VLBA Imaging of the OH Maser in IIIZw35

We present a parsec-scale image of the OH maser in the nucleus of the active galaxy IIIZw35, made using the Very Long Baseline Array at a wavelength of 18 cm. We detected two distinct components, with a projected separation of 50 pc (for D=110 Mpc) and a separation in Doppler velocity of 70 km/s, which contain 50% of the total maser flux. Velocity gradients within these components could indicate rotation of clouds with binding mass densities of ~7000 solar masses per cubic parsec, or total masses of more than 500,000 solar masses. Emission in the 1665-MHz OH line is roughly coincident in position with that in the 1667-MHz line, although the lines peak at different Doppler velocities. We detected no 18 cm continuum emission; our upper limit implies a peak apparent optical depth greater than 3.4, assuming the maser is an unsaturated amplifier of continuum radiation.Comment: 10 pages, 3 figure

SLN124, a GalNAc conjugated 19-mer siRNA targeting tmprss6, reduces plasma iron and increases hepcidin levels of healthy volunteers

SLN124, an N-acetylgalactosamine conjugated 19-mer short interfering RNA, is being developed to treat iron-loading anemias (including beta-thalassemia and myelodysplastic syndromes) and myeloproliferative neoplasms (polycythemia vera). Through hepatic targeting and silencing of the TMPRSS6 gene, SLN124 increases endogenous hepcidin synthesis. This is the first clinical report of an siRNA targeting a component of iron homeostasis. This first-in-human, phase 1 study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of SLN124 (1.0, 3.0, and 4.5 mg/kg) in healthy volunteers. Twenty-four participants were randomized in three sequential cohorts of eight subjects, each to receive a single dose of either SLN124 or placebo (6:2 randomization), administered subcutaneously. There were no serious or severe adverse events, or discontinuations due to adverse events, and most treatment-emergent adverse events were mild, including transient mild injection site reactions, resolving without intervention. SLN124 was rapidly absorbed, with a median tmax of 4–5 h across all treatment groups, and largely eliminated from plasma by 48 h. Plasma concentrations increased in a greater than dose proportional fashion between treatment groups. In all SLN124 groups, a dose-related effect was observed across iron metabolism markers, and across erythroid markers, SLN124 resulted in increased plasma hepcidin levels, peaking around Day 29, and consequent dose-related sustained reductions in plasma iron and transferrin saturation with decreased reticulocyte production, MCHC, and MCV. Results suggest duration of action lasting up to 56 days after a single SLN124 dose, on hepcidin and hematological parameters of iron metabolism (serum iron and TSAT)

Sclerostin Downregulation Globally by Naturally Occurring Genetic Variants, or Locally in Atherosclerotic Plaques, Does Not Associate With Cardiovascular Events in Humans

Inhibition of sclerostin increases bone formation and decreases bone resorption, leading to increased bone mass, bone mineral density, and bone strength and reduced fracture risk. In a clinical study of the sclerostin antibody romosozumab versus alendronate in postmenopausal women (ARCH), an imbalance in adjudicated serious cardiovascular (CV) adverse events driven by an increase in myocardial infarction (MI) and stroke was observed. To explore whether there was a potential mechanistic plausibility that sclerostin expression, or its inhibition, in atherosclerotic (AS) plaques may have contributed to this imbalance, sclerostin was immunostained in human plaques to determine whether it was detected in regions relevant to plaque stability in 94 carotid and 50 femoral AS plaques surgically collected from older female patients (mean age 69.6 ± 10.4 years). Sclerostin staining was absent in most plaques (67%), and when detected, it was of reduced intensity compared with normal aorta and was located in deeper regions of the plaque/wall but was not observed in areas considered relevant to plaque stability (fibrous cap and endothelium). Additionally, genetic variants associated with lifelong reduced sclerostin expression were explored for associations with phenotypes including those related to bone physiology and CV risk factors/events in a population-based phenomewide association study (PheWAS). Natural genetic modulation of sclerostin by variants with a significant positive effect on bone physiology showed no association with lifetime risk of MI or stroke. These data do not support a causal association between the presence of sclerostin, or its inhibition, in the vasculature and increased risk of serious cardiovascular events

Property Prices and Real Estate Financing in a Turbulent World

On 15th November 2012 in Copenhagen, SUERF and Nykredit in association with Danmarks Nationalbank organised a conference on “Property prices and real estate financing in a turbulent world.” The papers included in this SUERF Study are based on contributions to the conference

Are food and drink retailers within NHS venues adhering to NICE Quality standard 94 guidance on childhood obesity?:A cross-sectional study of two large secondary care NHS hospitals in England

ObjectiveTo assess whether the food and drink retail outlets in two major National Health Service (NHS) district general hospitals in England adhere to quality statements 1–3 of the UK National Institute for Health and Care Excellence (NICE) quality standard 94.DesignCross-sectional, descriptive study to assess the food and drink options available in vending machines, restaurants, cafes and shops in two secondary care hospitals.Main outcome measuresAdherence to quality statement 1 whereby the food and drink items available in the vending machines were classified as either healthy or less healthy using the Nutrient Profiling Model (NPM). Compliance with quality statements 2 and 3 was assessed through the measurement of how clearly the shops, cafes and restaurants displayed nutrition information on menus, and the availability and prominent display of healthy food and drink options in retail outlets, respectively.ResultsAdherence to quality statement 1 was poor. Of the 18 vending machines assessed, only 7 (39%) served both a healthy food and a healthy drink option. Neither hospital was compliant with quality statement 2 wherein nutritional information was not available on menus of food providers in either hospital. There was inconsistent compliance with quality standard 3 whereby healthy food and drink options were prominently displayed in the two main hospital restaurants, but all shops and cafes prioritised the display of unhealthy items.ConclusionsNeither hospital was consistently compliant with quality statements 1–3 of the NICE quality standard 94. Improving the availability of healthy foods and drinks while reducing the display and accessibility to less healthy options in NHS venues may improve family awareness of healthy alternatives. Making it easier for parents to direct their children to healthier choices is an ostensibly central component of our healthcare system.</jats:sec

Design and On-Orbit Operation of the Soft X-Ray Spectrometer Adiabatic Demagnetization Refrigerator on the Hitomi Observatory

The Soft X-ray Spectrometer (SXS) instrument that flew on the Astro-H observatory was designed to perform imaging and spectroscopy of x-rays in the energy range of 0.2 to 13 keV with a resolution requirement of 7 eV or better. This was accomplished using a 6x6 array of x-ray microcalorimeters cooled to an operating temperature of 50 mK by an adiabatic demagnetization refrigerator (ADR). The ADR consisted of three stages in order to operate using either a 1.2 K superfluid helium bath or a 4.5 K Joule-Thomson (JT) cryocooler as its heat sink. The design was based on the following operating strategy. After launch, while liquid helium was present (cryogen mode), two of the ADRs stages would be used to single-shot cool the detectors, using the helium as a heat sink. When the helium was eventually depleted (cryogen-free mode), all three ADR stages would be used to continuously cool the helium tank to about 1.5 K, and to single-shot cool the detectors (to 50 mK), using the JT cryocooler as a heat sink. The Astro-H observatory, renamed Hitomi after its successful launch in February 2016, carried approximately 36 liters of helium into orbit. Based on measurements during ground testing, the average heat load on the helium was projected to be 0.66 mW, giving a lifetime of more than 4 years. On day 5, the helium had cooled to <1.4 K and ADR operation began, successfully cooling the detector array to 50 mK. The ADRs hold time steadily increased to 48 hours as the helium cooled to a temperature of 1.12 K. As the commissioning phase progressed, the ADR was recycled (requiring approximately 45 minutes) periodically, either in preparation for science observations or whenever the 50 mK stage approached the end of its hold time. In total, 18 cycles were completed by the time an attitude control anomaly led to an unrecoverable failure of the satellite on day 38. This paper presents the design, operation and on-orbit performance of the ADR in cryogen mode as the foreshortened mission did not provide an opportunity to test cryogen-free mode

Design and On-Orbit Operation of the Adiabatic Demagnetization Refrigerator on the Hitomi Soft X-Ray Spectrometer Instrument

The Soft X-ray Spectrometer instrument on the Astro-H observatory contains a 6x6 array of x-ray microcalorimeters that is cooled to 50 mK by an adiabatic demagnetization refrigerator (ADR). The ADR consists of three stages in order to provide stable detector cooling using either a 1.2 K superfluid helium bath or a 4.5 K Joule-Thomson (JT) cryocooler as its heat sink. When liquid helium is present, two of the ADR's stages are used to single-shot cool the detectors while rejecting heat to the helium. After the helium is depleted, all three stages are used to continuously cool the helium tank (to about 1.5 K) and single-shot cool the detectors (to 50 mK), using the JT cryocooler as its heat sink. The Astro-H observatory, renamed Hitomi after its successful launch in February 2016, carried approximately 36 liters of helium into orbit. On day 5, the helium had cooled sufficiently (<1.4 K) to allow operation of the ADR. This paper describes the design, operation and on-orbit performance of the ADR, and the use of the ADR's heat rejection as a tool for mass gauging the helium tank

A systematic review of the effectiveness and cost-effectiveness of peer education and peer support in prisons.

BACKGROUND: Prisoners experience significantly worse health than the general population. This review examines the effectiveness and cost-effectiveness of peer interventions in prison settings. METHODS: A mixed methods systematic review of effectiveness and cost-effectiveness studies, including qualitative and quantitative synthesis was conducted. In addition to grey literature identified and searches of websites, nineteen electronic databases were searched from 1985 to 2012. Study selection criteria were: Population: Prisoners resident in adult prisons and children resident in Young Offender Institutions (YOIs). INTERVENTION: Peer-based interventions Comparators: Review questions 3 and 4 compared peer and professionally led approaches. OUTCOMES: Prisoner health or determinants of health; organisational/ process outcomes; views of prison populations. STUDY DESIGNS: Quantitative, qualitative and mixed method evaluations. RESULTS: Fifty-seven studies were included in the effectiveness review and one study in the cost-effectiveness review; most were of poor methodological quality. Evidence suggested that peer education interventions are effective at reducing risky behaviours, and that peer support services are acceptable within the prison environment and have a positive effect on recipients, practically or emotionally. Consistent evidence from many, predominantly qualitative, studies, suggested that being a peer deliverer was associated with positive effects. There was little evidence on cost-effectiveness of peer-based interventions. CONCLUSIONS: There is consistent evidence from a large number of studies that being a peer worker is associated with positive health; peer support services are also an acceptable source of help within the prison environment and can have a positive effect on recipients. Research into cost-effectiveness is sparse. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ref: CRD42012002349

CRTAP Is Required for Prolyl 3- Hydroxylation and Mutations Cause Recessive Osteogenesis Imperfecta

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