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ObjectivesThe Manchester Acute Coronary Syndromes ECG (MACS-ECG) prediction model calculates a score based on objective ECG measurements to give the probability of a non-ST elevation myocardial infarction (NSTEMI). The model showed good performance in the emergency department (ED), but its accuracy in the pre-hospital setting is unknown. We aimed to externally validate MACS-ECG in the pre-hospital environment.MethodsWe undertook a secondary analysis from the Pre-hospital Evaluation of Sensitive Troponin (PRESTO) study, a multi-centre prospective study to validate decision aids in the pre-hospital setting (26 February 2019 to 23 March 2020). Patients with chest pain where the treating paramedic suspected acute coronary syndrome were included. Paramedics collected demographic and historical data and interpreted ECGs contemporaneously (as ‘normal’ or ‘abnormal’). After completing recruitment, we analysed ECGs to calculate the MACS-ECG score, using both a pre-defined threshold and a novel threshold that optimises sensitivity to differentiate AMI from non-AMI. This was compared with subjective ECG interpretation by paramedics. The diagnosis of AMI was adjudicated by two investigators based on serial troponin testing in hospital.ResultsOf 691 participants, 87 had type 1 AMI and 687 had complete data for paramedic ECG interpretation. The MACS-ECG model had a C-index of 0.68 (95% CI: 0.61 to 0.75). At the pre-determined cut-off, MACS-ECG had 2.3% (95% CI: 0.3% to 8.1%) sensitivity, 99.5% (95% CI: 98.6% to 99.9%) specificity, 40.0% (95% CI: 10.2% to 79.3%) positive predictive value (PPV) and 87.6% (87.3% to 88.0%) negative predictive value (NPV). At the optimal threshold for sensitivity, MACS-ECG had 50.6% sensitivity (39.6% to 61.5%), 83.1% specificity (79.9% to 86.0%), 30.1% PPV (24.7% to 36.2%) and 92.1% NPV (90.4% to 93.5%). In comparison, paramedics had a sensitivity of 71.3% (95% CI: 60.8% to 80.5%) with 53.8% (95% CI: 53.8% to 61.8%) specificity, 19.7% (17.2% to 22.45%) PPV and 93.3% (90.8% to 95.1%) NPV.ConclusionNeither MACS-ECG nor paramedic ECG interpretation had a sufficiently high PPV or NPV to ‘rule in’ or ‘rule out’ NSTEMI alone.

Early bystander cardiopulmonary resuscitation, use of defibrillators (including automated external defibrillators) and timely treatment by emergency medical services are known to increase the chances of survival for a patient experiencing an out-of-hospital cardiac arrest (OHCA). However, the impact of the COVID-19 pandemic on this is unclear from examining previous literature. This commentary critically appraises a recent systematic review and meta-analysis, which assessed the effect of the COVID-19 pandemic on prehospital care for OHCA.

Effective triage is critical to ensure patients suffering major trauma are identified and access a pathway to definitive major trauma care, which is typically provided in a major trauma centre as part of an established major trauma system. The prehospital triage of trauma patients often relies upon the use of major trauma triage tools; this commentary critically appraises a recent systematic review that sought to evaluate and compare the accuracy of prehospital triage tools for major trauma.

Purpose The burden of major trauma within the UK is ever increasing. There is a need to establish research priorities within the field. Delphi methodology can be used to develop consensus opinion amongst a group of stakeholders. This can be used to prioritise clinically relevant, patient-centred research questions to guide future funding allocations. The aim of our study was to identify key future research priorities pertaining to the management of major trauma in the UK. Methods A three-phased modified Delphi process was undertaken. Phase 1 involved the submission of research questions by members of the trauma community using an online survey (Phase 1). Phases 2 and 3 involved two consecutive rounds of prioritisation after questions were subdivided into 6 subcategories: Brain Injury, Rehabilitation, Trauma in Older People, Pre-hospital, Interventional, and Miscellaneous (Phases 2 and 3). Cut-off points were agreed by consensus amongst the steering subcommittees. This established a final prioritised list of research questions. Results In phase 1, 201 questions were submitted by 65 stakeholders. After analysis and with consensus achieved, 186 questions were taken forward for prioritisation in phase 2 with 114 included in phase 3. 56 prioritised major trauma research questions across the 6 categories were identified with a clear focus on long-term patient outcomes. Research priorities across the patient pathway from roadside to rehabilitation were deemed of importance. Conclusions Consensus within the major trauma community has identified 56 key research questions across 6 categories. Dissemination of these questions to funding bodies to allow for the development of high-quality research is now required. There is a clear indication for targeted multi-centre multi-disciplinary research in major trauma.

IntroductionTraumatic brain injury (TBI) is a major global health burden that results in disability and loss of health. Identifying those patients who require specialist neuroscience care can be challenging due to the low accuracy of existing prehospital trauma triage tools. Despite the widespread use of decision aids to ‘rule out’ TBI in hospitals, they are not widely used in the prehospital environment. We aim to provide a snapshot of current prehospital practices in the UK, and to explore facilitators and challenges that may be encountered when adopting new tools for decision support.Methods and analysisA mixed-methods study will be conducted using a convergent design approach. In the first phase, we will conduct a national survey of current practice in which every participating ambulance service in the UK will receive an online questionnaire, and only one response is required. In the second phase, semistructured interviews will be conducted to explore the perceptions of ambulance service personnel regarding the implementation of new triage methods that may enhance triage decisions. The survey questions and the interview topic guide were piloted and externally reviewed. Quantitative data will be summarised using descriptive statistics; qualitative data will be analysed thematically.Ethics and disseminationThis study has been approved by the Health Research Authority (REC reference 22/HRA/2035). Our findings may inform the design of future care pathways and research as well as identify challenges and opportunities for future development of prehospital triage tools for patients with suspected TBI. Our findings will be published in peer-reviewed journals, relevant national and international conferences, and will be included in a PhD thesis.

Introduction\ud \ud Prehospital care providers are usually the first responders for patients with traumatic brain injury (TBI). Early identification of patients with TBI enables them to receive trauma centre care, which improves outcomes. Two recent systematic reviews concluded that prehospital triage tools for undifferentiated major trauma have low accuracy. However, neither review focused specifically on patients with suspected TBI. Therefore, we aimed to systematically review the existing evidence on the diagnostic performance of prehospital triage tools for patients with suspected TBI.\ud \ud \ud \ud Methods\ud \ud A comprehensive search of the current literature was conducted using Medline, EMBASE, CINAHL Plus and the Cochrane library (inception to 1st June 2021). We also searched Google Scholar, OpenGrey, pre-prints (MedRxiv) and dissertation databases. We included all studies published in English language evaluating the accuracy of prehospital triage tools for TBI. We assessed methodological quality and risk of bias using a modified Quality Assessment of Diagnostic Studies (QUADAS-2) tool. Two reviewers independently performed searches, screened titles and abstracts and undertook methodological quality assessments. Due to the heterogeneity in the population of interest and prehospital triage tools used, a narrative synthesis was undertaken.\ud \ud \ud \ud Results\ud \ud The initial search identified 1787 articles, of which 8 unique eligible studies met the inclusion criteria (5 retrospective, 2 prospective, 1 mixed). Overall, sensitivity of triage tools studied ranged from 19.8% to 87.9% for TBI identification. Specificity ranged from 41.4% to 94.4%. Two decision tools have been validated more than once: HITS-NS (2 studies, sensitivity 28.3–32.6%, specificity 89.1–94.4%) and the Field Triage Decision Scheme (4 studies, sensitivity 19.8–64.5%, specificity 77.4%-93.1%). Existing tools appear to systematically under-triage older patients.\ud \ud \ud \ud Conclusion\ud \ud Further efforts are needed to improve and optimise prehospital triage tools. Consideration of additional predictors (e.g., biomarkers, clinical decision aids and paramedic judgement) may be required to improve diagnostic accuracy.

Changes in cognition and behaviour occur in approximately 50% of people with amyotrophic lateral sclerosis (ALS), the most common form of motor neurone disease (MND). The aim of this study was to explore current factors influencing the implementation of cognitive and behavioural screening in MND care in the UK. Semi-structured interviews with healthcare professionals working in a range of settings were conducted and data were analysed thematically. In most of the settings included, a pathway to screening and neuropsychological intervention had not yet been established. Factors identified as barriers included: limited number of staff trained to administer screen; limited time available during outpatient clinic hours; and limited or no links with neuropsychological services. Screening was implemented routinely in one setting where there was support from a clinical neuropsychologist working within the MDT. Support from neuropsychological services was suggested to be necessary for interpretation of screening results and advice on intervention.

The reorganization of brain connectivity patterns due to changes in conscious state is poorly understood. The aim of this study is to assess methods for characterizing brain connectivity changes in different sleep stages as compared to wakefulness, and hence identify possible biomarkers of the level of consciousness based on the topography of connectivity networks. Polysomnographic recordings were collected during a sleep experiment from five healthy young subjects. Functional coupling between electroencephalographic (EEG) signals was estimated in different EEG bands with Partial Directed Coherence (PDC) and Directed Coherence (DC), which provide a frequency domain description of directed causal dependencies among time series. Results indicate that in the theta (θ) and alpha (α) bands the number of significant connections increases in the transition from sleep to wakefulness. Moreover connectivity patterns elicited in sleep are dominated by short-range connections, in contrast to long range links connecting distant areas, which are elicited in wakefulness in the α and θ bands. An inversion in the direction of information flow from anterior-posterior to posterior-anterior is noticeable in the transition from sleep to wakefulness in the θ and α bands. The drop of the number of long-range posterior-frontal links in the α band may be a promising indicator for the descent into sleep and perhaps anesthesia.

Whole body vibration (WBV) has been suggested as an alternative form of exercise producing adaptive responses similar to that of resistance training. Very limited information is available on the effects of different vibration parameters on anabolic hormones. In this study, we compared the acute effects of different WBV amplitudes on serum testosterone (T) and insulin growth factor-1 (IGF-1). Nine healthy young recreationally active adult males (age 22 +/- 2 years, height 181 +/- 6.3 cm, weight 77.4 +/- 9.5 kg) voluntarily participated in this randomized controlled (cross-over design) study. The subjects performed 20 sets of 1 min each of WBV exercise in the following conditions: Non-vibration condition (control), low amplitude vibration [low (30 Hz, 1.5 mm peak-to-peak amplitude)] and high amplitude vibration [high (30 Hz, 3 mm peak-to-peak amplitude)]. Blood samples were collected before, after 10 sets, at the end (20th set) and after 24 h of the exercise bout. WBV exercise did not produce significant changes in serum T and IGF-1 either with low or high amplitude when compared with the control condition. The results of this study demonstrate that a single session of WBV exposure with a frequency of 30 Hz and amplitudes of 1.5 and 3 mm does not noticeably alter serum T and IGF-1 levels.

We present intermediate-resolution, phase-resolved spectra of the close-binary systems EC 11575-1845 and V664 Cas, the central star of the planetary nebula HFG 1. Both systems have a very rich emission-line spectrum originating from the face of the cool star, which is irradiated by the hot subdwarf star. The H 1 emission lines are wide, consistent with Stark broadening. These have a complex shape due to strong absorption near the line centre. We report on new spectroscopic orbits for both subdwarf stars, based on radial velocity measurements of their He II lines. The orbits of the heated face of the cool companions were measured from narrow emission lines, and from the wide H I profiles; some differences were found between ions. At phases around 0, absorption lines from the photosphere of the secondary star of V664 Cas are seen. These are used to estimate a spectral type of mid-F to early K, and we report on their radial velocities. Synthetic spectra from the non-local thermodynamic equilibrium model atmospheres were used to fit features in the optical spectrum of the hot subdwarf star of EC 11575-1845, from which we estimate T eff = 105 000 ± 20000 K, logg = 6.7 ± 0.3, log n He /n H = -0.8 ± 0.1. Finally, we consider the most likely range of component masses for these two systems.

A detailed study of the seabed surrounding dredge pits created during the mining of marine aggregate from a small licence off the south coast of the United Kingdom (“Licence Area 122/3”) has been completed. Over 350 km of high-resolution sidescan sonar imagery and 177 sediment samples have been obtained over a study area extending 10 km either side of the dredge zone (representing one full tidal excursion) in order to identify far-field effects on both physical and biological resources of the seabed. The physical results presented here for Area 122/3 clearly show that the physical impact of dredging (without screening) on the seabed is limited to a zone within approximately 300 m downtide of the dredge area. This will generally be within the dredge licence boundary due to operational procedures. There is no evidence of suspended sediments falling to the seabed beyond this zone and causing significant changes, which may be manifested as infilling of small pits by fine sediments, siltation within c...

New data are presented of the post-common-envelope binary VW Pyx and its associated planetary nebula (PN), K 1-2. The central star is found to be a single-lined (and possibly double-lined) spectroscopic binary and is a good candidate for a system in which the main-sequence secondary star is more massive than the subdwarf primary star. The old PN has a high excitation level and a measured electron temperature, To ∼ 17 000 K for an assumed log n e = 2.7 cm - 3 . The so-called 'jets' are found to be lower-ionization regions with T N ∼ 11 000 K and T o ∼ 16 000 K with log n e ∼ 2.5 cm - 3 and with low, but fairly typical, PN abundances. We discuss possible histories for K 1-2 and the jets. However, there are still many unknowns in the study of accretion and jet formation for such PN binary central stars.

Seventy-seven liver transplant candidates were enrolled in a multicenter study in which patients were treated with lamivudine (100 mg daily) without the adjunctive use of hepatitis B immune globulin. Treatment was begun while patients awaited liver transplantation and continued after transplantation. All were hepatitis B surface antigen (HBsAg) positive, and 61% had detectable hepatitis B e antigen (HBeAg) and HBV DNA when treatment was begun. Forty-seven underwent liver transplantation and 30 did not. Median study participation was 38 months (range, 2.7-48.5) in the transplanted patients and 26 months (range, 0.1-37) in the nontransplanted group. Twenty-five of 42 (60%) transplanted patients with 12 or more weeks of posttransplantation follow-up were HBsAg negative at the last study visit. At treatment week 156, 13 of 22 (59%) remained HBsAg negative, and all 9 reinfected patients were HBV-DNA positive before treatment. In the nontransplanted patients, HBeAg was initially detectable in 20 of 27 (74%) but this decreased to 3 of 17 (18%) after 104 weeks of treatment, and significant improvement in biochemical parameters was observed. HBV-DNA polymerase mutants were detected in 15 (21%) and 6 (20%) of the transplanted and nontransplanted patients, respectively. When compared with historical cohorts, lamivudine-treated patients appeared to have improved survival, and transplanted patients had a decrease in the rate of recurrent HBV infection. Lamivudine therapy was partially effective in preventing recurrent HBV infection when given before and after transplantation. Thus, future trials using a combination of HBIg and lamivudine are needed to assess the optimal prophylactic therapy.

We briefly discuss the survey programme we are conducting to detect eclipsing binaries in local group galaxies. Some lightcurves from studies of M31, IC 1613 and NGC 6822 are presented along with details of future work.

This paper describes a comparison between two dynamic methodologies used in the probabilistic risk analysis (PRA) of the Cassini Mission. The main Cassini PRA was performed by Lockheed Martin. A combination of Monte Carlo algorithms and event-tree logic was used to perform the study. Results were validated using an alternative method, the Discrete Dynamic Event Tree (DDET) methodology. Two major conclusions of the paper are 1) performing a dynamic PRA of large scale ‘real-life’ systems is feasible and 2) given the same ground rules and assumptions, two dynamic methodologies would give the same results.

The Alabama State Department of Education (ALSDE) developed a statewide initiative to improve mathematics and science teaching and student achievement in kindergarten through grade 12 (K-12). The Alabama Math, Science, and Technology Initiative (AMSTI) is a two-year intervention intended to better align classroom practices with national and statewide teaching standards — and ultimately to improve student achievement — by providing PD, access to materials and technology, and in-school support for teachers.AMSTI, a schoolwide intervention, was introduced in 20 schools in 2002. Each year since then, the state has rolled out the program to additional schools within its 11 regions. By 2009, about 40% of the state’s 1,518 schools were designated as AMSTI schools. Funding for the program from the state legislature was $46 million in 2009.Given the policy relevance and level of investment in AMSTI, the Regional Educational Laboratory Southeast mounted a longitudinal, cluster randomized controlled trial to determine the effectiveness of AMSTI in grades 4-8, as implemented in five regions in the state. Previous evaluations of the program’s effects on students in K-12 did not use randomized controlled trials. The most recent evaluation (Miron & Maxwell 2007) reported that students in grade 5 in AMSTI schools outperformed students in non-AMSTI schools in math, science, and reading and students in grade 4 in AMSTI schools outperformed their counterparts in non-AMSTI schools in reading only. These evaluations used a study design that compared school-level test scores of AMSTI schools with non-AMSTI schools in the same district but did not establish preintervention comparability. This study’s RCT design improves on previous evaluations because it eliminates selection bias and establishes the preintervention comparability of the two groups.The effect of AMSTI on student achievement in math after one year, as measured by end-of-the-year scores on the Stanford Achievement Test Tenth Edition (SAT 10) math problem solving assessment of students in grades 4–8, was 2.06 scale score units. The difference of 0.05 standard deviation in favor of AMSTI schools is equivalent to a gain of 2 percentile points on the SAT 10 math problem solving assessment for the average control group student had the student received AMSTI. The 0.05 standard deviation is statistically significant but smaller than the effect the research team believed would be detectable by the experiment as designed. Whether this size effect is educationally important is an open question. It may be useful to convert this effect into a more policy-relevant metric — additional student progress measured in days of instruction. In these terms, the average estimated effect of AMSTI was equivalent to 28 days of additional student progress over students receiving conventional math instruction. The effect of AMSTI on student achievement in science, as measured by end-of-the-year scores on the SAT 10 science assessment, required only in grades 5 and 7, was not statistically significant after one year.AMSTI had a positive and statistically significant effect on classroom practices in math and science after one year. Based on multiple surveys in which teachers reported the number of minutes of active learning strategies used during the previous 10-day period, AMSTI math teachers averaged 49.83 more minutes, and AMSTI science teachers averaged 40.07 more minutes than control teachers. These estimated effects are equivalent to 0.47 standard deviation in math and 0.32 standard deviation in science. Although teachers in both the AMSTI and control groups reported using active learning instructional strategies, teachers in AMSTI schools reported spending more time engaged in this type of instruction.The exploratory investigation of the two-year effect of AMSTI on student achievement in science also found a statistically significant result, with a magnitude of 4.00 scale score units. This effect represents a difference of 0.13 standard deviation in favor of AMSTI schools, equivalent to a gain of 5 percentile points for the average control group student had the student received AMSTI for two years.The effect of AMSTI on teacher-reported content knowledge after one year was not statistically significant in either math or science. AMSTI did have a positive and statistically significant effect on student engagement after one year, measured on a 5-point scale ranging from “not engaged” to “fully engaged.” AMSTI teachers were more likely than control teachers to rate their students as achieving higher levels of engagement.An exploration of the differential effects of AMSTI on student achievement for subgroups of students found no statistically significant differential effects on student achievement in mathematics or science based on racial/ethnic minority status, eligibility for free or reduced-price lunch, gender, or pretest level. In reading, however, AMSTI had a statistically significant differential effect for minority and White students of 3.04 scale score points (p

▪ Distributed Simulations of UAS Operational and ATC Environment Scenarios proved to be robust to support the development and testing of onboard UAS Intelligent Analyzer software prototype with: — Multiple UAS Models and airframes — Multiple UAS flight plans and contingency plans — Multiple platforms — Multiple air traffic scenarios ▪ It also proved to be flexible allowing quick adaptation to requirements for extraction of new data types according to physical characteristics and capabilities of various UAS models ▪ It was extendable to software middleware enabling Intelligent Analyzer to be UAS model agnostic ▪ It enabled the smooth hardware-in-the-loop test with an experimental UAS

http://www.connect-world.com/index.php/magazine/emea/item/9877-boundary-blurring-between-telecom-and-the-internet; Convergence has resulted in the blurring of boundaries between the telecom and the Internet worlds. Telecom operators fear the impact of over-the-top services will reduce their networks to dumb pipes. Nevertheless, concepts from the security world suggest one radical solution. Operators could extend their reach by embracing the de-perimeterisation of communication services, allowing the provision of secure services and data on a global basis irrespective of underlying network ownership.

In this paper, the authors report in-vitro tests of an ultrasound system and method of wirelessly transmitting significant amounts of energy into the human body for the purpose of recharging implantable batteries. We demonstrate the complete charging of Li-ion batteries with energy capacities of 35 mA h, 200 mA h, and 600 mA h through several types of animal tissue while keeping the temperature rise of the tissue and piezoelectric receiver below the desired 2°C human safety limit recommended by FDA medical device guidelines. Given these encouraging results, it is logical to conclude that the rapidly growing neurostimulator market is a desirable and appropriate target for introduction of this novel recharging method.

Chapter 1. Introduction: conserved steps in eukaryotic DNA replication: Template Origins Origin recognition Pre-initiation Initiation Elongation Termination Chromatid cohesion and segregation. Chapter 2. AAA and ATPases in loading replication factors: ORC and loading of Cdc6 Cdc6 and loading of MCMs RFC and loading of PCNA. Chapter 3. Ring structures and six fold symmetry in replication: Helicases: MCMs WRN, BLM etc Clamps: PCNA Rad9-Rad1-Hus1. Chapter 4: Polymerization mechanisms: Thermodynamics of polymerization Structural insights into polymerization mechanisms fidelity: Replicative polymerase error rates Enhancing polymerase fidelity by protein interactions. Chapter 5. Molecular hand-off mechanisms in replication: Priming polymerization Polymerase switches Okazaki fragment processing: differential affinities for PCNA Methylation and chromatin modification via molecular hand-off mediated through PCNA? RPA in replication/repair. Chapter 6. Co-ordination of nucleases and helicases: Nucleases in replication: conservation of roles and mechanisms Fen1 and Dna2 at Okazaki fragments Stalled forks, helicases and nucleases - BLM, WRN, Exo1 and others. Chapter 7. The switch from replication to repair (and back): Monitoring DNA integrity Stalled replication forks and replisome stability: impact of lesion type Choosing the right polymerase through PCNA modification Polymerase switching over lesions Restarting stalled forks after repair. Chapter 8: Telomeres and the end replication problem: Structure and stability of telomeres Telomerase: structural and drug inhibition studies ALT pathways of telomere maintenance Telomere length and telomere-specific sister chromatid exchange in replicative senescence. Keeping replicated chromatids together until mitosis: Topoisomerases and separating chromatids SMC proteins, claspins and cohesions Attaching chromatids to the mitotic spindle - the role of ORC. Chapter 10. Chromatin modification during replication: Chromatin context and replication patterns Silenced loci and dormant origins DNA methylation during replication Histone modifications (methylation, acetylation, phosphorylation, ubiquitination - CAF1, SIRT1, SNF2/HDACs etc) Nucleosome positioning in relation to origins. Chapter 11. Mittochondrial DNA replication: Template: copy number, structure and origin DNA pol gamma - mode of action Accessory factors Regulation - autonomous or integrated with cell cycle? Co-ordination with damage sensing and repair. Chapter 12. Archaeal paradigms and parallels for eukaryotic DNA replication: Overview: comparison between archaeal and eukaryotic replication proteins and processes Insights into priming from the structure of the primase core Archaeal MCMs as a model for eukaryotic MCMs Structure of the archaeal preRC and stabilization by GINS Protein interactions with PCNA. Chapter 13. Drug targets in DNA replication: Nuclear replication: ORC, MCMs and GINS - markers or targets? Geminin PCNA (p21) and Ciz Polymerases Telomerase Mitochondrial replication targets Malaria and potential novel drug targets.