Going home after infant cardiac surgery: a UK qualitative study

National Institute for Health Research Health Services and Delivery Research programme (Project No: 10/2002/29)

Comparative Therapeutic Effects of Velaglucerase Alfa and Imiglucerase in a Gaucher Disease Mouse Model

Gaucher disease type 1 is caused by the defective activity of the lysosomal enzyme, acid β-glucosidase (GCase). Regular infusions of purified recombinant GCase are the standard of care for reversing hematologic, hepatic, splenic, and bony manifestations. Here, similar in vitro enzymatic properties, and in vivo pharmacokinetics and pharmacodynamics (PK/PD) and therapeutic efficacy of GCase were found with two human GCases, recombinant GCase (CHO cell, imiglucerase, Imig) and gene-activated GCase (human fibrosarcoma cells, velaglucerase alfa, Vela), in a Gaucher mouse, D409V/null. About 80+% of either enzyme localized to the liver interstitial cells and <5% was recovered in spleens and lungs after bolus i.v. injections. Glucosylceramide (GC) levels and storage cell numbers were reduced in a dose (5, 15 or 60 U/kg/wk) dependent manner in livers (60–95%) and in spleens (∼10–30%). Compared to Vela, Imig (60 U/kg/wk) had lesser effects at reducing hepatic GC (p = 0.0199) by 4 wks; this difference disappeared by 8 wks when nearly WT levels were achieved by Imig. Anti-GCase IgG was detected in GCase treated mice at 60 U/kg/wk, and IgE mediated acute hypersensitivity and death occurred after several injections of 60 U/kg/wk (21% with Vela and 34% with Imig). The responses of GC levels and storage cell numbers in Vela- and Imig-treated Gaucher mice at various doses provide a backdrop for clinical applications and decisions

Genome Sequences of Streptomyces Phages Amela and Verse

This article describes Amela and Verse, two Streptomyces phages isolated by enrichment on Streptomyces venezuelae (ATCC 10712) from two different soil samples

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

The Effects of Curriculum Structure on the Achievement of Grade 3 and Grade 5 Mobile Students as Measured by the Maryland School Assessment

School systems are under continual pressure to increase student achievement on high-stakes tests and make Adequate Yearly Progress based on the No Child Left Behind mandate. One population which struggles to achieve on such tests is the mobile student population. Recent studies have shown that these students do not typically score as high on standardized tests as the stable student population. While past studies have focused on the ethnicity and socio-economic status of mobile students, very little research has been conducted to examine the effects of curriculum structure on the achievement of these students. This study examines the effects of synchronous and non-synchronous curriculum structure on mathematics and reading achievement in mobile and non-mobile students as measured by the Maryland School Assessment (MSA). Using third and fifth grade data from 2003-2004 MSA Mathematics and Reading, a two-way analysis of variance was conducted to analyze data from two Maryland school districts with differing curriculum structures. Non-mobile, with-in-school district mobile, and out-of-school district mobile student data were evaluated. Combined third and fifth grade data were examined, as well as data from each grade level, independently. Significant differences were found in the mean scores of non-mobile and mobile students, with the non-mobile students recurrently having the highest mean score in sub-test areas. No differences were found between mean scores based on curriculum structure, nor the interaction of curriculum structure and mobility status. The author provides recommendations for practice and further research

Words and Wordsmiths Front matter

On December 31, 1987, Leslie Rogers retired as McCaughey Professor of Early English Literature and Language at the University of Sydney, a Chair which he had held since July 4, 1966. The co-sponsorship of this volume by The University of Sydney Arts Association, of which he has been Secretary and President, and The Sydney Association for Studies in Society and Culture marks an appreciation of his long and active membership of the Faculty of Arts. Early in his career at Sydney, where, in 1958, he took up a Senior Lectureship in the Department of English, Leslie became Sub-Dean (1960--62) to Professor John Dunston and, subsequently, Pro-Dean to Professor Ralph Farrell in 1967. From 1968-71 he was Dean of the Faculty, during a busy period of re-structuring and expansion of the faculty system. He has served twice as a Fellow of Senate, first (1968-69) in his capacity as Dean, and later (1974-75) as one of three professorial Fellows· elected by the academic staff

Disappearance of Vela or Imig in spleen of 20-wk (left) or 5-wk (right) 9 V/null mice.

<p>GCase activities in spleen were determined from 20 min to 42 h post-injection and represented as fold of WT (WT = 1) as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010750#pone-0010750-g002" target="_blank">Figure 2</a>. The disappearances of Vela or Imig activities were plotted as fold WT (activity panels) or from the 20-min (20-wk) or 40-min (5-wk) peak values (% peak activity panels). The GCase activities in spleen from saline-injected mice were 8.1% (SE = ±0.017) of WT (<b>X</b>, solid line at the bottom of top panels). Disappearances of Vela or Imig proteins (CRIM panels) up to 42 h post-injection were analyzed by immunoblots as per <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010750#pone-0010750-g002" target="_blank">Figure 2</a>.</p

Recovery of Vela or Imig activity in serum and organs of 9 V/null mice^A.

A<p>The recovery of injected Vela or Imig was calculated as the percentage (% ± SE) of total serum or whole organ activity at the peak of enzyme activity following a bolus of 60 U/kg injection.</p>B<p>The peak activity in serum was 2 min post injection.</p>C<p>The peak activity in liver and lung was 20 min post injection.</p>D<p>The peak activity in spleen was at 40 min in 5-wk mice and 20 min in 20-wk mice post injection.</p