Minimally invasive, patient specific, beat-by-beat estimation of left ventricular time varying elastance.

peer reviewedBACKGROUND: The aim of this paper was to establish a minimally invasive method for deriving the left ventricular time varying elastance (TVE) curve beat-by-beat, the monitoring of which's inter-beat evolution could add significant new data and insight to improve diagnosis and treatment. The method developed uses the clinically available inputs of aortic pressure, heart rate and baseline end-systolic volume (via echocardiography) to determine the outputs of left ventricular pressure, volume and dead space volume, and thus the TVE curve. This approach avoids directly assuming the shape of the TVE curve, allowing more effective capture of intra- and inter-patient variability. RESULTS: The resulting TVE curve was experimentally validated against the TVE curve as derived from experimentally measured left ventricular pressure and volume in animal models, a data set encompassing 46,318 heartbeats across 5 Pietrain pigs. This simulated TVE curve was able to effectively approximate the measured TVE curve, with an overall median absolute error of 11.4% and overall median signed error of -2.5%. CONCLUSIONS: The use of clinically available inputs means there is potential for real-time implementation of the method at the patient bedside. Thus the method could be used to provide additional, patient specific information on intra- and inter-beat variation in heart function

Screening and brief intervention delivery in the workplace to reduce alcohol-related harm:A pilot randomized controlled trial

Aim: To explore the feasibility and cost effectiveness of screening and delivery of a brief intervention for hazardous drinking employees. Methods: A pilot randomised controlled trial of a brief intervention delivered by an Occupational Health nurse versus no delivery of brief intervention (control group) conducted in a Local Authority Council (LCA) in the United Kingdom. Changes in quality of life and economic indicators were measured by the EQ-5D. Results: 627 employees were screened of whom 163 (26.01%) fulfilled the inclusion criteria with a total of 57 (35%) agreeing to participate. No significant differences were found between the groups for baseline demographics or levels/patterns of alcohol consumption. A statistically significant effect was found in the mean AUDIT scores over time (F = 8.96, p = 0.004) but not for group (F = 0.017, p = 0.896), and no significant interaction was found (F = 0.148, p = 0.702). The cost of each intervention was calculated at £12.48, the difference in service costs was calculated at £344.50 per person; that is there was a net saving of health and other care costs in the intervention group compared to the control group. The QALYs fell in both intervention and control groups, the difference −0.002 − (−0.010) yields a net advantage of the intervention of 0.008 QALYs. Conclusion: The main results from this pilot study suggest that alcohol brief interventions delivered in the workplace may offer the potential to reduce alcohol-related harm and save public sector resources. A fully powered multi-centre trial is warranted to contribute to the current evidence base and explore further the potential of alcohol brief interventions in the workplace. In a full trial the recruitment method may need to be re-considered

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Capitalism and Earth System Governance: An Ecological Marxist Approach

Growing recognition of the Anthropocene era has led to a chorus of calls for Earth System Governance (ESG). Advocates argue that humanity's newfound sociotechnical powers require institutional transformations at all scales of governance to wield these powers with wisdom and foresight. Critics, on the other hand, fear that these initiatives embody a technocratic impulse that aims to subject the planet to expert management without addressing the political-economic roots of the earth system crisis. This article proposes a more affirmative engagement with existing approaches to ESG while also building on these critiques. While advocates of ESG typically ignore the capitalistic roots of the earth system crisis and propose tepid reforms that risk authoritarian expressions, their critics also have yet to systematically consider the potential for more democratic and postcapitalist forms of ESG. In response, I propose an ecological Marxist approach based on a structural analysis of capitalism as the primary driver of the earth system crisis and an "ecosocialist" vision of ESG that subordinates the market to democratic planning at multiple scales. I argue that an ecological Marxist perspective is needed to foreground the structural political-economic constraints on earth system stability, though existing approaches to ESG can in turn inform ecosocialist strategies for global institutional design and democratization

JET machine operations in T&D-T

JET, the world's largest operating tokamak with unique Be/W wall and tritium handling capability, completed a Deuterium-Tritium (D-T) campaign in 2021 (Maggi et al 29th Fusion Energy Conf.) following a decade of preparatory experiments, dedicated enhancements, technical rehearsals and training (Horton et al 2016 Fusion Eng. Des. 109-111 925). Operation with tritium raises significant technical, safety and scientific challenges not encountered in standard protium or deuterium operation. This contribution describes the tritium operational requirements, pulses and technical preparations, new operating procedures, lessons learned and details on the achieved operational availability and performance. The preparation and execution of the recent JET tritium experiments benefitted from the previous experience in 1991 (Preliminary Tritium Experiment), 1997 (DTE1 campaign) and 2003 (Trace Tritium Campaigns) and consisted of the following five phases: technical rehearsals and scenario preparation, tritium commissioning, 100% tritium campaign, D-T campaign (DTE2), tritium clean-up. Following the clean-up JET resumed normal operation and is currently undertaking a further D-T campaign (DTE3)

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707