Search for magnetic monopoles produced via the Schwinger mechanism.

Electrically charged particles can be created by the decay of strong enough electric fields, a phenomenon known as the Schwinger mechanism1. By electromagnetic duality, a sufficiently strong magnetic field would similarly produce magnetic monopoles, if they exist2. Magnetic monopoles are hypothetical fundamental particles that are predicted by several theories beyond the standard model3-7 but have never been experimentally detected. Searching for the existence of magnetic monopoles via the Schwinger mechanism has not yet been attempted, but it is advantageous, owing to the possibility of calculating its rate through semi-classical techniques without perturbation theory, as well as that the production of the magnetic monopoles should be enhanced by their finite size8,9 and strong coupling to photons2,10. Here we present a search for magnetic monopole production by the Schwinger mechanism in Pb-Pb heavy ion collisions at the Large Hadron Collider, producing the strongest known magnetic fields in the current Universe11. It was conducted by the MoEDAL experiment, whose trapping detectors were exposed to 0.235 per nanobarn, or approximately 1.8 × 109, of Pb-Pb collisions with 5.02-teraelectronvolt center-of-mass energy per collision in November 2018. A superconducting quantum interference device (SQUID) magnetometer scanned the trapping detectors of MoEDAL for the presence of magnetic charge, which would induce a persistent current in the SQUID. Magnetic monopoles with integer Dirac charges of 1, 2 and 3 and masses up to 75 gigaelectronvolts per speed of light squared were excluded by the analysis at the 95% confidence level. This provides a lower mass limit for finite-size magnetic monopoles from a collider search and greatly extends previous mass bounds.

Consensus-Based Guidelines for the Recognition, Diagnosis, and Management of Hemophagocytic Lymphohistiocytosis in Critically Ill Children and Adults.

OBJECTIVE: Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome that often requires critical care support and remains difficult to diagnose. These guidelines are meant to aid in the early recognition, diagnosis, supportive care, and treatment of patients with hemophagocytic lymphohistiocytosis in ICUs. DATA SOURCES: The literature searches were performed with PubMed (MEDLINE). STUDY SELECTION: Keywords and medical subject headings terms for literature search included "macrophage activation syndrome," hemophagocytic lymphohistiocytosis," and "hemophagocytic syndrome." DATA EXTRACTION: The Histiocyte Society developed these consensus recommendations on the basis of published reports and expert opinions with level of evidence provided for each recommendation. They were endorsed by the Society of Critical Care Medicine. DATA SYNTHESIS: Testing for hemophagocytic lymphohistiocytosis should be initiated promptly in all patients admitted to ICUs with an unexplained or disproportionate inflammatory response, especially those with rapid clinical deterioration. Meeting five or more of eight hemophagocytic lymphohistiocytosis 2004 diagnostic criteria serves as a valuable diagnostic tool for hemophagocytic lymphohistiocytosis. Early aggressive critical care interventions are often required to manage the multisystem organ failure associated with hemophagocytic lymphohistiocytosis. Thorough investigation of the underlying triggers of hemophagocytic lymphohistiocytosis, including infections, malignancies, and autoimmune/autoinflammatory diseases, is essential. Early steroid treatment is indicated for patients with familial hemophagocytic lymphohistiocytosis and is often valuable in patients with acquired hemophagocytic lymphohistiocytosis (i.e., secondary hemophagocytic lymphohistiocytosis) without previous therapy, including macrophage activation syndrome (hemophagocytic lymphohistiocytosis secondary to autoimmune/autoinflammatory disease) without persistent or relapsing disease. Steroid treatment should not be delayed, particularly if organ dysfunction is present. In patients with macrophage activation syndrome, whose disease does not sufficiently respond, interleukin-1 inhibition and/or cyclosporine A is recommended. In familial hemophagocytic lymphohistiocytosis and severe, persistent, or relapsing secondary macrophage activation syndrome, the addition of prompt individualized, age-adjusted etoposide treatment is recommended. CONCLUSIONS: Further studies are needed to determine optimal treatment for patients with hemophagocytic lymphohistiocytosis in ICUs, including the use of novel and adjunct therapies.

Physicians' Ratings of their Supervisor's Leadership Behaviors and Their Subsequent Burnout and Satisfaction: A Longitudinal Study.

OBJECTIVE: To evaluate the relationships between immediate supervisors' leadership qualities and the subsequent levels and changes in burnout and satisfaction of supervised physicians 2 years later. PARTICIPANTS AND METHODS: In 2015 and 2017 physicians were asked to complete surveys that included the 9-item Mayo Clinic Leadership Score (range, 9 to 45) assessing their supervisor, an item about satisfaction with the organization, and two items from the Maslach Burnout Inventory. Individual participants' responses to the surveys were linked. RESULTS: Among the 3698 physicians invited to complete both the 2015 and 2017 survey, 1795 (48.5%) responded. The mean composite baseline leadership score was 38.1 (SD, 8.4). Lower mean baseline leadership scores were reported by physicians who had burnout (mean [SD], 36.0 [9.7] vs 39.1 [7.3]; P<.001) 2 years later in comparison to those who did not have burnout 2 years later. In multivariable analysis, higher baseline leadership score of supervisors was independently associated with lower odds of physicians having burnout 2 years later (for each 1-point increase, odds ratio, 0.98; 95% CI, 0.96 to 0.99; P=.002) after adjusting for burnout at baseline, age, gender, length of service, and specialty. Baseline composite leadership score of supervisors was also independently associated with physicians' satisfaction with the organization 2 years later (odds ratio, 1.05; 95% CI, 1.03 to 1.07; P<.0001). CONCLUSION: Physicians' ratings of their immediate supervisors' leadership qualities were associated with their subsequent levels and changes in burnout and satisfaction 2 years later. Additional studies are needed to determine the effect of sharing such scores with immediate supervisors and providing additional leadership training to those with low scores, and if doing so ultimately reduces burnout and improves satisfaction of the supervised physicians.

Characterization of Nonphysician Health Care Workers' Burnout and Subsequent Changes in Work Effort.

Importance: Burnout is a pervasive, unrelenting problem among health care workers (HCWs), with detrimental impact to patients. Data on the impact of burnout on workforce staffing are limited and could help build a financial case for action to address system-level contributors to burnout. Objective: To explore the association of burnout and professional satisfaction with changes in work effort over 24 months in a large cohort of nonphysician HCWs. Design, Setting, and Participants: This longitudinal cohort study was conducted in Rochester, Minnesota; Scottsdale and Phoenix, Arizona; Jacksonville, Florida; and community-based hospitals and health care facilities in the Midwest among nonphysician HCWs who responded to 2 surveys from 2015 to 2017. Analysis was completed November 25, 2020. Exposures: Burnout, as measured by 2 items from the Maslach Burnout Inventory, and professional satisfaction. Main Outcomes and Measures: The main outcome was work effort, as measured in full-time equivalent (FTE) units, recorded in payroll records. Results: Data from 26 280 responders (7293 individuals aged 45-54 years [27.8%]; 20 263 [77.1%] women) were analyzed. A total of 8115 individuals (30.9%) had worked for the organization more than 15 years, and 6595 individuals (25.1%) were nurses. After controlling for sex, age, duration of employment, job category, baseline FTE, and baseline burnout, overall burnout (odds ratio [OR], 1.53; 95% CI, 1.38-1.70; P < .001), high emotional exhaustion at baseline (OR, 1.54; 95% CI, 1.39-1.71; P < .001), and high depersonalization at baseline (OR, 1.40; 95% CI, 1.21-1.62; P < .001) were associated with an HCW reducing their FTE over the following 24 months. Conversely, satisfaction with the organization at baseline was associated with lower likelihood of reduced FTE (OR, 0.73; 95% CI, 0.65-0.83; P < .001). Findings were similar when emotional exhaustion (OR per 1-point increase, 1.12; 95% CI, 1.10-1.16; P < .001), depersonalization (OR per 1-point increase, 1.10; 95% CI, 1.06-1.14; P < .001) and satisfaction with the organization (OR per 1-point increase, 0.83; 95% CI, 0.79-0.88; P < .001) were modeled as continuous measures. Nurses represented the largest group (1026 of 1997 nurses [51.4%]) reducing their FTE over the 24 months. Conclusions and Relevance: This cohort study found that burnout and professional satisfaction of HCWs were associated with subsequent changes in work effort over the following 24 months. These findings highlight the importance of addressing factors contributing to high stress among all HCWs as a workforce retention and cost reduction strategy.

The Association of Current Tobacco Status With Pain and Symptom Severity in Fibromyalgia Patients.

OBJECTIVE: To describe current tobacco use among patients with newly confirmed fibromyalgia and evaluate the association between tobacco use status and severity of reported pain and other fibromyalgia symptoms. PATIENTS AND METHODS: Participants in this study were adult patients (N=1068) with fibromyalgia who met American College of Rheumatology 2010/2011 clinical criteria for fibromyalgia at the time of initial presentation to a Midwest fibromyalgia clinic (June 1, 2018, through May 31, 2019). Multiple linear regression analyses were performed to assess the association of tobacco use status with the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS) scores. Covariates included in these analyses included age, sex, body mass index, depression, opioid medication use, and use of fibromyalgia-specific pharmacotherapy. RESULTS: The patients were largely women (87.0%; n=929), white (87.9%; n=939), and with an average ± SD age of 46.6±13.9 years. The WPI and SSS scores were significantly greater in current tobacco users compared with never tobacco users (WPI effect estimate [EE] = 1.03; 95% CI, 0.30 to 1.76; type III P=.020; SSS EE = 0.47; 95% CI, 0.11 to 0.84; type III P=.036). The WPI score was negatively associated with age (EE = -0.02 per year; 95% CI, -0.03 to -0.001 per year; P=.037) and no use of opioid medication (EE = -1.08; 95% CI, -1.59 to -0.57; P<.001) while positively associated with higher body mass index (EE = 0.03 per 1 kg/m2; 95% CI, 0.001 to 0.06 per kg/m2; P=.04) and higher Patient Health Questionnaire-9 score (EE = 0.12; 95% CI, 0.08 to 0.16; P<.001). CONCLUSION: The results of our study suggest that tobacco use is associated with greater pain and other symptom severity in patients with fibromyalgia. These findings have important clinical and research implications for patients with fibromyalgia who use tobacco and who may benefit from early identification and timely implementation of tobacco cessation treatment to decrease pain and improve overall quality of life.

Frequently Reported Adverse Events With Smoking Cessation Medications: Post Hoc Analysis of a Randomized Trial.

OBJECTIVE: To compare the incidence, severity, and clinical course of frequently reported adverse events (AEs) after treatment with smoking cessation pharmacotherapies. METHODS: This was a multinational, multicenter, post hoc analysis of frequently reported treatment-emergent AEs from a large, phase 4, double-blind, randomized, triple-dummy, placebo-controlled trial (EAGLES), conducted between November 30, 2011, and January 13, 2015, that included smokers with and without psychiatric disorders (N=8144). Treatments were varenicline 1 mg twice daily, bupropion sustained-release 150 mg twice daily, and nicotine patch 21 mg once daily with tapering (12-week treatment, 12-week nontreatment follow-up), with incidence, time to onset, and duration of frequently reported AEs (≥5% of participants in any treatment group) measured. Risk differences for AEs for varenicline and bupropion vs nicotine patch were compared. RESULTS: Across frequently reported AEs, nausea, insomnia, abnormal dreams, anxiety, irritability, dry mouth, fatigue, and application site pruritus differed significantly in active treatment vs placebo groups. Risk differences were as follows: for nausea with varenicline vs nicotine patch, 15.50% (95% CI, 13.20% to 17.80%); for insomnia with bupropion vs nicotine patch, 2.58% (CI, 0.65% to 4.51%); and for abnormal dreams with varenicline and bupropion vs nicotine patch, -2.49% (CI, -4.35% to -0.64%) and -5.60% (CI, -7.27% to -3.93%), respectively. Frequently reported AEs of severe intensity and treatment discontinuation were experienced by less than 1.5% and less than 3% of participants across all groups, respectively. CONCLUSION: Active treatments were well tolerated with comparable AE profiles. Most AEs are not clinically important, and prescribers can reassure patients that those experienced will be manageable. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01456936.

Electronic Cigarette Use Is Not Associated with COVID-19 Diagnosis.

This analysis tested the hypothesis that current e-cigarette use was associated with an increased risk of SARS-CoV-2 infection in patients seeking medical care. E-cigarette and conventional cigarette use were ascertained using a novel electronic health record tool, and COVID-19 diagnosis was ascertained by a validated institutional registry. Logistic regression models were fit to assess whether current e-cigarette use was associated with an increased risk of COVID-19 diagnosis. A total of 69,264 patients who were over the age of 12 years, smoked cigarettes or vaped, and were sought medical care at Mayo Clinic between September 15, 2019 and November 30, 2020 were included. The average age was 51.5 years, 62.1% were females and 86.3% were white; 11.1% were currently smoking cigarettes or using e-cigarettes and 5.1% tested positive for SARS-CoV-2. Patients who used only e-cigarettes were not more likely to have a COVID-19 diagnosis (OR 0.93 [0.69-1.25], P = .628), whereas those who used only cigarettes had a decreased risk (OR 0.43 [0.35-0.53], P < .001). The OR for dual users fell between these 2 values (OR 0.67 [0.49-0.92], P = .013). Although e-cigarettes have the well-documented potential for harm, they do not appear to increase susceptibility to SARS-CoV-2 infection. This result suggests the hypothesis that any beneficial effects of conventional cigarette smoking on susceptibility are not mediated by nicotine.

First Search for Dyons with the Full MoEDAL Trapping Detector in 13 TeV pp Collisions.

The MoEDAL trapping detector consists of approximately 800 kg of aluminum volumes. It was exposed during run 2 of the LHC program to 6.46 fb^{-1} of 13 TeV proton-proton collisions at the LHCb interaction point. Evidence for dyons (particles with electric and magnetic charge) captured in the trapping detector was sought by passing the aluminum volumes comprising the detector through a superconducting quantum interference device (SQUID) magnetometer. The presence of a trapped dyon would be signaled by a persistent current induced in the SQUID magnetometer. On the basis of a Drell-Yan production model, we exclude dyons with a magnetic charge ranging up to five Dirac charges (5g_{D}) and an electric charge up to 200 times the fundamental electric charge for mass limits in the range 870-3120 GeV and also monopoles with magnetic charge up to and including 5g_{D} with mass limits in the range 870-2040 GeV.

Tobacco dependence treatment for special populations: challenges and opportunities

Although smoking rates have declined in most of the countries in the world, there are population groups within these countries whose smoking rates remain significantly higher than the general population. These "forgotten groups" who have not been receiving the needed attention in tobacco control policies and tobacco cessation efforts include people with serious mental illness, substance use disorders, tuberculosis, people living with human immunodeficiency virus (HIV), lesbian-gay-bisexual-transgender-queer people, and pregnant women. A number of steps are needed at the national level in countries where these disparities exist, including modifications to national smoking cessation treatment guidelines that address the special needs of these populations, as well as targeted smoking cessation research, since these populations are often not included in clinical trials. Because of the higher smoking prevalence in these populations, as well as their lower smoking cessation treatment success rates than the general population, more resources are needed if we are to reduce health disparities in these vulnerable populations. Additionally, we believe that more effort should be focused on integrating smoking cessation treatment in the specialized care settings frequented by these subpopulations.

A phase Ib/II and pharmacokinetic study of EP0057 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

BACKGROUND: EP0057 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) of a cyclodextrin-based polymer backbone plus camptothecin, a topoisomerase-1 inhibitor. Prior studies showed efficacy in recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer (EOC). METHODS: This phase Ib/2 trial assessed safety and efficacy of EP0057 Q2W plus weekly paclitaxel in patients with EOC. The recommended phase 2 dose (RP2D) was identified using a 3+3 design. The single-arm phase 2 assessed overall response (ORR) per RECIST 1.1 in patients previously treated with bevacizumab. Secondary objectives included progression free survival (PFS) and duration of response. RESULTS: The RP2D was established as 15 mg/m2 EP0057 Q2W plus 80 mg/m2 paclitaxel administered 3 weeks on/1 week off. Nine patients enrolled on phase 1b, with no DLTs; 21 additional patients enrolled on phase 2. All completed >1 cycle. Median age was 62 (44-76) years, 57% ≥3 prior therapies. For the primary analysis, 6/19 patients with prior bevacizumab had confirmed responses (ORR=31.6% (95% CI: 15.4% to 54.0%)) including one complete response (CR). Median PFS was 5.4 months. Most common grade 3/4 adverse events attributed to treatment were decreased neutrophil count (13, 43%) and anemia (3, 10%). CONCLUSIONS: Although the observed ORR was not statistically better than the historical control rate, EP0057 remains an interesting option for treatment of recurrent EOC. EP0057 exhibits high plasma drug retention, slow clearance, and controlled slow release of CPT from the polymer when administered alone and with paclitaxel. (NCT02389985) 242 words.

Improved Documentation of Electronic Cigarette Use in an Electronic Health Record.

The use of electronic cigarettes (e-cigarettes) can affect patient health and clinical care. However, the current documentation of e-cigarette use in the electronic health records (EHR) is inconsistent. This report outlines how the ambulatory clinical practices of a large U.S. hospital system optimized its electronic health records (EHR) framework to better record e-cigarettes used by patients. The new EHR section for e-cigarette information was implemented for outpatient appointments. During a 30-week evaluation period post-implementation, 638,804 patients (12 yrs and older) completed ambulatory appointments within the health system; of these, the new section contained e-cigarette use information for 37,906 (6%) patients. Among these patients, 1005 (2.7%) were identified as current e-cigarette users (current every day or current some day e-cigarette use), 941 (2.5%) were reported as former e-cigarette users, and 35,960 (94%) had never used e-cigarettes. A separate EHR section to document e-cigarette use is feasible within existing clinical practice models. Utilization of the new section was modest in routine clinical practice, indicating the need for more intensive implementation strategies that emphasize the health effects of e-cigarette use, and how consistent ascertainment could improve clinical practice.

Caudocranial transseptal approach for placement of endocardial left ventricular leads.

Cardiac resynchronization therapy (CRT) is associated with improvement in the quality of life, hospitalization rates, and mortality in patients with left ventricular dysfunction and evidence of the right ventricle-left ventricle (RV-LV) desynchrony. Implant failure rates and patient outcomes have improved with the advent of quadripolar leads, yet alternatives to traditional coronary sinus (CS) LV lead placement is sought for in a subset of advanced heart failure patients with difficult CS anatomy, phrenic nerve stimulation or in nonresponders. Endocardial left ventricular pacing (EnLVP) in chronically anticoagulated patients has been reported as an alternative using different approaches, techniques, and tools with acceptable short and long term adverse events. We present a case of successful EnLVP achieved for CRT using standard techniques and commonly available tools in a patient on chronic direct oral anticoagulation with recurrent heart failure admissions who failed traditional epicardial LV pacing.

Tobacco dependence treatment for special populations: challenges and opportunities.

Although smoking rates have declined in most of the countries in the world, there are population groups within these countries whose smoking rates remain significantly higher than the general population. These "forgotten groups" who have not been receiving the needed attention in tobacco control policies and tobacco cessation efforts include people with serious mental illness, substance use disorders, tuberculosis, people living with human immunodeficiency virus (HIV), lesbian-gay-bisexual-transgender-queer people, and pregnant women. A number of steps are needed at the national level in countries where these disparities exist, including modifications to national smoking cessation treatment guidelines that address the special needs of these populations, as well as targeted smoking cessation research, since these populations are often not included in clinical trials. Because of the higher smoking prevalence in these populations, as well as their lower smoking cessation treatment success rates than the general population, more resources are needed if we are to reduce health disparities in these vulnerable populations. Additionally, we believe that more effort should be focused on integrating smoking cessation treatment in the specialized care settings frequented by these subpopulations.

Design and Pilot Implementation of an Electronic Health Record-Based System to Automatically Refer Cancer Patients to Tobacco Use Treatment.

Continued tobacco use after cancer diagnosis is detrimental to treatment and survivorship. The current reach of evidence-based tobacco treatments in cancer patients is low. As a part of the National Cancer Institute Cancer Center Cessation Initiative, the Mayo Clinic Cancer Center designed an electronic health record (EHR, Epic©)-based process to automatically refer ambulatory oncology patients to tobacco use treatment, regardless of intent to cease tobacco use("opt out"). The referral and patient scheduling, accomplished through a best practice advisory (BPA) directed to staff who room patients, does not require a co-signature from clinicians. This process was piloted for a six-week period starting in July of 2019 at the Division of Medical Oncology, Mayo Clinic, Rochester, MN. All oncology patients who were tobacco users were referred for tobacco treatment by the rooming staff (n = 210). Of these, 150 (71%) had a tobacco treatment appointment scheduled, and 25 (17%) completed their appointment. We conclude that an EHR-based "opt-out" approach to refer patients to tobacco dependence treatment that does not require active involvement by clinicians is feasible within the oncology clinical practice. Further work is needed to increase the proportion of scheduled patients who attend their appointments.

Relationship Between Organizational Leadership and Health Care Employee Burnout and Satisfaction.

OBJECTIVE: To explore the relationship between immediate supervisor leadership behaviors and burnout and professional satisfaction of health care employees. PARTICIPANTS AND METHODS: From October 2 to 20, 2017, we surveyed nonphysician health care employees. The survey included 2 items from the Maslach Burnout Inventory and items on their immediate supervisor leadership behaviors. Logistic regression was performed to evaluate the relationship between the leadership score and the prevalence of burnout and satisfaction after adjusting for age, sex, duration of employment, and job category. Sensitivity analysis was performed using mixed models with a random intercept for work unit to assess the impact of the correlation within work units on burnout and satisfaction with the organization. RESULTS: Of the 57,414 employees surveyed, 39,896 (69.5%) responded and answered the leadership questions. Supervisor scores in each dimension and composite leadership scores correlated with burnout and satisfaction of employees (P<.001 for all). In logistic regression, each 1-point increase in leadership score was associated with a 7% decrease in odds of burnout and an 11% increase in odds of satisfaction (P<.001 for both) of employees. The mean composite leadership score rating of each immediate supervisor correlated with rate of burnout (r=-0.247; P<.001) and the satisfaction with the organization (r=0.416; P<.001) at the work unit level. CONCLUSION: Leadership qualities of immediate supervisors relate to burnout and satisfaction of nonphysician health care employees working in a large organization. Further studies are needed to determine whether strategies to monitor and improve supervisor leadership scores result in reduction in burnout and improved satisfaction among health care employees.

Application of 2016 WHO classification in the diagnosis of paediatric high-grade MYC-negative mature B-cell lymphoma with Burkitt-like morphological features.

AIMS: Historically, there has been no consensus on the diagnostic classification of high-grade B-cell lymphoma (HGBCL) with morphological features of Burkitt lymphoma (BL) but no MYC gene rearrangement (MYC-negative). The 2016 WHO classification of tumours of haematopoietic and lymphoid tissues has shed some light on this field with the modification of the grey-zone lymphoma with features intermediate between BL and diffuse large B-cell lymphoma, and the creation of several new entities. The aim of this study was to investigate how the revised WHO classification affects our practice in diagnosing these lymphomas in children. METHODS: We retrospectively reviewed cases of mature HGBCL diagnosed at our hospital between 2015 and 2018. RESULTS: Among 14 mature HGBCL cases with BL morphological features, 11 showed MYC rearrangement consistent with BL and 3 were MYC-negative. Two MYC-negative cases showed regions of 11q gain and loss by microarray consistent with Burkitt-like lymphoma with 11q aberration (BLL-11q). The third MYC-negative case showed diffuse and strong MUM1 expression, translocation involving 6p25 by chromosome analysis and IRF4 rearrangement by fluorescence in situ hybridisation analysis consistent with large B-cell lymphoma with IRF4 rearrangement (LBL-IRF4). All patients were treated according to applicable chemotherapeutic protocols and achieved remission. CONCLUSIONS: BLL-11q and LBL-IRF4, two newly defined entities, should be considered in paediatric MYC-negative mature HGBCL cases. Accurate diagnosis needs careful histopathological examination and proper cytogenetic testing. Since they have unique cytogenetic features, specific treatments for them may emerge in the future. Therefore, accurate diagnosis based on the 2016 WHO classification is clinically significant.