Dynamics of the Lyman alpha and C IV emitting gas in 3C 273

In this paper we study the variability properties of the Lyman alpha and C IV emission lines in 3C273 using archival IUE observations. Our data show for the first time the existence of variability on time scales of several years. We study the spatial distribution and the velocity field of the emitting gas by performing detailed analyses on the line variability using correlations, 1D and 2D response functions, and principal component analysis. In both lines we find evidence for two components, one which has the dynamic properties of gas in Keplerian motion around a black hole with a mass of the order of 10^9 Mo, and one which is characterized by high, blue-shifted velocities at large lag. There is no indication of the presence of optically thick emission medium neither in the Lya, nor in the Civ response functions. The component characterized by blue-shifted velocities, which is comparatively much stronger in Civ than in Lya, is more or less compatible with being the result of gas falling towards the central black hole with free-fall acceleration. We propose however that the line emission at high, blue-shifted velocities is better explained in terms of entrainment of gas clouds by the jet. This gas is therefore probably collisionally excited as a result of heating due to the intense infrared radiation from the jet, which would explain the strength of this component in Civ relative to Lya. This phenomenon might be a signature of disk-jet interaction.Comment: 16 pages, 10 figures. Accepted for publication in ApJ. Uses aaste

Evidence for the horizontal acquisition of murine AKR virogenes by recent horizontal infection of the germ line

Several recent reports (8, 10, 11, 13) have established the biological and molecular genetic similarity between the endogenous AKV virus of strain AKR, and an N-ecotropic endogenous virus found in the genome of feral Japanese mice, Mus musculus molossinus. The similarities are so striking as to suggest a common origin of these viruses, which are present in some, but not all, inbred mouse strains. The virogenes of AKR mice may have been acquired by either: (a) common descent of AKR (and other AKV(+) strains) from a common ancestor of AKR and molossinus animals, or (b) horizontal germ line infection of the AKR strains by molossinus virus at 1;he strain’s inception followed by fixation through inbreeding. The sexual descent model carries with it a prediction of relative consanguinity of the AKR strain and molossinus, whereas the horizontal infection model does not. We have examined the polymorphic allozyme (allelic isozyme) genotype of 51 nonvirus-related loci in 17 strains of mice including AKR, C58, BALB/c, Swiss, and molossinus. By comparing the composite allozyme genotype of different inbred and outbred mouse strains, the “genetic distance” statistic was derived. Genetic distance measures the degree of allelic substitution between populations and increases proportionately with the amount of time the populations have been reproductively isolated. The genetic distance computed between molossinus and AKR is large, nearly 5-10 times the distance between known related populations and strains (e.g., C57L vs. C57BL/6). Molossinus had a similarly large distance from AKV negative strains (Swiss, C57L) as it did from AKV- positive strains. Cellular DNA sequences that flank the integrated AKV provirus were analyzed by restriction enzyme digestion of liver DNA from molossinus, AKR, and additional inbred strains that express ecotropic murine leukemia virus. The integration flanks of three AKR provirus sequences, Akv-1, Akv-2, and a third uncharacterized sequence, were not evident in molossinus cell DNA, which contained at least six different proviral integration fragments. These data effectively exclude the interpretation of consanguinity of AKR and molossinus and support the notion of acquisition of the endogenous virus in AKR by horizontal infection of the molossinus virus

Safer Prescribing:A Trial of Education, Informatics, and Financial Incentives

BACKGROUND High-risk prescribing and preventable drug-related complications are common in primary care. We evaluated whether the rates of high-risk prescribing by primary care clinicians and the related clinical outcomes would be reduced by a complex intervention. METHODS In this cluster-randomized, stepped-wedge trial conducted in Tayside, Scotland, we randomly assigned participating primary care practices to various start dates for a 48-week intervention comprising professional education, informatics to facilitate review, and financial incentives for practices to review patients’ charts to assess appropriateness. The primary outcome was patient-level exposure to any of nine measures of high-risk prescribing of nonsteroidal antiinflammatory drugs (NSAIDs) or selected antiplatelet agents (e.g., NSAID prescription in a patient with chronic kidney disease or coprescription of an NSAID and an oral anticoagulant without gastroprotection). Prespecified secondary outcomes included the incidence of related hospital admissions. Analyses were performed according to the intention-to-treat principle, with the use of mixed-effect models to account for clustering in the data. RESULTS A total of 34 practices underwent randomization, 33 of which completed the study. Data were analyzed for 33,334 patients at risk at one or more points in the preintervention period and for 33,060 at risk at one or more points in the intervention period. Targeted high-risk prescribing was significantly reduced, from a rate of 3.7% (1102 of 29,537 patients at risk) immediately before the intervention to 2.2% (674 of 30,187) at the end of the intervention (adjusted odds ratio, 0.63; 95% confidence interval [CI], 0.57 to 0.68; P<0.001). The rate of hospital admissions for gastrointestinal ulcer or bleeding was significantly reduced from the preintervention period to the intervention period (from 55.7 to 37.0 admissions per 10,000 person-years; rate ratio, 0.66; 95% CI, 0.51 to 0.86; P = 0.002), as was the rate of admissions for heart failure (from 707.7 to 513.5 admissions per 10,000 person-years; rate ratio, 0.73; 95% CI, 0.56 to 0.95; P = 0.02), but admissions for acute kidney injury were not (101.9 and 86.0 admissions per 10,000 person-years, respectively; rate ratio, 0.84; 95% CI, 0.68 to 1.09; P = 0.19). CONCLUSIONS A complex intervention combining professional education, informatics, and financial incentives reduced the rate of high-risk prescribing of antiplatelet medications and NSAIDs and may have improved clinical outcomes

Pancreatic transdifferentiation and glucose-regulated production of human insulin in the H4IIE rat liver cell line

© 2016 by the authors. Due to the limitations of current treatment regimes, gene therapy is a promising strategy being explored to correct blood glucose concentrations in diabetic patients. In the current study, we used a retroviral vector to deliver either the human insulin gene alone, the rat NeuroD1 gene alone, or the human insulin gene and rat NeuroD1 genes together, to the rat liver cell line, H4IIE, to determine if storage of insulin and pancreatic transdifferentiation occurred. Stable clones were selected and expanded into cell lines: H4IIEins (insulin gene alone), H4IIE/ND (NeuroD1 gene alone), and H4IIEins/ND (insulin and NeuroD1 genes). The H4IIEins cells did not store insulin; however, H4IIE/ND and H4IIEins/ND cells stored 65.5 ± 5.6 and 1475.4 ± 171.8 pmol/insulin/ 5 × 106 cells, respectively. Additionally, several β cell transcription factors and pancreatic hormones were expressed in both H4IIE/ND and H4IIEins/ND cells. Electron microscopy revealed insulin storage vesicles in the H4IIE/ND and H4IIEins/ND cell lines. Regulated secretion of insulin to glucose (0–20 mmol/L) was seen in the H4IIEins/ND cell line. The H4IIEins/ND cells were transplanted into diabetic immunoincompetent mice, resulting in normalization of blood glucose. This data shows that the expression of NeuroD1 and insulin in liver cells may be a useful strategy for inducing islet neogenesis and reversing diabetes

What keeps FLAME lit? Comparing two modes of implementation of a physical education-based intervention to improve motor competence among Irish adolescents

Background: Adequate levels of motor competence (MC) have been associated with multiple health outcomes. Despite the preponderance of effective MC interventions, globally, levels of MC in children and adolescents are low. There is a gap in understanding what leads to effective implementation of MC interventions into routine practice, to benefit the wider population. Purpose: This study aims to compare implementation outcomes of two versions of Project FLAME: one group of teachers implementing Project FLAME as per the original efficacy trial (‘Original FLAME’), a second group of teachers implementing Project FLAME incorporating three additional implementation strategies (‘Modified FLAME’). Methods: A mixed method, two-group pre-and-post design, lasting six weeks during the period of September to November 2021. Three implementation evaluation outcomes were assessed: (i) PE teacher’s self-efficacy in delivering Project FLAME; (ii) Fidelity and adaptation to the project protocol; and (iii) Teachers’ and students’ responsiveness to the project. Data were collected at student and teacher levels using online survey and interviews. Nine PE teachers and their classes from eight schools consented to participate. Descriptives were reported for quantitative online survey data, and qualitative data were analysed thematically. Results: The final analytical sample included data from 9 teachers and 127 students pre- and post-study. Irrespective of implementation group, teachers with low levels of self-efficacy at the baseline improved after the six-week intervention. Teachers’ fidelity to the use of pedagogical external cues and error identification were high in both groups, with more adaptations made in the Modified FLAME group. Students’ satisfaction towards the intervention was high in both groups, with the use of pedagogical external cues reported as highly preferable. Conclusion: Findings provide evidence on the ‘non-negotiable’ features of Project FLAME that have the potential to be implemented for a longer-term in Physical Education settings (e.g. external teaching cues). The documented implementation of Project FLAME provide knowledge on what adaptations may be needed to translate an effective MC intervention into real-world practice. The study reaffirms that documenting the implementation (especially fidelity and adaptation) of MC interventions is beneficial.</p

Planning for a cohort study to investigate the impact and management of influenza in pregnancy in a future pandemic

Background: Evidence from the 2009 A/H1N1 influenza pandemic demonstrated that pregnant women are particularly vulnerable to infection and at an increased risk of death. Active data collection through the UK Obstetric Surveillance System (UKOSS) about women admitted to hospital during the 2009 A/H1N1 pandemic was used to inform ongoing clinical guidance regarding the use of antiviral treatment for pregnant women and demonstrated that, in addition to an increased risk of maternal morbidity, influenza infection in pregnancy is associated with poor perinatal outcomes, including an increased risk of stillbirth and preterm birth. This evidence influenced the decision to offer routine influenza immunisation to pregnant women. Even in a non-epidemic period, pregnant women continue to die from influenza. Objective: To establish, and then to put into hibernation, the study mechanisms needed to mount a rapid investigation of the impact of pandemic influenza in pregnancy in the event of a newly emerging pandemic strain. Design: A new UKOSS cohort study was designed, based on the 2009–10 study, and following consultation with the Pandemic Flu Planning Group at the Royal College of Obstetricians and Gynaecologists and the UKOSS Steering Committee, to identify potential previously unanswered questions. Setting: UK maternity units. Participants: All pregnant women admitted to hospital with influenza in a future pandemic. Main outcome measures: Management of pregnant women with influenza infection, intervention rates, treatment and pregnancy outcome for both the mother and fetus. Results: The study was designed and approved by the UKOSS Steering Committee and then placed into hibernation for activation in the event of an influenza pandemic. Conclusions: Pregnant women, as a result of their changed immunological status, appear to be particularly susceptible to infection, including from influenza. The existence of the UKOSS enabled us to rapidly mount a study of pregnant women who were hospitalised with 2009 A/H1N1 influenza. Minor modifications to incorporate previously unanswered questions and our previous study enabled us to design, and then put into hibernation, a new study ready to investigate the impact and management of influenza in pregnancy, which is poised for activation in the event of a newly emerging pandemic strain. This will enable real-time data to be available on which to base rapid changes in clinical management as the as-yet-unforeseen pandemic unfolds. In the event of an influenza pandemic the study will be available to be immediately activated following expedited regulatory approvals. Trial registration: Current Controlled Trials ISRCTN44137563. Funding: The National Institute for Health Research Health Services and Delivery Research programme

Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial

This analysis from the phase II BRIGHT AML 1003 trial reports the long-term efficacy and safety of glasdegib + low-dose cytarabine (LDAC) in patients with acute myeloid leukemia ineligible for intensive chemotherapy. The multicenter, open-label study randomized (2:1) patients to receive glasdegib + LDAC (de novo, n = 38; secondary acute myeloid leukemia, n = 40) or LDAC alone (de novo, n = 18; secondary acute myeloid leukemia, n = 20). At the time of analysis, 90% of patients had died, with the longest follow-up since randomization 36 months. The combination of glasdegib and LDAC conferred superior overall survival (OS) versus LDAC alone; hazard ratio (HR) 0.495; (95% confidence interval [CI] 0.325–0.752); p = 0.0004; median OS was 8.3 versus 4.3 months. Improvement in OS was consistent across cytogenetic risk groups. In a post-hoc subgroup analysis, a survival trend with glasdegib + LDAC was observed in patients with de novo acute myeloid leukemia (HR 0.720; 95% CI 0.395–1.312; p = 0.14; median OS 6.6 vs 4.3 months) and secondary acute myeloid leukemia (HR 0.287; 95% CI 0.151–0.548; p < 0.0001; median OS 9.1 vs 4.1 months). The incidence of adverse events in the glasdegib + LDAC arm decreased after 90 days’ therapy: 83.7% versus 98.7% during the first 90 days. Glasdegib + LDAC versus LDAC alone continued to demonstrate superior OS in patients with acute myeloid leukemia; the clinical benefit with glasdegib + LDAC was particularly prominent in patients with secondary acute myeloid leukemia. ClinicalTrials.gov identifier: NCT01546038.Open Access funding enabled and organized by Projekt DEAL. This study was funded by Pfizer.Peer reviewe

d dimensional SO(d)-Higgs Models with Instanton and Sphaleron: d=2,3

The Abelian Higgs model and the Georgi-Glashow model in 2 and 3 Euclidean dimensions respectively, support both finite size instantons and sphalerons. The instantons are the familiar Nielsen-Oleson vortices and the 't Hooft-Polyakov monopole solutions respectively. We have constructed the sphaleron solutions and calculated the Chern-Simons charges N_cs for sphalerons of both models and have constructed two types of noncontractible loops between topologically distinct vacuua. In the 3 dimensional model, the sphaleron and the vacuua have zero magnetic and electric flux while the configurations on the loops have non vanishing magnetic flux.Comment: 24 pages, 3 figures, LaTe

Garden varieties: how attractive are recommended garden plants to butterflies?

One way the public can engage in insect conservation is through wildlife gardening, including the growing of insect-friendly flowers as sources of nectar. However, plant varieties differ in the types of insects they attract. To determine which garden plants attracted which butterflies, we counted butterflies nectaring on 11 varieties of summer-flowering garden plants in a rural garden in East Sussex, UK. These plants were all from a list of 100 varieties considered attractive to British butterflies, and included the five varieties specifically listed by the UK charity Butterfly Conservation as best for summer nectar. A total of 2659 flower visits from 14 butterfly and one moth species were observed. We performed a principal components analysis which showed contrasting patterns between the species attracted to Origanum vulgare and Buddleia davidii. The “butterfly bush” Buddleia attracted many nymphalines, such as the peacock, Inachis io, but very few satyrines such as the gatekeeper, Pyronia tithonus, which mostly visited Origanum. Eupatorium cannibinum had the highest Simpson’s Diversity score of 0.75, while Buddleia and Origanum were lower, scoring 0.66 and 0.50 respectively. No one plant was good at attracting all observed butterfly species, as each attracted only a subset of the butterfly community. We conclude that to create a butterfly-friendly garden, a variety of plant species are required as nectar sources for butterflies. Furthermore, garden plant recommendations can probably benefit from being more precise as to the species of butterfly they attract

Decadal changes of the Western Arabian sea ecosystem

Historical data from oceanographic expeditions and remotely sensed data on outgoing longwave radiation, temperature, wind speed and ocean color in the western Arabian Sea (1950–2010) were used to investigate decadal trends in the physical and biochemical properties of the upper 300 m. 72 % of the 29,043 vertical profiles retrieved originated from USA and UK expeditions. Increasing outgoing longwave radiation, surface air temperatures and sea surface temperature were identified on decadal timescales. These were well correlated with decreasing wind speeds associated with a reduced Siberian High atmospheric anomaly. Shoaling of the oxycline and nitracline was observed as well as acidification of the upper 300 m. These physical and chemical changes were accompanied by declining chlorophyll-a concentrations, vertical macrofaunal habitat compression, declining sardine landings and an increase of fish kill incidents along the Omani coast