Cassini in situ observations of long duration magnetic reconnection in Saturn’s magnetotail

Magnetic reconnection is a fundamental process in solar system and astrophysical plasmas, through which stored magnetic energy associated with current sheets is converted into thermal, kinetic and wave energy1, 2, 3, 4. Magnetic reconnection is also thought to be a key process involved in shedding internally produced plasma from the giant magnetospheres at Jupiter and Saturn through topological reconfiguration of the magnetic field5, 6. The region where magnetic fields reconnect is known as the diffusion region and in this letter we report on the first encounter of the Cassini spacecraft with a diffusion region in Saturn’s magnetotail. The data also show evidence of magnetic reconnection over a period of 19?h revealing that reconnection can, in fact, act for prolonged intervals in a rapidly rotating magnetosphere. We show that reconnection can be a significant pathway for internal plasma loss at Saturn6. This counters the view of reconnection as a transient method of internal plasma loss at Saturn5, 7. These results, although directly relating to the magnetosphere of Saturn, have applications in the understanding of other rapidly rotating magnetospheres, including that of Jupiter and other astrophysical bodies

Ice giant systems: the scientific potential of orbital missions to Uranus and Neptune

Uranus and Neptune, and their diverse satellite and ring systems, represent the least explored environments of our Solar System, and yet may provide the archetype for the most common outcome of planetary formation throughout our galaxy. Ice Giants will be the last remaining class of Solar System planet to have a dedicated orbital explorer, and international efforts are under way to realise such an ambitious mission in the coming decades. In 2019, the European Space Agency released a call for scientific themes for its strategic science planning process for the 2030s and 2040s, known as Voyage 2050. We used this opportunity to review our present-day knowledge of the Uranus and Neptune systems, producing a revised and updated set of scientific questions and motivations for their exploration. This review article describes how such a mission could explore their origins, ice-rich interiors, dynamic atmospheres, unique magnetospheres, and myriad icy satellites, to address questions at the heart of modern planetary science. These two worlds are superb examples of how planets with shared origins can exhibit remarkably different evolutionary paths: Neptune as the archetype for Ice Giants, whereas Uranus may be atypical. Exploring Uranus' natural satellites and Neptune's captured moon Triton could reveal how Ocean Worlds form and remain active, redefining the extent of the habitable zone in our Solar System. For these reasons and more, we advocate that an Ice Giant System explorer should become a strategic cornerstone mission within ESA's Voyage 2050 programme, in partnership with international collaborators, and targeting launch opportunities in the early 2030s

Outcome of major cardiac injuries at a Canadian trauma center

BACKGROUND: Canadian trauma units have relatively little experience with major cardiac trauma (disruption of a cardiac chamber) so injury outcome may not be comparable to that reported from other countries. We compared our outcomes to those of other centers. METHODS: Records of patients suffering major cardiac trauma over a nine-year period were reviewed. Factors predictive of outcome were analyzed. RESULTS: Twenty-seven patients (11 blunt and 16 penetrating) with major cardiac trauma were evaluated. Injury severity scores (ISS) were similar for blunt (49.6 ± 16.6) and penetrating (39.5 ± 21.6, p = 0.20) injuries. Five of 11 blunt trauma patients, and 9 of 16 penetrating trauma patients, had detectable vital signs on hospital arrival (p = 0.43). Ten patients underwent emergency department thoracotomy and 11 patients had cardiac repair in the operating theatre. Eleven patients survived and 16 died. Survivors had a lower ISS (33.7 ± 15.4) than non-survivors (50.4 ± 20.4; p = 0.03). Two of 11 blunt trauma patients and 9 of 16 penetrating trauma patients survived (p = 0.06). Eleven of 14 patients with detectable vital signs survived; all 13 without detectable vital signs died (p = 0.00003). Ten of eleven patients treated in the operating theatre survived, while only one of the other 16 patients survived (p = 0.00002). CONCLUSIONS: Patients with major cardiac injuries and detectable vital signs on hospital arrival can be salvaged by prompt surgical intervention in the operating theatre. Major cardiac injuries are infrequently encountered at our center but patient survival is comparable to that reported from trauma units in other countries

Teprasiran, a Small Interfering RNA, for the Prevention of Acute Kidney Injury in High-Risk Patients Undergoing Cardiac Surgery

Background: Acute kidney injury (AKI) affects up to 30% of patients undergoing cardiac surgery, leading to increased in-hospital and long-term morbidity and mortality. Teprasiran is a novel small interfering RNA that temporarily inhibits p53-mediated cell death that underlies AKI. Methods: This prospective, multicenter, double-blind, randomized, controlled phase 2 trial evaluated the efficacy and safety of a single 10 mg/kg dose of teprasiran versus placebo (1:1), in reducing the incidence, severity, and duration of AKI after cardiac surgery in high-risk patients. The primary end point was the proportion of patients who developed AKI determined by serum creatinine by postoperative day 5. Other end points included AKI severity and duration using various prespecified criteria. To inform future clinical development, a composite end point of major adverse kidney events at day 90, including death, renal replacement therapy, and ≥25% reduction of estimated glomerular filtration rate was assessed. Both serum creatinine and serum cystatin-C were used for estimated glomerular filtration rate assessments. Results: A total of 360 patients were randomly assigned in 41 centers; 341 dosed patients were 73±7.5 years of age (mean±SD), 72% were men, and median European System for Cardiac Operative Risk Evaluation score was 2.6%. Demographics and surgical parameters were similar between groups. AKI incidence was 37% for teprasiran- versus 50% for placebo-treated patients, a 12.8% absolute risk reduction, P=0.02; odds ratio, 0.58 (95% CI, 0.37-0.92). AKI severity and duration were also improved with teprasiran: 2.5% of teprasiran- versus 6.7% of placebo-treated patients had grade 3 AKI; 7% teprasiran- versus 13% placebo-treated patients had AKI lasting for 5 days. No significant difference was observed for the major adverse kidney events at day 90 composite in the overall population. No safety issues were identified with teprasiran treatment. Conclusions: The incidence, severity, and duration of early AKI in high-risk patients undergoing cardiac surgery were significantly reduced after teprasiran administration. A phase 3 study with a major adverse kidney event at day 90 primary outcome that has recently completed enrollment was designed on the basis of these findings (NCT03510897)

Examination of psychological risk factors for chronic pain following cardiac surgery: protocol for a prospective observational study

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. INTRODUCTION: Approximately 400 000 Americans and 36 000 Canadians undergo cardiac surgery annually, and up to 56% will develop chronic postsurgical pain (CPSP). The primary aim of this study is to explore the association of pain-related beliefs and gender-based pain expectations on the development of CPSP. Secondary goals are to: (A) explore risk factors for poor functional status and patient-level cost of illness from a societal perspective up to 12 months following cardiac surgery; and (B) determine the impact of CPSP on quality-adjusted life years (QALYs) borne by cardiac surgery, in addition to the incremental cost for one additional QALY gained, among those who develop CPSP compared with those who do not. METHODS AND ANALYSES: In this prospective cohort study, 1250 adults undergoing cardiac surgery, including coronary artery bypass grafting and open-heart procedures, will be recruited over a 3-year period. Putative risk factors for CPSP will be captured prior to surgery, at postoperative day 3 (in hospital) and day 30 (at home). Outcome data will be collected via telephone interview at 6-month and 12-month follow-up. We will employ generalised estimating equations to model the primary (CPSP) and secondary outcomes (function and cost) while adjusting for prespecified model covariates. QALYs will be estimated by converting data from the Short Form-12 (version 2) to a utility score. ETHICS AND DISSEMINATION: This protocol has been approved by the responsible bodies at each of the hospital sites, and study enrolment began May 2015. We will disseminate our results through CardiacPain.Net, a web-based knowledge dissemination platform, presentation at international conferences and publications in scientific journals. TRIAL REGISTRATION NUMBER: NCT01842568

Rapid porosity and permeability changes of calcareous sandstone due to CO₂-enriched brine injection

Reservoir injectivity and storage capacity are the main constraints for geologic CO2 sequestration, subject to safety and economic considerations. Brine acidification following CO2 dissolution leads to fluid-rock interactions that alter porosity and permeability, thereby affecting reservoir storage capacity and injectivity. Thus, we determined how efficiently CO2-enriched brines could dissolve calcite in sandstone cores and how this affects the petrophysical properties. During computerized tomography monitored flow-through reactor experiments, calcite dissolved at a rate largely determined by the rate of acid supply, even at high flow velocities which would be typical near an injection well. The porosity increase was accompanied by a significant increase in rock permeability, larger than that predicted using classical porosity-permeability models. This chemically driven petrophysical change might be optimized using injection parameters to maximize injectivity and storage

Durable response with single-agent acalabrutinib in patients with relapsed or refractory mantle cell lymphoma

Bruton tyrosine kinase (BTK) inhibitors have greatly improved the spectrum of treatment options in mantle cell lymphoma (MCL) [1–4]. Acalabrutinib is a highly selective, orally administered, and potent BTK inhibitor with limited off-target activity [5]. Acalabrutinib was approved in 2017 by the US Food and Drug Administration for the treatment of relapsed/refractory MCL based on clinical data from the open-label, multicenter, phase 2 ACE-LY-004 study of acalabrutinib 100 mg twice daily [1]. Here, we present updated results from the ACE-LY-004 study after a median 26-month follow-up. Eligibility criteria and study design were published previously (Supplementary methods) [1]. Analysis of minimal residual disease (MRD) was conducted after complete response (CR) or partial response (PR) was achieved using the quantitative ClonoSEQ next-generation sequencing (5 × 10−6 ) assay (Adpative Biotechnologies, Seattle, WA, USA) in consenting patients with available paired archival tumor and whole blood samples. Data are updated as of February 12, 2018

Influence of Baseline Characteristics, Operative Conduct, and Postoperative Course on 30-Day Outcomes of Coronary Artery Bypass Grafting Among Patients With Left Ventricular Dysfunction Results From the Surgical Treatment for Ischemic Heart Failure (STICH) Trial

Background Patients with severe left ventricular dysfunction, ischemic heart failure, and coronary artery disease suitable for coronary artery bypass grafting (CABG) are at higher risk for surgical morbidity and mortality. Paradoxically, those patients with the most severe coronary artery disease and ventricular dysfunction who derive the greatest clinical benefit from CABG are also at the greatest operative risk, which makes decision making regarding whether to proceed to surgery difficult in such patients. To better inform such decision making, we analyzed the Surgical Treatment for Ischemic Heart Failure (STICH) CABG population for detailed information on perioperative risk and outcomes. Methods and Results In both STICH trials (hypotheses), 2136 patients with a left ventricular ejection fraction of 35% and coronary artery disease were allocated to medical therapy, CABG plus medical therapy, or CABG with surgical ventricular reconstruction. Relationships of baseline characteristics and operative conduct with morbidity and mortality at 30 days were evaluated. There were a total of 1460 patients randomized to and receiving surgery, and 346 (approximate to 25%) of these high-risk patients developed a severe complication within 30 days. Worsening renal insufficiency, cardiac arrest with cardiopulmonary resuscitation, and ventricular arrhythmias were the most frequent complications and those most commonly associated with death. Mortality at 30 days was 5.1% and was generally preceded by a serious complication (65 of 74 deaths). Left ventricular size, renal dysfunction, advanced age, and atrial fibrillation/flutter were significant preoperative predictors of mortality within 30 days. Cardiopulmonary bypass time was the only independent surgical variable predictive of 30-day mortality. Conclusions CABG can be performed with relatively low 30-day mortality in patients with left ventricular dysfunction. Serious postoperative complications occurred in nearly 1 in 4 patients and were associated with mortality. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00023595