Characterisation of a Desmosterol Reductase Involved in Phytosterol Dealkylation in the Silkworm, Bombyx mori

Most species of invertebrate animals cannot synthesise sterols de novo and many that feed on plants dealkylate phytosterols (mostly C29 and C28) yielding cholesterol (C27). The final step of this dealkylation pathway involves desmosterol reductase (DHCR24)-catalysed reduction of desmosterol to cholesterol. We now report the molecular characterisation in the silkworm, Bombyx mori, of such a desmosterol reductase involved in production of cholesterol from phytosterol, rather than in de novo synthesis of cholesterol. Phylogenomic analysis of putative desmosterol reductases revealed the occurrence of various clades that allowed for the identification of a strong reductase candidate gene in Bombyx mori (BGIBMGA 005735). Following PCR-based cloning of the cDNA (1.6 kb) and its heterologous expression in Saccharomyces cerevisae, the recombinant protein catalysed reduction of desmosterol to cholesterol in an NADH- and FAD- dependent reaction

Space Telescope and Optical Reverberation Mapping Project. IX. Velocity–Delay Maps for Broad Emission Lines in NGC 5548

In this contribution, we achieve the primary goal of the active galactic nucleus (AGN) STORM campaign by recovering velocity–delay maps for the prominent broad emission lines (Lyα, C iv, He ii, and Hβ) in the spectrum of NGC 5548. These are the most detailed velocity–delay maps ever obtained for an AGN, providing unprecedented information on the geometry, ionization structure, and kinematics of the broad-line region. Virial envelopes enclosing the emission-line responses show that the reverberating gas is bound to the black hole. A stratified ionization structure is evident. The He ii response inside 5–10 lt-day has a broad single-peaked velocity profile. The Lyα, C iv, and Hβ responses extend from inside 2 to outside 20 lt-day, with double peaks at ±2500 km s−1 in the 10–20 lt-day delay range. An incomplete ellipse in the velocity–delay plane is evident in Hβ. We interpret the maps in terms of a Keplerian disk with a well-defined outer rim at R = 20 lt-day. The far-side response is weaker than that from the near side. The line-center delay $\tau =(R/c)(1-\sin i)\approx 5$ days gives the inclination i ≈ 45°. The inferred black hole mass is MBH ≈ 7 × 107 M⊙. In addition to reverberations, the fit residuals confirm that emission-line fluxes are depressed during the "BLR Holiday" identified in previous work. Moreover, a helical "Barber-Pole" pattern, with stripes moving from red to blue across the C iv and Lyα line profiles, suggests azimuthal structure rotating with a 2 yr period that may represent precession or orbital motion of inner-disk structures casting shadows on the emission-line region farther out

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

The role of community pharmacy-based vaccination in the USA: current practice and future directions

Albert T Bach, Jeffery A Goad School of Pharmacy, Chapman University, Irvine, California, USA Abstract: Community pharmacy-based provision of immunizations in the USA has become commonplace in the last few decades, with success in increasing rates of immunizations. Community pharmacy-based vaccination services are provided by pharmacists educated in the practice of immunization delivery and provide a convenient and accessible option for receiving immunizations. The pharmacist's role in immunization practice has been described as serving in the roles of educator, facilitator, and immunizer. With a majority of pharmacist-provided vaccinations occurring in the community pharmacy setting, there are many examples of community pharmacists serving in these immunization roles with successful outcomes. Different community pharmacies employ a number of different models and workflow practices that usually consist of a year-round in-house service staffed by their own immunizing pharmacist. Challenges that currently exist in this setting are variability in scopes of immunization practice for pharmacists across states, inconsistent reimbursement mechanisms, and barriers in technology. Many of these challenges can be alleviated by continual education; working with legislators, state boards of pharmacy, stakeholders, and payers to standardize laws; and reimbursement design. Other challenges that may need to be addressed are improvements in communication and continuity of care between community pharmacists and the patient centered medical home. Keywords: immunization, pharmacy practice, pharmacists, continuity of care&nbsp

The role of community pharmacy-based vaccination in the USA: current practice and future directions

Albert T Bach, Jeffery A Goad School of Pharmacy, Chapman University, Irvine, California, USA Abstract: Community pharmacy-based provision of immunizations in the USA has become commonplace in the last few decades, with success in increasing rates of immunizations. Community pharmacy-based vaccination services are provided by pharmacists educated in the practice of immunization delivery and provide a convenient and accessible option for receiving immunizations. The pharmacist's role in immunization practice has been described as serving in the roles of educator, facilitator, and immunizer. With a majority of pharmacist-provided vaccinations occurring in the community pharmacy setting, there are many examples of community pharmacists serving in these immunization roles with successful outcomes. Different community pharmacies employ a number of different models and workflow practices that usually consist of a year-round in-house service staffed by their own immunizing pharmacist. Challenges that currently exist in this setting are variability in scopes of immunization practice for pharmacists across states, inconsistent reimbursement mechanisms, and barriers in technology. Many of these challenges can be alleviated by continual education; working with legislators, state boards of pharmacy, stakeholders, and payers to standardize laws; and reimbursement design. Other challenges that may need to be addressed are improvements in communication and continuity of care between community pharmacists and the patient centered medical home. Keywords: immunization, pharmacy practice, pharmacists, continuity of care&nbsp

On the multiwavelength variability of Mrk 110: two components acting at different time-scales

We present the first intensive continuum reverberation mapping study of the high accretion-rate Seyfert galaxy Mrk 110. The source was monitored almost daily for more than 200 d with the Swift X-ray and ultraviolet (UV)/optical telescopes, supported by ground-based observations from Las Cumbres Observatory, the Liverpool Telescope, and the Zowada Observatory, thus extending the wavelength coverage to 9100 Å. Mrk 110 was found to be significantly variable at all wavebands. Analysis of the intraband lags reveals two different behaviours, depending on the time-scale. On time-scales shorter than 10 d the lags, relative to the shortest UV waveband (∼1928 Å), increase with increasing wavelength up to a maximum of ∼2 d lag for the longest waveband (∼9100 Å), consistent with the expectation from disc reverberation. On longer time-scales, however, the g-band lags the Swift BAT hard X-rays by ∼10 d, with the z-band lagging the g-band by a similar amount, which cannot be explained in terms of simple reprocessing from the accretion disc. We interpret this result as an interplay between the emission from the accretion disc and diffuse continuum radiation from the broad-line region