Development of life prediction capabilities for liquid propellant rocket engines. Post-fire diagnostic system for the SSME system architecture study

This system architecture task (1) analyzed the current process used to make an assessment of engine and component health after each test or flight firing of an SSME, (2) developed an approach and a specific set of objectives and requirements for automated diagnostics during post fire health assessment, and (3) listed and described the software applications required to implement this system. The diagnostic system described is a distributed system with a database management system to store diagnostic information and test data, a CAE package for visual data analysis and preparation of plots of hot-fire data, a set of procedural applications for routine anomaly detection, and an expert system for the advanced anomaly detection and evaluation

Hydrocarbon-fuel/combustion-chamber-liner materials compatibility

Results of material compatibility experiments using hydrocarbon fuels in contact with copper-based combustion chamber liner materials are presented. Mil-Spec RP-1, n- dodecane, propane, and methane fuels were tested in contact with OFHC, NASA-Z, and ZrCu coppers. Two distinct test methods were employed. Static tests, in which copper coupons were exposed to fuel for long durations at constant temperature and pressure, provided compatibility data in a precisely controlled environment. Dynamic tests, using the Aerojet Carbothermal Test Facility, provided fuel and copper compatibility data under realistic booster engine service conditions. Tests were conducted using very pure grades of each fuel and fuels to which a contaminant, e.g., ethylene or methyl mercaptan, was added to define the role played by fuel impurities. Conclusions are reached as to degradation mechanisms and effects, methods for the elimination of these mechanisms, selection of copper alloy combustion chamber liners, and hydrocarbon fuel purchase specifications

Pitx2 is an upstream activator of extraocular myogenesis and survival

AbstractThe transcription factors required to initiate myogenesis in branchial arch- and somite-derived muscles are known, but the comparable upstream factors required during extraocular muscle development have not been identified. We show Pax7 is dispensable for extraocular muscle formation, whereas Pitx2 is cell-autonomously required to prevent apoptosis of the extraocular muscle primordia. The survival requirement for Pitx2 is stage-dependent and ends following stable activation of genes for the muscle regulatory factors (e.g. Myf5, MyoD), which is reduced in the absence of Pitx2. Further, PITX2 binds and activates transcription of the Myf5 and MyoD promoters, indicating these genes are direct targets. Collectively, these data demonstrate that PITX2 is required at several steps in the development of extraocular muscles, acting first as an anti-apoptotic factor in pre-myogenic mesoderm, and subsequently to activate the myogenic program in these cells. Thus, Pitx2 is the first demonstrated upstream activator of myogenesis in the extraocular muscles

Grasshopper DCMD : an undergraduate electrophysiology lab for investigating single-unit responses to behaviorally-relevant stimuli

Author Posting. © Faculty for Undergraduate Neuroscience, 2017. This article is posted here by permission of Faculty for Undergraduate Neuroscience for personal use, not for redistribution. The definitive version was published in Journal of Undergraduate Neuroscience Education 15 (2017): A162-A173.Avoiding capture from a fast-approaching predator is an important survival skill shared by many animals. Investigating the neural circuits that give rise to this escape behavior can provide a tractable demonstration of systems-level neuroscience research for undergraduate laboratories. In this paper, we describe three related hands-on exercises using the grasshopper and affordable technology to bring neurophysiology, neuroethology, and neural computation to life and enhance student understanding and interest. We simplified a looming stimuli procedure using the Backyard Brains SpikerBox bioamplifier, an open-source and low-cost electrophysiology rig, to extracellularly record activity of the descending contralateral movement detector (DCMD) neuron from the grasshopper’s neck. The DCMD activity underlies the grasshopper's motor responses to looming monocular visual cues and can easily be recorded and analyzed on an open-source iOS oscilloscope app, Spike Recorder. Visual stimuli are presented to the grasshopper by this same mobile application allowing for synchronized recording of stimuli and neural activity. An in-app spike-sorting algorithm is described that allows a quick way for students to record, sort, and analyze their data at the bench. We also describe a way for students to export these data to other analysis tools. With the protocol described, students will be able to prepare the grasshopper, find and record from the DCMD neuron, and visualize the DCMD responses to quantitatively investigate the escape system by adjusting the speed and size of simulated approaching objects. We describe the results from 22 grasshoppers, where 50 of the 57 recording sessions (87.7%) had a reliable DCMD response. Finally, we field-tested our experiment in an undergraduate neuroscience laboratory and found that a majority of students (67%) could perform this exercise in one two-hour lab setting, and had an increase in interest for studying the neural systems that drive behavior.Funding for this project was supported by the National Institute of Mental Health Small Business Innovation Research grant #2R44MH093334: “Backyard Brains: Bringing Neurophysiology into Secondary Schools.

Increasing access to CBT for psychosis patients: a feasibility, randomised controlled trial evaluating brief, targeted CBT for distressing voices delivered by assistant psychologists (GiVE2)

Background: The National Institute for Health and Care Excellence (NICE) recommends that Cognitive Behaviour Therapy for psychosis (CBTp) is offered to all patients with a psychosis diagnosis. However, only a minority of psychosis patients in England and Wales are offered CBTp. This is attributable, in part, to the resource-intensive nature of CBTp. One response to this problem has been the development of CBTp in brief formats that are targeted at a single symptom and the mechanisms that maintain distress. We have developed a brief form of CBTp for distressing voices and reported preliminary evidence for its effectiveness when delivered by highly trained therapists (clinical psychologists). This study will investigate the delivery of this intervention by a cost-effective workforce of assistant psychologists following a brief training and evaluate the acceptability and feasibility of conducting a future, definitive, randomised controlled trial (RCT). Methods: This is a feasibility study for a pragmatic, three-arm, parallel-group, superiority 1:1:1 RCT comparing a Guided self-help CBT intervention for voices and treatment as usual (GiVE) to Supportive Counselling and treatment as usual (SC) to treatment as usual alone (TAU), recruiting across two sites, with blinded post-treatment and follow-up assessments. A process evaluation will quantitatively and qualitatively explore stakeholder experience. Discussion: Expected outcomes will include an assessment of the feasibility of conducting a definitive RCT, and data to inform the calculation of its sample size. If evidence from a subsequent, fully powered RCT suggests that GiVE is clinically and cost-effective when delivered by briefly trained assistant psychologists, CBTp offered in these less resource-intensive forms has the potential to generate benefits for individual patients (reduced distress, enhanced recovery and enhanced quality of life), service-level patient benefit (increased access to evidence-based psychological therapies) and economic benefits to the NHS (in terms of the reduced use of mental health inpatient services). Trial registration: Current Controlled Trials, ISRCTN registration number: 16166070. Registered on 5 February 2019

Charged particle tracking via edge-classifying interaction networks

Recent work has demonstrated that geometric deep learning methods such as graph neural networks (GNNs) are well suited to address a variety of reconstruction problems in high energy particle physics. In particular, particle tracking data is naturally represented as a graph by identifying silicon tracker hits as nodes and particle trajectories as edges; given a set of hypothesized edges, edge-classifying GNNs identify those corresponding to real particle trajectories. In this work, we adapt the physics-motivated interaction network (IN) GNN toward the problem of particle tracking in pileup conditions similar to those expected at the high-luminosity Large Hadron Collider. Assuming idealized hit filtering at various particle momenta thresholds, we demonstrate the IN's excellent edge-classification accuracy and tracking efficiency through a suite of measurements at each stage of GNN-based tracking: graph construction, edge classification, and track building. The proposed IN architecture is substantially smaller than previously studied GNN tracking architectures; this is particularly promising as a reduction in size is critical for enabling GNN-based tracking in constrained computing environments. Furthermore, the IN may be represented as either a set of explicit matrix operations or a message passing GNN. Efforts are underway to accelerate each representation via heterogeneous computing resources towards both high-level and low-latency triggering applications.Comment: This is a post-peer-review, pre-copyedit version of this article. The final authenticated version is available online at: https://doi.org/10.1007/s41781-021-00073-

Reporting of lost to follow-up and treatment discontinuation in device and pharmacotherapy trials in chronic heart failure: a systematic review

Background—Premature treatment discontinuation and loss to follow-up (LTFU) with unknown outcomes leave uncertainty about the true efficacy and safety of a treatment and a lack of confidence in the results of any trial. We reviewed the extent of (and trends over time in) reporting LTFU and treatment discontinuation in large studies in chronic heart failure published since 1990. Methods and Results—Online databases were systematically reviewed to identify randomized controlled clinical trials (RCTs) in chronic heart failure with >400 participants and utilizing all-cause mortality as a component of the primary or secondary end point. Assessments were made of documentation of treatment discontinuation, LTFU, inclusion of and completeness of a Consolidated Standards Of Reporting Trials (CONSORT) diagram, and whether LTFU was differentiated from withdrawal of consent. Sixty-eight trials were identified, with >154 000 participants. Reasons for treatment discontinuation in pharmacotherapy trials were infrequently reported (35%), particularly in a CONSORT diagram (20%). Eighty-three percent of trials reported LTFU, although only 34% of these differentiated LTFU for vital status from withdrawal of consent. Use of a CONSORT diagram increased over time, although reporting of LTFU in the CONSORT diagram remained low overall at 35%. Conclusions—Participant flow through RCTs in chronic heart failure has not been uniformly reported, and the use of a complete CONSORT diagram has been low, although it seems to be improving. All study participants should be accounted for within a CONSORT diagram in any RCT to enable the practicing cardiologist to interpret how the results should influence his/her clinical practice

Calcium Handling Defects and Cardiac Arrhythmia Syndromes

K

A proposed new generation of evidence-based microsimulation models to inform global control of cervical cancer

Health decision models are the only available tools designed to consider the lifetime natural history of human papillomavirus (HPV) infection and pathogenesis of cervical cancer, and the estimated long-term impact of preventive interventions. Yet health decision modeling results are often considered a lesser form of scientific evidence due to the inherent needs to rely on imperfect data and make numerous assumptions and extrapolations regarding complex processes. We propose a new health decision modeling framework that de-emphasizes cytologic-colposcopic-histologic diagnoses due to their subjectivity and lack of reproducibility, relying instead on HPV type and duration of infection as the major determinants of subsequent transition probabilities. We posit that the new model health states (normal, carcinogenic HPV infection, precancer, cancer) and corollary transitions are universal, but that the probabilities of transitioning between states may vary by population. Evidence for this variability in host response to HPV infections can be inferred from HPV prevalence patterns in different regions across the lifespan, and might be linked to different average population levels of immunologic control of HPV infections. By prioritizing direct estimation of model transition probabilities from longitudinal data (and limiting reliance on model-fitting techniques that may propagate error when applied to multiple transitions), we aim to reduce the number of assumptions for greater transparency and reliability. We propose this new microsimulation model for critique and discussion, hoping to contribute to models that maximally inform efficient strategies towards global cervical cancer elimination

A feasibility study to prevent falls in older people who are sight impaired: the VIP2UK randomised controlled trial.

BACKGROUND: Published evaluations of successful interventions to prevent falls in people with sight impairment (SI) are limited. The aim of this feasibility study is to optimise the design and investigation of home safety (HS) and home exercise (HE) programmes to prevent falls in older people with SI. METHODS: A community-based feasibility study in north-west England comprising a three-arm randomised controlled trial (RCT) allocated participants to (1) a control group receiving usual care and social visits, (2) an experimental group receiving the HS programme and (3) an experimental group receiving the HS + HE programme. Participants were community-dwelling, aged 65 years and older and sight impaired. Primary outcome data on falls were collected continuously over 6 months. Secondary outcomes on physical activity (self-report and instrumented) and adherence were collected at baseline and 3 and 6 months for HE and at 6 months for the HS programme. Costs for the HS and HS + HE groups were calculated from logs of time spent on home visits, telephone calls and travel. The research assistant and statistician were blinded to group allocation. RESULTS: Altogether, 49 people were recruited over a 9-month period (randomised: 16 to control, 16 to HS, 17 to HS + HE). The interventions were implemented over 6 months by an occupational therapist at a cost per person (pounds sterling, 2011) of £249 (HS) and £674 (HS + HE). Eighty-eight percent (43/49) completed the trial and 6-month follow-up. At 6-month follow-up, 100 % reported partially or completely adhering to HS recommendations but evidence for adherence to HE was equivocal. Although self-reported physical activity increased, instrumented monitoring showed a decrease in walking activity. There were no statistically significant differences in falls between the groups; however, the study was not powered to detect a difference. CONCLUSION: It is feasible and acceptable for an occupational therapist to deliver HS and HE falls prevention programmes to people with SI living independently in the community. Future studies could access Local Authority Registers of people with SI to improve recruitment rates. Further research is required to identify how to improve adherence to HE and to measure changes in physical activity before conducting a definitive RCT. TRIAL REGISTRATION: ISRCTN53433311 , registered on 8 May 2014