Novel flaviviruses from mosquitoes: Mosquito-specific evolutionary lineages within the phylogenetic group of mosquito-borne flaviviruses

Copyright © 2014 The Authors. Published by Elsevier Inc. 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. The attached file is the published version of the article

The ILIUM forward modelling algorithm for multivariate parameter estimation and its application to derive stellar parameters from Gaia spectrophotometry

I introduce an algorithm for estimating parameters from multidimensional data based on forward modelling. In contrast to many machine learning approaches it avoids fitting an inverse model and the problems associated with this. The algorithm makes explicit use of the sensitivities of the data to the parameters, with the goal of better treating parameters which only have a weak impact on the data. The forward modelling approach provides uncertainty (full covariance) estimates in the predicted parameters as well as a goodness-of-fit for observations. I demonstrate the algorithm, ILIUM, with the estimation of stellar astrophysical parameters (APs) from simulations of the low resolution spectrophotometry to be obtained by Gaia. The AP accuracy is competitive with that obtained by a support vector machine. For example, for zero extinction stars covering a wide range of metallicity, surface gravity and temperature, ILIUM can estimate Teff to an accuracy of 0.3% at G=15 and to 4% for (lower signal-to-noise ratio) spectra at G=20. [Fe/H] and logg can be estimated to accuracies of 0.1-0.4dex for stars with G<=18.5. If extinction varies a priori over a wide range (Av=0-10mag), then Teff and Av can be estimated quite accurately (3-4% and 0.1-0.2mag respectively at G=15), but there is a strong and ubiquitous degeneracy in these parameters which limits our ability to estimate either accurately at faint magnitudes. Using the forward model we can map these degeneracies (in advance), and thus provide a complete probability distribution over solutions. (Abridged)Comment: MNRAS, in press. This revision corrects a few minor errors and typos. A better formatted version for A4 paper is available at http://www.mpia.de/home/calj/ilium.pd

Identification and characterization of a novel non-structural protein of bluetongue virus

Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell

A SEARCH for AN OPTICAL COUNTERPART to the GRAVITATIONAL-WAVE EVENT GW151226

We present a search for an electromagnetic counterpart of the gravitational-wave source GW151226. Using the Pan-STARRS1 telescope we mapped out 290 square degrees in the optical $i_{P1}$ filter, starting 11.5 hr after the LIGO information release and lasting for an additional 28 days. The first observations started 49.5 hr after the time of the GW151226 detection. We typically reached sensitivity limits of $i_{P1}$ = 20.3–20.8 and covered 26.5% of the LIGO probability skymap. We supplemented this with ATLAS survey data, reaching 31% of the probability region to shallower depths of $m \simeq$ 19. We found 49 extragalactic transients (that are not obviously active galactic nuclei), including a faint transient in a galaxy at 7 Mpc (a luminous blue variable outburst) plus a rapidly decaying M-dwarf flare. Spectral classification of 20 other transient events showed them all to be supernovae. We found an unusual transient, PS15dpn, with an explosion date temporally coincident with GW151226, that evolved into a type Ibn supernova. The redshift of the transient is secure at $z$ = 0.1747 ± 0.0001 and we find it unlikely to be linked, since the luminosity distance has a negligible probability of being consistent with that of GW151226. In the 290 square degrees surveyed we therefore do not find a likely counterpart. However we show that our survey strategy would be sensitive to NS–NS mergers producing kilonovae at $D_L \lesssim$ 100 Mpc, which is promising for future LIGO/Virgo searches.NASA (Grant IDs: NNX08AR22G, NNX12AR65G, NNX14AM74G, NNX12AR55G), EU/FP7-ERC (Grant IDs: 291222, 307260, 320360, 615929), a Weizmann-UK Making Connections Grant, STFC (Ernest Rutherford Fellowship), Alexander von Humboldt Foundation (Sofia Kovalevskaja Award), National Science Foundation (Grant ID: AST-1238877)This is the final version of the article. It first appeared from Institute of Physics Publishing via http://dx.doi.org/10.3847/2041-8205/827/2/L4

The implementation evaluation of primary care groups of practice: a focus on organizational identity

<p>Abstract</p> <p>Background</p> <p>Since 2002 the Health Ministry of Québec (Canada) has been implementing a primary care organizational innovation called 'family medicine groups'. This is occurring in a political context in which the reorganization of primary care is considered necessary to improve health care system performance. More specifically, the purpose of this reform has been to overcome systemic deficiencies in terms of accessibility and continuity of care. This paper examines the first years of implementation of the family medicine group program, with a focus on the emergence of the organizational identity of one of the pilot groups located in the urban area of Montreal.</p> <p>Methods</p> <p>An in-depth longitudinal case study was conducted over two and a half years. Face to face individual interviews with key informants from the family medicine group under study were conducted over the research period considered. Data was gathered throuhg observations and documentary analysis. The data was analyzed using temporal bracketing and Fairclough's three-dimensional critical discourse analytical techniques.</p> <p>Results</p> <p>Three different phases were identified over the period under study. During the first phase, which corresponded to the official start-up of the family medicine group program, new resources and staff were only available at the end of the period, and no changes occurred in medical practices. Power struggles between physicians and nurses characterized the second phase, resulting in a very difficult integration of advanced nurse practitioners into the group. Indeed, the last phase was portrayed by initial collaborative practices associated with a sensegiving process prompted by a new family medicine group director.</p> <p>Conclusions</p> <p>The creation of a primary care team is a very challenging process that goes beyond the normative policy definitions of who is on the team or what the team has to do. To fulfil expectations of quality improvement through team-based care, health care professionals who are required to work together need shared time/space contexts to communicate; to overcome interprofessional and interpersonal conflicts; and to make sense of and define who they collectively are and what they do as a clinical team.</p

Interpreting the role of de novo protein-coding mutations in neuropsychiatric disease

Pedigree, linkage and association studies are consistent with heritable variation for complex disease due to the segregation of genetic factors in families and in the population. In contrast, de novo mutations make only minor contributions to heritability estimates for complex traits. Nonetheless, some de novo variants are known to be important in disease etiology. The identification of risk-conferring de novo variants will contribute to the discovery of etiologically relevant genes and pathways and may help in genetic counseling. There is considerable interest in the role of such mutations in complex neuropsychiatric disease, largely driven by new genotyping and sequencing technologies. An important role for large de novo copy number variations has been established. Recently, whole-exome sequencing has been used to extend the investigation of de novo variation to point mutations in protein-coding regions. Here, we consider several challenges for the interpretation of such mutations in the context of their role in neuropsychiatric disease

Analgesic management of an eight-year-old Springer Spaniel after amputation of a thoracic limb

Analgesic agents were administered perioperatively to an eight-year-old Springer Spaniel undergoing amputation of its right thoracic limb. The amputation was carried out due to a painful, infiltrative and poorly differentiated sarcoma involving the nerves of the brachial plexus. A combination of pre-emptive and multimodal perioperative analgesic strategies was used; including intravenous (IV) infusions of fentanyl, morphine, lidocaine and ketamine

Randomised control trial of the effectiveness of an integrated psychosocial health promotion intervention aimed at improving health and reducing substance use in established psychosis (IMPaCT)

© 2017 The Author(s). Background: People with psychosis have a reduced life expectancy of 10-20years, largely due to cardiovascular disease. This trial aimed to determine the effectiveness of a modular health promotion intervention (IMPaCT Therapy) in improving health and reducing cardiovascular risk in psychosis. Methods: A multicentre, two arm, parallel cluster RCT was conducted across five UK mental health NHS trusts. Community care coordinators (CC) were randomly assigned to training and supervision in delivering IMPaCT Therapy or treatment as usual (TAU) to current patients with psychosis (cluster). The primary outcome was the physical and mental health subscales of the Short form-36 (SF-36) questionnaire. Results: Of 104 care coordinators recruited, 52 (with 213 patients) were randomised to deliver IMPaCT therapy and 52 (with 193 patients) randomised to TAU. Of 406 patients, 318 (78%) and 301 (74%) attended 12- and 15-month follow-up respectively. IMPaCT therapy showed no significant effect on the physical or mental health component SF-36 scores versus TAU at 12 or 15months. No effect was observed for cardiovascular risk indicators, except for HDL cholesterol, which improved more with IMPACT therapy than TAU (Treatment effect (95% CI); 0.085 (0.007 to 0.16); p= 0.034). The 22% of patients who received > 180min of IMPACT Therapy in addition to usual care achieved a greater reduction in waist circumference than did controls, which was clinically significant. Conclusion: Training and supervising community care coordinators to use IMPaCT therapy in patients with psychosis is insufficient to significantly improve physical or mental health quality of life. The search for effective, pragmatic interventions deliverable in health care services continues. Trial registration: The trial was retrospectively registered with ISRCTN registry on 23/4/2010 at ISRCTN58667926 ; recruitment started on 01/03/2010 with first randomization on 09.08.2010 ISRCTN58667926