion, Greece; Alexander Moeller: Division of Respiratory Medicine, University Children’s Hospital Zurich, Zurich, Switzerland; Ian Pavord: Dept of Respiratory Medicine, University of Oxford, Oxford, UK; Giorgio Piacentini: Paediatric Section, Dept of Life and Reproduction Sciences, University of Verona, Verona, Italy; Mariëlle W. Pijnenburg: Dept Paediatrics/Paediatric Respiratory Medicine, Erasmus MC - Sophia Children’s Hospital, Rotterdam, The Netherlands; Bart L. Rottier: Dept of Pediatric Pulmonology and Allergology, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Sejal Saglani: Leukocyte Biology and Respiratory Paediatrics, National Heart and Lung Institute, Imperial College London, London, UK; Peter D. Sly: Queensland Children’s Medical Research Institute, The University of Queensland, Brisbane, Australia; Steve Turner: Dept of Paediatrics, University of Aberdeen, Aberdeen, UK; Edwina Wooler: Royal Alexandra Children’s Hospital, Brighton, UK.Peer reviewedPublisher PD

Training, status and migration of general practitioners / family physicians within Europe

The survey intended to explore and identify the training background and status of general practitioners/ family physicians (GPs) in member countries within EURACT (European Academy of Teachers in General Practice/Family Medicine), and to gain an overview of processes involved when GP-trained doctors migrate to work in another member country. A questionnaire, with closed and open-ended questions, was sent to representatives of all 39 EURACT-member countries in 2009. The main outcome measures were the training background and status of GPs in public/private settings in each country and the requirements of additional training and testing when migrating to another country. Forty-one completed questionnaires were received from 31 (79%) of the EURACT countries. The data indicate that specialist training for General Practice/ Family Medicine (GP/FM) is well established throughout and generally required for appointment to public career posts. The data also indicate that European Uniontrained GPs can move freely to most countries with usually no tests of medical knowledge or language proficiency. Orientation to the healthcare system in the destination country is usually not provided. work in public/private GP/FM posts in many European countries, although new appointments to public posts RESEARCH ARTICLE Training, status and migration of General Practitioners/Family Physicians within Europe in nearly all countries require specialist GP training. It was not possible to identify a uniform or agreed approach applied by employing agencies to confirm the medical competence and language skills of migrant doctors and to provide them with orientation to healthcare systems. In the high-context dependent discipline of GP/FM this is of concern.peer-reviewe

Cholestenoic acid, an endogenous cholesterol metabolite, is a potent γ-secretase modulator.

BackgroundAmyloid-β (Aβ) 42 has been implicated as the initiating molecule in the pathogenesis of Alzheimer's disease (AD); thus, therapeutic strategies that target Aβ42 are of great interest. γ-Secretase modulators (GSMs) are small molecules that selectively decrease Aβ42. We have previously reported that many acidic steroids are GSMs with potencies ranging in the low to mid micromolar concentration with 5β-cholanic acid being the most potent steroid identified GSM with half maximal effective concentration (EC50) of 5.7 μM.ResultsWe find that the endogenous cholesterol metabolite, 3β-hydroxy-5-cholestenoic acid (CA), is a steroid GSM with enhanced potency (EC50 of 250 nM) relative to 5β-cholanic acid. CA i) is found in human plasma at ~100-300 nM concentrations ii) has the typical acidic GSM signature of decreasing Aβ42 and increasing Aβ38 levels iii) is active in in vitro γ-secretase assay iv) is made in the brain. To test if CA acts as an endogenous GSM, we used Cyp27a1 knockout (Cyp27a1-/-) and Cyp7b1 knockout (Cyp7b1-/-) mice to investigate if manipulation of cholesterol metabolism pathways relevant to CA formation would affect brain Aβ42 levels. Our data show that Cyp27a1-/- had increased brain Aβ42, whereas Cyp7b1-/- mice had decreased brain Aβ42 levels; however, peripheral dosing of up to 100 mg/kg CA did not affect brain Aβ levels. Structure-activity relationship (SAR) studies with multiple known and novel CA analogs studies failed to reveal CA analogs with increased potency.ConclusionThese data suggest that CA may act as an endogenous GSM within the brain. Although it is conceptually attractive to try and increase the levels of CA in the brain for prevention of AD, our data suggest that this will not be easily accomplished

The New Counter-Terrorism and Countering Violent Extremism: Speech Regulation, Private Companies and Free Expression

Panel discussion on counter-terrorism and violent extremism.https://larc.cardozo.yu.edu/flyers-2017-2018/1041/thumbnail.jp

Targeted and Genome-Scale Methylomics Reveals Gene Body Signatures in Human Cell Lines

Cytosine methylation, an epigenetic modification of DNA, is a target of growing interest for developing high throughput profiling technologies. Here we introduce two new, complementary techniques for cytosine methylation profiling utilizing next generation sequencing technology: bisulfite padlock probes (BSPPs) and methyl sensitive cut counting (MSCC). In the first method, we designed a set of ~10,000 BSPPs distributed over the ENCODE pilot project regions to take advantage of existing expression and chromatin immunoprecipitation data. We observed a pattern of low promoter methylation coupled with high gene body methylation in highly expressed genes. Using the second method, MSCC, we gathered genome-scale data for 1.4 million HpaII sites and confirmed that gene body methylation in highly expressed genes is a consistent phenomenon over the entire genome. Our observations highlight the usefulness of techniques which are not inherently or intentionally biased in favor of only profiling particular subsets like CpG islands or promoter regions

Ultrafaint Dwarf Galaxy Candidates in the M81 Group: Signatures of Group Accretion

The faint and ultrafaint dwarf galaxies in the Local Group form the observational bedrock upon which our understanding of small-scale cosmology rests. In order to understand whether this insight generalizes, it is imperative to use resolved-star techniques to discover similarly faint satellites in nearby galaxy groups. We describe our search for ultrafaint galaxies in the M81 group using deep ground-based resolved-star data sets from Subaru's Hyper Suprime-Cam. We present one new ultrafaint dwarf galaxy in the M81 group and identify five additional extremely low surface brightness candidate ultrafaint dwarfs that reach deep into the ultrafaint regime to $M_V \sim -6$ (similar to current limits for Andromeda satellites). These candidates' luminosities and sizes are similar to known Local Group dwarf galaxies Tucana B, Canes Venatici I, Hercules, and Bo\"otes I. Most of these candidates are likely to be real, based on tests of our techniques on blank fields. Intriguingly, all of these candidates are spatially clustered around NGC 3077, which is itself an M81 group satellite in an advanced state of tidal disruption. This is somewhat surprising, as M81 itself and its largest satellite M82 are both substantially more massive than NGC 3077 and by virtue of their greater masses, would have been expected to host as many or more ultrafaint candidates. These results lend considerable support to the idea that satellites of satellites are an important contribution to the growth of satellite populations around Milky Way-mass galaxies.Comment: The Astrophysical Journal Letters; in press. 11 pages, 4 figures, 1 tabl

Ultrafaint Dwarf Galaxy Candidates in the M81 Group: Signatures of Group Accretion

The faint and ultrafaint dwarf galaxies in the Local Group form the observational bedrock upon which our understanding of small-scale cosmology rests. In order to understand whether this insight generalizes, it is imperative to use resolved-star techniques to discover similarly faint satellites in nearby galaxy groups. We describe our search for ultrafaint galaxies in the M81 group using deep ground-based resolved-star data sets from Subaru’s Hyper Suprime-Cam. We present one new ultrafaint dwarf galaxy in the M81 group and identify five additional extremely low surface brightness candidate ultrafaint dwarfs that reach deep into the ultrafaint regime to M V ∼ − 6 (similar to current limits for Andromeda satellites). These candidates’ luminosities and sizes are similar to known Local Group dwarf galaxies Tucana B, Canes Venatici I, Hercules, and Boötes I. Most of these candidates are likely to be real, based on tests of our techniques on blank fields. Intriguingly, all of these candidates are spatially clustered around NGC 3077, which is itself an M81 group satellite in an advanced state of tidal disruption. This is somewhat surprising, as M81 itself and its largest satellite M82 are both substantially more massive than NGC 3077 and, by virtue of their greater masses, would have been expected to host as many or more ultrafaint candidates. These results lend considerable support to the idea that satellites of satellites are an important contribution to the growth of satellite populations around Milky Way-mass galaxies

SCUBA sub-millimeter observations of gamma-ray bursters: II. GRB 991208, 991216, 000301C, 000630, 000911, 000926

We discuss our ongoing program of Target of Opportunity sub-millimeter observations of gamma-ray bursts (GRBs) using the Sub-millimetre Common-User Bolometer Array (SCUBA) on the James Clerk Maxwell Telescope (JCMT). Sub-millimeter observations of the early afterglows are of interest because this is where the emission peaks in some bursts in the days to weeks following the burst. Of increasing interest is to look for underlying quiescent sub-millimeter sources that may be dusty star-forming host galaxies. In this paper, we present observations of GRB 991208, 991216, 000301C, 000630, 000911, and 000926. For all these bursts, any sub-millimeter emission is consistent with coming from the afterglow. This means that we did not conclusively detect quiescent sub-millimeter counterparts to any of the bursts that were studied from 1997 through 2000. The inferred star formation rates (M > 5 Msun) are typically < 300 Msun/yr. If GRBs are due to the explosions of high-mass stars, this may indicate that the relatively small population of extremely luminous dusty galaxies does not dominate the total star formation in the universe at early epochs. Instead, the GRBs may be predominantly tracing slightly lower luminosity galaxies. The optical faintness of some host galaxies is unlikely to be explained as due to dust absorption in the host.Comment: 9 pages. 0 figures. Astronomy and Astrophysics, in pres