Extreme Ultraviolet Explorer (EUVE): Emergency support

The Extreme Ultraviolet Explorer (EUVE) will conduct a survey of the entire celestial sphere in the extreme ultraviolet (UV) spectrum, 100 to 1000 angstrom units. This survey will be accomplished using four grazing incidence telescopes mounted on a spinning spacecraft whose spin axis is along the Sun line. Data is taken only when the spacecraft is in the Earth's shadow. The EUVE will be placed in a near circular orbit by a Delta expendable launch vehicle. The design orbit is circular at an altitude of 550 km by 28.5 degrees for a period of 96 minutes. The EUVE will be flown on a standardized Explorer Platform (EP) which will be reused for followup Explorer missions. Coverage will be provided by the Deep Space Network (DSN) for EUVE emergencies that would prevent communications via the normal channels of the Tracking and Data Relay Satellite System (TDRSS). Emergency support will be provided by the 26-meter subnet. Data is presented in tabular form for DSN support, frequency assignments, telemetry, and command

The Nature of Leukaemia

The classification of leukaemia as a pathological process has proved difficult, as it exhibits features of more than one of the main disease types. It is most widely recognised as a neoplastic disease, but it does not behave entirely in this way ; the remitting and relapsing course of the chronic leukeamias is not at all typical of the malignant diseases. In some respects, leukaemia resembles a profound metabolic disturbance, while its presentation and course in the acute form are similar to those of a fulminating infection. This last comparison is rather difficult since severe local infection and even septicaemia are sometimes found in association with the acute types of leukaemia. Although a viral agent has been established as causative in avian leukaemias, no micro-organism has yet been shown to be associated with the human forms of the disease. The uncontrolled proliferation of primitive cells of the leucopoietic system and the capacity of these cells to infiltrate various tissues with an eventual fatal termination is in keeping with a neoplastic process and may represent an extreme form, in company with such conditions as diffuse myelomatosis. However, local deposits of leukaemic tissue such as chloroma are not as common as the local type of myeloma

Suborbital Payload Testing Aboard Level 3 Rocket Research Platform

Embry-Riddle Aeronautical University (ERAU) has launched several suborbital scientific payloads aboard Blue Origin’s New Shepard in 2017 and 2019. Students continue gaining hands-on experience in rocket design and construction, and payload integration and testing of future and more mature payloads to be launched into space. A Level 3 Rocket is being designed and developed at ERAU to serve as a scaled-down model research platform for launching and testing of payloads that will be later flown in commercial suborbital platforms such as Blue Origin’s New Shepard and PLD space Miura 1 rockets. Computer simulations were conducted to calculate the key parameters such as flight trajectory profiles, stability and flight velocities for different rocket motors configurations. A preliminary design of the rocket was developed using Computer-Aided Design (CAD) software. The rocket will accommodate multiple payloads (Cubesats, NanoLabs, TubeSats) designed and developed in the Payload Applied, Technology and Operations (PATO) laboratory. The rocket will be primarily constructed of carbon fiber composite as it has a high strength to weight ratio. These simulations are used to select a suitable motor for the rocket according to the flight requirements and landing restrictions. This prospective Level 3 Rocket is referred to as Suborbital Technology Experimental Vehicle for Exploration (STEVE). Rocket procedures and results from the design, simulation, construction and assembly will be presented

Establishing intra- and inter-rater agreement of the Face, Legs, Activity, Cry, Consolability scale for evaluating pain in toddlers during immunization

BACKGROUND: The Face, Legs, Activity, Cry, Consolability (FLACC) scale is a five-item tool that was developed to assess postoperative pain in young children. The tool is frequently used as an outcome measure in studies investigating acute procedural pain in young children; however, there are limited published psychometric data in this context. OBJECTIVE: To establish inter-rater and intrarater agreement of the FLACC scale in toddlers during immunization. METHODS: Participants comprised a convenience sample of toddlers recruited from an immunization drop-in service, who were part of a larger pilot randomized controlled trial. Toddlers were video- and audiotaped during immunization procedures. The first rater scored each video twice in random order over a period of three weeks (intrarater agreement), while the second rater scored each video once and was blinded to the first rater\u27s scores (inter-rater agreement). The FLACC scale was scored at four timepoints throughout the procedure. Intraclass correlation coefficients were used to assess agreement of the FLACC scale. RESULTS: Thirty toddlers between 12 and 18 months of age were recruited, and video data were available for 29. Intrarater agreement coefficients were 0.88 at baseline, 0.97 at insertion of first needle, and 0.80 and 0.81 at 15 s and 30 s following the final injection, respectively. Inter-rater coefficients were 0.40 at baseline, 0.95 at insertion of first needle, and 0.81 and 0.78 at 15 s and 30 s following the final injection, respectively. CONCLUSIONS: The FLACC scale has sufficient agreement in assessing pain in toddlers during immunizations, especially during the most painful periods of the procedure

Multicentre, randomised clinical trial of paediatric concussion assessment of rest and exertion (PedCARE): a study to determine when to resume physical activities following concussion in children.

INTRODUCTION: Rest until symptom-free, followed by a progressive stepwise return to activities, is often prescribed in the management of paediatric concussions. Recent evidence suggests prolonged rest may hinder recovery, and early resumption of physical activity may be associated with more rapid recovery postconcussion. The primary objective is to determine whether the early reintroduction of non-contact physical activity beginning 72 hours postinjury reduces postconcussive symptoms at 2 weeks in children following an acute concussion as compared with a rest until asymptomatic protocol. METHODS AND ANALYSIS: This study is a randomised clinical trial across three Canadian academic paediatric emergency departments. A total of 350 participants, aged 10-17.99 years, who present within 48 hours of an acute concussion, will be recruited and randomly assigned to either the study intervention protocol (resumption of physical activity 72 hours postconcussion even if experiencing symptoms) or physical rest until fully asymptomatic. Participants will document their daily physical and cognitive activities. Follow-up questionnaires will be completed at 1, 2 and 4 weeks postinjury. Compliance with the intervention will be measured using an accelerometer (24 hours/day for 14 days). Symptoms will be measured using the validated Health and Behaviour Inventory. A linear multivariable model, adjusting for site and prognostically important covariates, will be tested to determine differences between groups. The proposed protocol adheres to the RCT-CONSORT guidelines. DISCUSSION: This trial will determine if early resumption of non-contact physical activity following concussion reduces the burden of concussion and will provide healthcare professionals with the evidence by which to recommend the best timing of reintroducing physical activities

Investing in updating: how do conclusions change when Cochrane systematic reviews are updated?

BACKGROUND: Cochrane systematic reviews aim to provide readers with the most up-to-date evidence on the effects of healthcare interventions. The policy of updating Cochrane reviews every two years consumes valuable time and resources and may not be appropriate for all reviews. The objective of this study was to examine the effect of updating Cochrane systematic reviews over a four year period. METHODS: This descriptive study examined all completed systematic reviews in the Cochrane Database of Systematic Reviews (CDSR) Issue 2, 1998. The latest version of each of these reviews was then identified in CDSR Issue 2, 2002 and changes in the review were described. For reviews that were updated within this time period and had additional studies, we determined whether their conclusion had changed and if there were factors that were predictive of this change. RESULTS: A total of 377 complete reviews were published in CDSR Issue 2, 1998. In Issue 2, 2002, 14 of these reviews were withdrawn and one was split, leaving 362 reviews to examine for the purpose of this study. Of these reviews, 254 (70%) were updated. Of these updated reviews, 23 (9%) had a change in conclusion. Both an increase in precision and a change in statistical significance of the primary outcome were predictive of a change in conclusion of the review. CONCLUSION: The concerns around a lack of updating for some reviews may not be justified considering the small proportion of updated reviews that resulted in a changed conclusion. A priority-setting approach to the updating of Cochrane systematic reviews may be more appropriate than a time-based approach. Updating all reviews as frequently as every two years may not be necessary, however some reviews may need to be updated more often than every two years

Effects of prenatal exercise on fetal heart rate, umbilical and uterine blood flow: a systematic review and meta-analysis

Objective To perform a systematic review and meta-analysis examining the influence of acute and chronic prenatal exercise on fetal heart rate (FHR) and umbilical and uterine blood flow metrics. Design Systematic review with random-effects meta-analysis and meta-regression. Data sources Online databases were searched up to 6 January 2017. Study eligibility criteria Studies of all designs were included (except case studies) if published in English, Spanish or French, and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone [“exercise-only”] or in combination with other intervention components [eg, dietary; “exercise + co-intervention”]), comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and outcomes (FHR, beats per minute (bpm); uterine and umbilical blood flow metrics (systolic:diastolic (S/D) ratio; Pulsatility Index (PI); Resistance Index (RI); blood flow, mL/min; and blood velocity, cm/s)). Results ‘Very low’ to ‘moderate’ quality evidence from 91 unique studies (n=4641 women) were included. Overall, FHR increased during (mean difference (MD)=6.35bpm; 95% CI 2.30 to 10.41, I2=95%, p=0.002) and following acute exercise (MD=4.05; 95% CI 2.98 to 5.12, I2=83%, p\u3c0.00001). The incidence of fetal bradycardia was low at rest and unchanged with acute exercise. There were no significant changes in umbilical or uterine S/D, PI, RI, blood flow or blood velocity during or following acute exercise sessions. Chronic exercise decreased resting FHR and the umbilical artery S/D, PI and RI at rest. Conclusion Acute and chronic prenatal exercise do not adversely impact FHR or uteroplacental blood flow metrics

Requirements for Efficient Proteolytic Cleavage of Prelamin A by ZMPSTE24

The proteolytic maturation of the nuclear protein lamin A by the zinc metalloprotease ZMPSTE24 is critical for human health. The lamin A precursor, prelamin A, undergoes a multi-step maturation process that includes CAAX processing (farnesylation, proteolysis and carboxylmethylation of the C-terminal CAAX motif), followed by ZMPSTE24-mediated cleavage of the last 15 amino acids, including the modified C-terminus. Failure to cleave the prelamin A "tail", due to mutations in either prelamin A or ZMPSTE24, results in a permanently prenylated form of prelamin A that underlies the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS) and related progeroid disorders.Here we have investigated the features of the prelamin A substrate that are required for efficient cleavage by ZMPSTE24. We find that the C-terminal 41 amino acids of prelamin A contain sufficient context to allow cleavage of the tail by ZMPSTE24. We have identified several mutations in amino acids immediately surrounding the cleavage site (between Y646 and L647) that interfere with efficient cleavage of the prelamin A tail; these mutations include R644C, L648A and N650A, in addition to the previously reported L647R. Our data suggests that 9 of the 15 residues within the cleaved tail that lie immediately upstream of the CAAX motif are not critical for ZMPSTE24-mediated cleavage, as they can be replaced by the 9 amino acid HA epitope. However, duplication of the same 9 amino acids (to increase the distance between the prenyl group and the cleavage site) impairs the ability of ZMPSTE24 to cleave prelamin A.Our data reveals amino acid preferences flanking the ZMPSTE24 cleavage site of prelamin A and suggests that spacing from the farnesyl-cysteine to the cleavage site is important for optimal ZMPSTE24 cleavage. These studies begin to elucidate the substrate requirements of an enzyme activity critical to human health and longevity

Identifying null meta-analyses that are ripe for updating

BACKGROUND: As an increasingly large number of meta-analyses are published, quantitative methods are needed to help clinicians and systematic review teams determine when meta-analyses are not up to date. METHODS: We propose new methods for determining when non-significant meta-analytic results might be overturned, based on a prediction of the number of participants required in new studies. To guide decision making, we introduce the "new participant ratio", the ratio of the actual number of participants in new studies to the predicted number required to obtain statistical significance. A simulation study was conducted to study the performance of our methods and a real meta-analysis provides further evidence. RESULTS: In our three simulation configurations, our diagnostic test for determining whether a meta-analysis is out of date had sensitivity of 55%, 62%, and 49% with corresponding specificity of 85%, 80%, and 90% respectively. CONCLUSIONS: Simulations suggest that our methods are able to detect out-of-date meta-analyses. These quick and approximate methods show promise for use by systematic review teams to help decide whether to commit the considerable resources required to update a meta-analysis. Further investigation and evaluation of the methods is required before they can be recommended for general use