Development of acoustically lined ejector technology for multitube jet noise suppressor nozzles by model and engine tests over a wide range of jet pressure ratios and temperatures

An experimental program comprising model nozzle and full-scale engine tests was undertaken to acquire parametric data for acoustically lined ejectors applied to primary jet noise suppression. Ejector lining design technology and acoustical scaling of lined ejector configurations were the major objectives. Ground static tests were run with a J-75 turbojet engine fitted with a 37-tube, area ratio 3.3 suppressor nozzle and two lengths of ejector shroud (L/D = 1 and 2). Seven ejector lining configurations were tested over the engine pressure ratio range of 1.40 to 2.40 with corresponding jet velocities between 305 and 610 M/sec. One-fourth scale model nozzles were tested over a pressure ratio range of 1.40 to 4.0 with jet total temperatures between ambient and 1088 K. Scaling of multielement nozzle ejector configurations was also studied using a single element of the nozzle array with identical ejector lengths and lining materials. Acoustic far field and near field data together with nozzle thrust performance and jet aerodynamic flow profiles are presented

Kritik an Population Attributable Fraction bei genauerem Hinsehen nicht gerechtfertigt

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An online supported self-management toolkit for relatives of people with psychosis or bipolar experiences: the IMPART multiple case study

Background Digital health interventions have the potential to improve the delivery of psychoeducation to people with mental health problems and their relatives. Despite substantial investment in the development of digital health interventions, successful implementation into routine clinical practice is rare. Objectives Use the implementation of the Relatives’ Education And Coping Toolkit (REACT) for psychosis/bipolar disorder to identify critical factors affecting uptake and use, and develop an implementation plan to support the delivery of REACT. Design This was an implementation study using a mixed-methods, theory-driven, multiple case study approach. A study-specific implementation theory for REACT based on normalisation process theory was developed and tested, and iterations of an implementation plan to address the key factors affecting implementation were developed. Setting Early-intervention teams in six NHS mental health trusts in England (three in the north and three in the south). Participants In total, 281 staff accounts and 159 relatives’ accounts were created, 129 staff and 23 relatives took part in qualitative interviews about their experiences, and 132 relatives provided demographic data, 56 provided baseline data, 21 provided data at 12 weeks’ follow-up and 20 provided data at 24 weeks’ follow-up. Interventions REACT is an online supported self-management toolkit, offering 12 evidence-based psychoeducation modules and support via a forum, and a confidential direct messaging service for relatives of people with psychosis or bipolar disorder. The implementation intervention was developed with staff and iteratively adapted to address identified barriers. Adaptations included modifications to the toolkit and how it was delivered by teams. Main outcome measures The main outcome was factors affecting implementation of REACT, assessed primarily through in-depth interviews with staff and relatives. We also assessed quantitative measures of delivery (staff accounts and relatives’ invitations), use of REACT (relatives’ logins and time spent on the website) and the impact of REACT [relatives’ distress (General Health Questionnaire-28), and carer well-being and support (Carer Well-being and Support Scale questionnaire)]. Results Staff and relatives were generally positive about the content of REACT, seeing it as a valuable resource that could help services improve support and meet clinical targets, but only within a comprehensive service that included face-to-face support, and with some additional content. Barriers to implementation included high staff caseloads and difficulties with prioritising supporting relatives; technical difficulties of using REACT; poor interoperability with trust information technology systems and care pathways; lack of access to mobile technology and information technology training; restricted forum populations leading to low levels of use; staff fears of managing risk, online trolling, or replacement by technology; and uncertainty around REACT’s long-term availability. There was no evidence that REACT would reduce staff time supporting relatives (which was already very low), and might increase it by facilitating communication. In all, 281 staff accounts were created, but only 57 staff sent relatives invitations. In total, 355 relatives’ invitations were sent to 310 unique relatives, leading to the creation of 159 relatives’ accounts. The mean number of logins for relatives was 3.78 (standard deviation 4.43), but with wide variation from 0 to 31 (median 2, interquartile range 1–8). The mean total time spent on the website was 40.6 minutes (standard deviation 54.54 minutes), with a range of 0–298 minutes (median 20.1 minutes, interquartile range 4.9–57.5 minutes). There was a pattern of declining mean scores for distress, social dysfunction, depression, anxiety and insomnia, and increases in relatives’ well-being and eHealth literacy, but no changes were statistically significant. Conclusions Digital health interventions, such as REACT, should be iteratively developed, evaluated, adapted and implemented, with staff and service user input, as part of a long-term strategy to develop integrated technology-enabled services. Implementation strategies must instil a sense of ownership for staff and ensure that they have adequate training, risk protocols and resources to deliver the technology. Cost-effectiveness and impact on workload and inequalities in accessing health care need further testing, along with the generalisability of our findings to other digital health interventions. Limitations REACT was offered by the same team running the IMPlementation of A Relatives’ Toolkit (IMPART) study, and was perceived by staff and relatives as a time-limited research study rather than ongoing clinical service, which affected engagement. Access to observational data was limited. Trial registration Current Controlled Trials ISRCTN16267685. Funding This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 8, No. 37. See the NIHR Journals Library website for further project information

Construction of Modern Robust Nodal Discontinuous Galerkin Spectral Element Methods for the Compressible Navier-Stokes Equations

Discontinuous Galerkin (DG) methods have a long history in computational physics and engineering to approximate solutions of partial differential equations due to their high-order accuracy and geometric flexibility. However, DG is not perfect and there remain some issues. Concerning robustness, DG has undergone an extensive transformation over the past seven years into its modern form that provides statements on solution boundedness for linear and nonlinear problems. This chapter takes a constructive approach to introduce a modern incarnation of the DG spectral element method for the compressible Navier-Stokes equations in a three-dimensional curvilinear context. The groundwork of the numerical scheme comes from classic principles of spectral methods including polynomial approximations and Gauss-type quadratures. We identify aliasing as one underlying cause of the robustness issues for classical DG spectral methods. Removing said aliasing errors requires a particular differentiation matrix and careful discretization of the advective flux terms in the governing equations.Comment: 85 pages, 2 figures, book chapte

Phase I Hydroxylated Metabolites of the K2 Synthetic Cannabinoid JWH-018 Retain In Vitro and In Vivo Cannabinoid 1 Receptor Affinity and Activity

K2 products are synthetic cannabinoid-laced, marijuana-like drugs of abuse, use of which is often associated with clinical symptoms atypical of marijuana use, including hypertension, agitation, hallucinations, psychosis, seizures and panic attacks. JWH-018, a prevalent K2 synthetic cannabinoid, is structurally distinct from Δ(9)-THC, the main psychoactive ingredient in marijuana. Since even subtle structural differences can lead to differential metabolism, formation of novel, biologically active metabolites may be responsible for the distinct effects associated with K2 use. The present study proposes that K2's high adverse effect occurrence is due, at least in part, to distinct JWH-018 metabolite activity at the cannabinoid 1 receptor (CB1R).JWH-018, five potential monohydroxylated metabolites (M1-M5), and one carboxy metabolite (M6) were examined in mouse brain homogenates containing CB1Rs, first for CB1R affinity using a competition binding assay employing the cannabinoid receptor radioligand [(3)H]CP-55,940, and then for CB1R intrinsic efficacy using an [(35)S]GTPγS binding assay. JWH-018 and M1-M5 bound CB1Rs with high affinity, exhibiting K(i) values that were lower than or equivalent to Δ(9)-THC. These molecules also stimulated G-proteins with equal or greater efficacy relative to Δ(9)-THC, a CB1R partial agonist. Most importantly, JWH-018, M2, M3, and M5 produced full CB1R agonist levels of activation. CB1R-mediated activation was demonstrated by blockade with O-2050, a CB1R-selective neutral antagonist. Similar to Δ(9)-THC, JWH-018 and M1 produced a marked depression of locomotor activity and core body temperature in mice that were both blocked by the CB1R-preferring antagonist/inverse agonist AM251.Unlike metabolites of most drugs, the studied JWH-018 monohydroxylated compounds, but not the carboxy metabolite, retain in vitro and in vivo activity at CB1Rs. These observations, combined with higher CB1R affinity and activity relative to Δ(9)-THC, may contribute to the greater prevalence of adverse effects observed with JWH-018-containing products relative to cannabis

A New Role for Translation Initiation Factor 2 in Maintaining Genome Integrity

Escherichia coli translation initiation factor 2 (IF2) performs the unexpected function of promoting transition from recombination to replication during bacteriophage Mu transposition in vitro, leading to initiation by replication restart proteins. This function has suggested a role of IF2 in engaging cellular restart mechanisms and regulating the maintenance of genome integrity. To examine the potential effect of IF2 on restart mechanisms, we characterized its influence on cellular recovery following DNA damage by methyl methanesulfonate (MMS) and UV damage. Mutations that prevent expression of full-length IF2-1 or truncated IF2-2 and IF2-3 isoforms affected cellular growth or recovery following DNA damage differently, influencing different restart mechanisms. A deletion mutant (del1) expressing only IF2-2/3 was severely sensitive to growth in the presence of DNA-damaging agent MMS. Proficient as wild type in repairing DNA lesions and promoting replication restart upon removal of MMS, this mutant was nevertheless unable to sustain cell growth in the presence of MMS; however, growth in MMS could be partly restored by disruption of sulA, which encodes a cell division inhibitor induced during replication fork arrest. Moreover, such characteristics of del1 MMS sensitivity were shared by restart mutant priA300, which encodes a helicase-deficient restart protein. Epistasis analysis indicated that del1 in combination with priA300 had no further effects on cellular recovery from MMS and UV treatment; however, the del2/3 mutation, which allows expression of only IF2-1, synergistically increased UV sensitivity in combination with priA300. The results indicate that full-length IF2, in a function distinct from truncated forms, influences the engagement or activity of restart functions dependent on PriA helicase, allowing cellular growth when a DNA–damaging agent is present

The Cryo-EM Structure of a Complete 30S Translation Initiation Complex from Escherichia coli

Formation of the 30S initiation complex (30S IC) is an important checkpoint in regulation of gene expression. The selection of mRNA, correct start codon, and the initiator fMet-tRNAfMet requires the presence of three initiation factors (IF1, IF2, IF3) of which IF3 and IF1 control the fidelity of the process, while IF2 recruits fMet-tRNAfMet. Here we present a cryo-EM reconstruction of the complete 30S IC, containing mRNA, fMet-tRNAfMet, IF1, IF2, and IF3. In the 30S IC, IF2 contacts IF1, the 30S subunit shoulder, and the CCA end of fMet-tRNAfMet, which occupies a novel P/I position (P/I1). The N-terminal domain of IF3 contacts the tRNA, whereas the C-terminal domain is bound to the platform of the 30S subunit. Binding of initiation factors and fMet-tRNAfMet induces a rotation of the head relative to the body of the 30S subunit, which is likely to prevail through 50S subunit joining until GTP hydrolysis and dissociation of IF2 take place. The structure provides insights into the mechanism of mRNA selection during translation initiation