High quality, patient centred andcoordinated care for Alstrom syndrome: amodel of care for an ultra-rare disease

Background: Patients with rare and ultra-rare diseases make heavy demands on the resources of both health and social services, but these resources are often used inefficiently due to delays in diagnosis, poor and fragmented care. We analysed the national service for an ultra-rare disease, Alstrom syndrome, and compared the outcome and cost of the service to the standard care. Methods: Between the 9th and 26th of March 2014 we undertook a cross-sectional study of the UK Alstrom syndrome patients and their carers. We developed a semi-structured questionnaire to assess our rare patient need, quality of care and costs incurred to patients and their careers. In the UK all Alstrom syndrome patients are seen in two centres, based in Birmingham, and we systematically evaluated the national service and compared the quality and cost of care with patients’ previous standard of care. Results: One quarter of genetically confirmed Alstrom syndrome UK patients were enrolled in this study. Patients that have access to a highly specialised clinical service reported that their care is well organised, personalised, holistic, and that they have a say in their care. All patients reported high level of satisfaction in their care. Patient treatment compliance and clinic attendance was better in multidisciplinary clinic than the usual standard of NHS care. Following a variable costing approach based on personnel and consumables’ cost, our valuation of the clinics was just under £700/patient/annum compared to the standard care of £960/patient/annum. Real savings, however, came in terms of patients’ quality of life. Furthermore there was found to have been a significant reduction in frequency of clinic visits and ordering of investigations since the establishment of the national service. Conclusions: Our study has shown that organised, multidisciplinary “one stop” clinics are patient centred and individually tailored to the patient need with a better outcome and comparable cost compared with the current standard of care for rare disease. Our proposed care model can be adapted to several other rare and ultra-rare diseases

Spatially resolved spectroscopy of Cassiopeia A with MECS on board BeppoSAX

We have performed the first detailed spatially resolved spectroscopy of Cas A in the 1.6-10 keV energy range, using data taken with the MECS spectrometer on board the BeppoSAX Observatory. We performed a spatial deconvolution of the data and eventually generated a set of spectra, covering a region of about 3 arcmin radius around the centre of Cas A. The results obtained by fitting these spectra using a non-equilibrium ionisation plasma model and a power law, are: (i) a single thermal component is sufficient to fit all the spectra; (ii) kT is rather uniformly distributed with a minimum in the east and a maximum in the west, and no evidence is found for high kT expected from the interaction of the main shock with the ISM; (iii) from the distribution of the values of the ionisation parameter n_et we infer the presence of two distinct components: the first (a) in the range 1-10 cm^(-3), the second (b) with values ten times higher; if we associate component a to the CSM and component b to the ejecta, the mass ratio M(a)/M(b)<= 1/10 indicates a progenitor star that lost only a small fraction of the envelope during its pre-SN life. In this hypothesis the distribution of component b across the remnant suggests that the explosion was not spherically symmetric; (iv) the distribution of abundances indicates that we are detecting a CSM component with almost solar composition, and an ejecta component enriched in heavier elements. Abundances found for alpha-elements are consistent with the current view that Cas A was produced by the explosion of a massive star.Comment: 16 pages, 9 PostScript figures, 4 tables, Accepted for publication on Astronomy & Astrophysics (submitted July 12, 2000; accepted December 20, 2000

Transient dust in warm debris disks - Detection of Fe-rich olivine grains

(Abridged) Debris disks trace remnant reservoirs of leftover planetesimals in planetary systems. A handful of "warm" debris disks have been discovered in the last years, where emission in excess starts in the mid-infrared. An interesting subset within these warm debris disks are those where emission features are detected in mid-IR spectra, which points towards the presence of warm micron-sized dust grains. Given the ages of the host stars, the presence of these grains is puzzling, and questions their origin and survival in time. This study focuses on determining the mineralogy of the dust around 7 debris disks with evidence for warm dust, based on Spitzer/IRS spectroscopic data, in order to provide new insights into the origin of the dust grains. We present a new radiative transfer code dedicated to SED modeling of optically thin disks. We make use of this code on the SEDs of seven warm debris disks, in combination with recent laboratory experiments on dust optical properties. We find that most, if not all, debris disks in our sample are experiencing a transient phase, suggesting a production of small dust grains on relatively short timescales. From a mineralogical point of view, we find that enstatite grains have small abundances compared to crystalline olivine grains. The main result of our study is that we find evidences for Fe-rich crystalline olivine grains (Fe / [Mg + Fe] ~ 0.2) for several debris disks. This finding contrasts with studies of gas-rich protoplanetary disks. The presence of Fe-rich olivine grains, and the overall differences between the mineralogy of dust in Class II disks compared to debris disks suggest that the transient crystalline dust is of a new generation. We discuss possible crystallization routes to explain our results, and comment on the mechanisms that may be responsible for the production of small dust grains

Alloherpesviruses of Fish

The family Alloherpesviridae includes herpesviruses of fish and amphibians. This group of viruses are phylogenetically distant from the better characterized herpesviruses found in birds and mammals. However, many biological and structural properties are conserved in the order Herpesvirales. The known alloherpesviruses typically exhibit host specificity which is a biological feature shared by nearly all herpesviruses. Of the alloherpesviruses of fish at least 11 cause significant economic losses to aquaculture. These include: Ictalurid herpesvirus 1 and 2 (IcHV1, 2) impacting catfish aquaculture; Cyprinid herpesvirus 1, 2 and 3 (CyHV1-3) impacting carp and goldfish aquaculture; Anguillid herpesvirus 1 (AngHV1) impacting eel aquaculture; Acipenserid herpesvirus 1 and 2 (AciHV1, 2) impacting sturgeon aquaculture; and Salmonid herpesvirus 2, 3 and 4 (SalHV2-4) impacting salmon and trout aquaculture. The most notable impact has been koi herpesvirus disease caused by Cyprinid herpesvirus 3. This virus has caused devastating losses worldwide in all strains of common carp and is an OIE notifiable pathogen

An attenuated herpesvirus vectored vaccine candidate induces T-cell responses against highly conserved porcine reproductive and respiratory syndrome virus M and NSP5 proteins that are unable to control infection

Porcine reproductive and respiratory syndrome virus (PRRSV) remains a leading cause of economic loss in pig farming worldwide. Existing commercial vaccines, all based on modified live or inactivated PRRSV, fail to provide effective immunity against the highly diverse circulating strains of both PRRSV-1 and PRRSV-2. Therefore, there is an urgent need to develop more effective and broadly active PRRSV vaccines. In the absence of neutralizing antibodies, T cells are thought to play a central role in controlling PRRSV infection. Herpesvirus-based vectors are novel vaccine platforms capable of inducing high levels of T cells against encoded heterologous antigens. Therefore, the aim of this study was to assess the immunogenicity and efficacy of an attenuated herpesvirus-based vector (bovine herpesvirus-4; BoHV-4) expressing a fusion protein comprising two well-characterized PRRSV-1 T-cell antigens (M and NSP5). Prime-boost immunization of pigs with BoHV-4 expressing the M and NSP5 fusion protein (vector designated BoHV-4-M-NSP5) induced strong IFN-γ responses, as assessed by ELISpot assays of peripheral blood mononuclear cells (PBMC) stimulated with a pool of peptides representing PRRSV-1 M and NSP5. The responses were closely mirrored by spontaneous IFN-γ release from unstimulated cells, albeit at lower levels. A lower frequency of M and NSP5 specific IFN-γ responding cells was induced following a single dose of BoHV-4-M-NSP5 vector. Restimulation using M and NSP5 peptides from PRRSV-2 demonstrated a high level of cross-reactivity. Vaccination with BoHV-4-M-NSP5 did not affect viral loads in either the blood or lungs following challenge with the two heterologous PRRSV-1 strains. However, the BoHV-4-M-NSP5 prime-boost vaccination showed a marked trend toward reduced lung pathology following PRRSV-1 challenge. The limited effect of T cells on PRRSV-1 viral load was further examined by analyzing local and circulating T-cell responses using intracellular cytokine staining and proliferation assays. The results from this study suggest that vaccine-primed T-cell responses may have helped in the control of PRRSV-1 associated tissue damage, but had a minimal, if any, effect on controlling PRRSV-1 viral loads. Together, these results indicate that future efforts to develop effective PRRSV vaccines should focus on achieving a balanced T-cell and antibody response

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort