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OBJECTIVE Digital subtraction angiography (DSA) is commonly performed after pial synangiosis surgery for pediatric moyamoya disease to assess the degree of neovascularization. However, angiography is invasive, and the risk of ionizing radiation is a concern in children. In this study, the authors aimed to identify whether arterial spin labeling (ASL) can predict postoperative angiogram grading. In addition, they sought to determine whether patients who underwent ASL imaging without DSA had similar postoperative outcomes when compared with patients who received ASL imaging and postoperative DSA. METHODS The medical records of pediatric patients who underwent pial synangiosis for moyamoya disease at a quaternary children’s hospital were reviewed during a 10-year period. ASL-only and ASL+DSA cohorts were analyzed. The frequency of preoperative and postoperative symptoms was analyzed within each cohort. Three neuroradiologists assigned a visual ASL grade for each patient indicating the change from the preoperative to postoperative ASL perfusion sequences. A postoperative neovascularization grade was also assigned for patients who underwent DSA. RESULTS Overall, 21 hemispheres of 14 patients with ASL only and 14 hemispheres of 8 patients with ASL+DSA were analyzed. The groups had similar rates of MRI evidence of acute or chronic stroke preoperatively (61.9% in the ASL-only group and 64.3% in the ASL+DSA group). In the entire cohort, transient ischemic attack (TIA) (p = 0.027), TIA composite (TIA or unexplained neurological symptoms; p = 0.0006), chronic headaches (p = 0.035), aphasia (p = 0.019), and weakness (p = 0.001) all had decreased frequency after intervention. The authors found a positive association between revascularization observed on DSA and the visual ASL grading (p = 0.048). The visual ASL grades in patients with an angiogram indicating robust neovascularization demonstrated improved perfusion when compared with the ASL grades of patients with a poor neovascularization. CONCLUSIONS Noninvasive ASL perfusion imaging had an association with postoperative DSA neoangiogenesis following pial synangiosis surgery in children. There were no significant postoperative stroke differences between the ASL-only and ASL+DSA cohorts. Both cohorts demonstrated significant improvement in preoperative symptoms after surgery. Further study in larger cohorts is necessary to determine whether the results of this study are validated in order to circumvent the invasive catheter angiogram.

Aims Surveillance imaging is often used to detect remodelling, a change in cardiac geometry, and/or function; however, there are limited data in patients with chronic heart failure (HF). We sought to characterize cardiac remodelling in patients with chronic HF and evaluate its association with outcome. Methods and results A prospective cohort of patients at risk for HF or with chronic HF underwent cardiac magnetic resonance (CMR) at baseline and 1 year. Ventricular function, volumes, mass, left atrial volume, global longitudinal strain, and myocardial scar were measured. The primary outcome was a composite of death or cardiovascular hospitalization up to 5 years from the 1 year scan. Cox regression was used to identify 1 year CMR predictors of outcome after adjusting for baseline risk. A total of 262 patients (median age 68 years, 57% males) including 96 at risk for HF, 97 with HF and preserved ejection fraction, and 69 with HF and reduced ejection fraction were included. In the patients with HF, 55 events were identified during follow‐up. After adjustment for baseline clinical risk, Cox proportion hazard regressions only identified 1 year change in left ventricular (LV) mass index as a CMR predictor of outcome, adjusted hazard ratio 1.21 (1.02, 1.44) per 10% increase, P = 0.031. Cardiac remodelling defined as a 1 year change in LV mass index ≥15% was observed in 35% of patients with HF. Patients with adverse remodelling of LV mass index had more events on Kaplan–Meier analyses compared to those with no remodelling, log‐rank P = 0.004 for overall cohort, P = 0.035 for heart failure with preserved ejection fraction and P = 0.035 for heart failure and reduced ejection fraction. Conclusions Cardiac remodelling is common during serial CMR assessment of patients with chronic HF. Change in LV mass predicted long‐term outcomes whereas change in left ventricular ejection fraction did not.

A better understanding of the central role of inflammation in the development of coronary artery disease (CAD) has been the impetus for the evaluation of therapeutic strategies targeting the interleukin-1s/interleukin-6 cytokine signaling pathway, involved in both chronic atherogenesis and in triggering of atherosclerotic plaque rupture. As an inexpensive pharmacologic agent with relatively few adverse effects that tend to be mild and tolerable, the role of colchicine in secondary prevention of atherothrombotic events has been the focus of multiple recent large-scale randomized controlled trials involving patients with stable CAD (Low-Dose Colchicine [LoDoCo] and LoDoCo2 trials), a recent myocardial infarction (Colchicine Cardiovascular Outcome Trial [COLCOT], Colchicine in Patients With Acute Coronary Syndrome [COPS], and Colchicine and Spironolactone in Patients With Myocardial Infarction/Synergy Stent Registry [CLEAR SYNERGY] trials), and undergoing percutaneous coronary interventions (Colchicine in Percutaneous Coronary Intervention [COLCHICINE-PCI] trial). Based on this evidence, low-dose colchicine (0.5 mg once daily) should be considered in patients with recent myocardial infarctions—within 30 days and, ideally, within 3 days—or with stable CAD to improve cardiovascular outcomes. Colchicine should not be used in patients with severe renal or hepatic disease because of the risk of severe toxicity. No serious adverse effect was associated with the combined use of colchicine and high-intensity statin therapy in large trials. The impact of colchicine in high-risk populations of patients with peripheral arterial disease and in those with diabetes for the primary prevention of CAD remains to be established.

Aim Evaluate cerebrovascular autoregulation (CAR) using near-infrared spectroscopy (NIRS) after pediatric cardiac arrest and determine if deviations from CAR-derived optimal mean arterial pressure (MAPopt) are associated with outcomes. Methods CAR was quantified by a moving, linear correlation between time-synchronized mean arterial pressure (MAP) and regional cerebral oxygenation, called cerebral oximetry index (COx). MAPopt was calculated using a multi-window weighted algorithm. We calculated burden (magnitude and duration) of MAP less than 5 mmHg below MAPopt (MAPopt - 5), as the area between MAP and MAPopt - 5 curves using numerical integration and normalized as percentage of monitoring duration. Unfavorable outcome was defined as death or pediatric cerebral performance category (PCPC) at hospital discharge ≥3 with ≥1 change from baseline. Univariate logistic regression tested association between burden of MAP less than MAPopt - 5 and outcome. Results Thirty-four children (median age 2.9 [IQR 1.5,13.4] years) were evaluated. Median COx in the first 24 h post-cardiac arrest was 0.06 [0,0.20]; patients spent 27% [19,43] of monitored time with COx ≥ 0.3. Patients with an unfavorable outcome (n = 24) had a greater difference between MAP and MAPopt - 5 (13 [11,19] vs. 9 [8,10] mmHg, p = 0.01) and spent more time with MAP below MAPopt - 5 (38% [26,61] vs. 24% [14,28], p = 0.03). Patients with unfavorable outcome had a higher burden of MAP less than MAPopt - 5 than patients with favorable outcome in the first 24 h post-arrest (187 [107,316] vs. 62 [43,102] mmHg × Min/Hr; OR 4.93 [95% CI 1.16–51.78]). Conclusions Greater burden of MAP below NIRS-derived MAPopt - 5 during the first 24 h after cardiac arrest was associated with unfavorable outcomes.

Rationale: Animal studies of cardiac arrest suggest that shorter epinephrine dosing intervals than currently recommended (every 3–5 min) may be beneficial in select circumstances. Objectives: To ev...

Objectives Although iron accumulation in pain-processing brain regions has been associated with repeated migraine attacks, brain structural changes associated with post-traumatic headache have yet to be elucidated. To determine whether iron accumulation is associated with acute post-traumatic headache, magnetic resonance transverse relaxation rates (T2*) associated with iron accumulation were investigated between individuals with acute post-traumatic headache attributed to mild traumatic brain injury and healthy controls. Methods Twenty individuals with acute post-traumatic headache and 20 age-matched healthy controls underwent 3T brain magnetic resonance imaging including quantitative T2* maps. T2* differences between individuals with post-traumatic headache versus healthy controls were compared using age-matched paired t-tests. Associations of T2* values with headache frequency and number of mild traumatic brain injuries were investigated using multiple linear regression in individuals with post-traumatic headache. Significance was determined using uncorrected p-value and cluster size threshold. Results Individuals with post-traumatic headache had lower T2* values compared to healthy controls in cortical (bilateral frontal, bilateral anterior and posterior cingulate, right postcentral, bilateral temporal, right supramarginal, right rolandic, left insula, left occipital, right parahippocampal), subcortical (left putamen, bilateral hippocampal) and brainstem regions (pons). Within post-traumatic headache subjects, multiple linear regression showed a negative association between T2* in the right inferior parietal/supramarginal regions and number of mild traumatic brain injuries and a negative association between T2* in bilateral cingulate, bilateral precuneus, bilateral supplementary motor areas, bilateral insula, right middle temporal and right lingual areas and headache frequency. Conclusions Acute post-traumatic headache is associated with iron accumulation in multiple brain regions. Correlations with headache frequency and number of lifetime mild traumatic brain injuries suggest that iron accumulation is part of the pathophysiology or a marker of mild traumatic brain injury and post-traumatic headache.

STUDY DESIGN Retrospective cohort comparison study. OBJECTIVE The aim was to compare perioperative complications and 30-day readmission between ambulatory and inpatient posterior cervical foraminotomy (PCF) in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. SUMMARY OF BACKGROUND DATA Single-level PCF for cervical radiculopathy is increasingly being performed as an ambulatory procedure. Despite this increase, there is a lack of published literature documenting the safety of ambulatory PCF. MATERIALS AND METHODS Patients who underwent PCF (through laminotomy or laminectomy) were identified in the 2005-2018 NSQIP database. Ambulatory procedures were defined as cases that had hospital length of stay=0 days. Inpatient procedures were defined as cases that had length of stay=1-4 days. Patient characteristics, comorbidities, and procedural variables (laminotomy or laminectomy performed) were compared between the 2 cohorts. Propensity score matched comparisons were then performed for postoperative complications and 30-day readmissions between the 2 groups. RESULTS In total, 795 ambulatory and 1789 inpatient single-level PCF cases were identified. After matching, there were 795 ambulatory and 795 inpatient cases. Statistical analysis after propensity score matching revealed no significant difference in individual complications including 30-day readmission, thromboembolic events, wound complications, and reoperation, or aggregated complications between ambulatory versus matched inpatient procedures. Overall 30-day readmissions after ambulatory single-level PCF were noted for 2.46% of the study population, and the most common reasons were surgical site infections (46%) and pain control (15%). CONCLUSIONS The perioperative outcomes assessed in this study support the conclusion that single-level PCF for cervical radiculopathy can be performed for correctly selected patients in the ambulatory setting without increased rates of 30-day perioperative complications or readmissions compared with inpatient procedures. LEVEL OF EVIDENCE Level III.

Despite multiple prior pharmacological trials in traumatic brain injury (TBI), the search for an effective, safe, and practical treatment of these patients remains ongoing. Given the ease of delivery and rapid absorption into the systemic circulation, inhalational gases that have neuroprotective properties will be an invaluable resource in the clinical management of TBI patients. In this review, we perform a systematic review of both pre-clinical and clinical reports describing inhalational gas therapy in the setting of TBI. Hyperbaric oxygen, which has been investigated for many years, and some of the newest developments are reviewed. Also, promising new therapies such as hydrogen gas, hydrogen sulfide gas, and nitric oxide are discussed. Moreover, novel therapies such as xenon and argon gases and delivery methods using microbubbles are explored.

Background Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality worldwide. Data from Canadian populations regarding the burden of ASCVD are limited. Therefore, we describe the 5‐year period prevalence of ASCVD and subsequent major adverse cardiovascular event (MACE) outcomes among patients with ASCVD in Alberta, Canada. Methods A retrospective, observational study was conducted by linking provincial health services data, vital statistics, and pharmaceutical dispenses data. Five‐year period prevalence of clinical ASCVD was captured between 2011 and 2016, and a cohort of adult patients with an initial clinical ASCVD event were identified between 2012 and 2016. One‐year incidence rates (IRs) of subsequent MACE outcomes were calculated as composite and individual measures. A subgroup of patients with acute myocardial infarction (AMI) as their index event was examined. Results There were 198 573 patients (mean [standard deviation] age: 63.9 [15.6] years; 56.6% males) identified with clinical ASCVD between 2012 and 2016. Overall, the 5‐year period prevalence of ASCVD in Alberta was 89.9 per 1000 persons and the 1‐year IR for a primary MACE outcome was 6.15 (95% confidence interval [CI]: 6.03–6.26) per 100 person‐years. Among the ASCVD cohort, 9465 had an AMI as their index event and the IR for a primary MACE outcome was 14.30 (95% CI: 13.45–15.20) per 100 person‐years. Conclusions This study found that the prevalence of ASCVD and the rate of subsequent MACE outcomes 1 year following the initial ASCVD event are substantial, particularly among patients with an AMI. Secondary prevention strategies aimed at lowering this risk are needed for patients with ASCVD.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemiology implicates airborne transmission; aerosol infectiousness and impacts of masks and variants on aerosol shedding are not well understood. Methods We recruited coronavirus disease 2019 (COVID-19) cases to give blood, saliva, mid-turbinate and fomite (phone) swabs, and 30-minute breath samples while vocalizing into a Gesundheit-II, with and without masks at up to 2 visits 2 days apart. We quantified and sequenced viral RNA, cultured virus, and assayed serum samples for anti-spike and anti-receptor binding domain antibodies. Results We enrolled 49 seronegative cases (mean days post onset 3.8 ± 2.1), May 2020 through April 2021. We detected SARS-CoV-2 RNA in 36% of fine (≤5 µm), 26% of coarse (>5 µm) aerosols, and 52% of fomite samples overall and in all samples from 4 alpha variant cases. Masks reduced viral RNA by 48% (95% confidence interval [CI], 3 to 72%) in fine and by 77% (95% CI, 51 to 89%) in coarse aerosols; cloth and surgical masks were not significantly different. The alpha variant was associated with a 43-fold (95% CI, 6.6- to 280-fold) increase in fine aerosol viral RNA, compared with earlier viruses, that remained a significant 18-fold (95% CI, 3.4- to 92-fold) increase adjusting for viral RNA in saliva, swabs, and other potential confounders. Two fine aerosol samples, collected while participants wore masks, were culture-positive. Conclusions SARS-CoV-2 is evolving toward more efficient aerosol generation and loose-fitting masks provide significant but only modest source control. Therefore, until vaccination rates are very high, continued layered controls and tight-fitting masks and respirators will be necessary.

Background Atogepant is an oral, small-molecule, calcitonin gene–related peptide receptor antagonist for the preventive treatment of migraine. Methods In the double-blind, phase 3 ADVANCE trial, participants with 4–14 migraine days/month were randomized to atogepant 10 mg, 30 mg, 60 mg, or placebo once daily for 12 weeks. We evaluated the time course of efficacy of atogepant for the preventive treatment of migraine. Analyses included change from baseline in mean monthly migraine days during each of the three 4-week treatment periods, change in weekly migraine days during weeks 1–4, and proportion of participants with a migraine on each day during the first week. Results We analyzed 873 participants (n = 214 atogepant 10 mg, n = 223 atogepant 30 mg, n = 222 atogepant 60 mg, n = 214 placebo). For weeks 1–4, mean change from baseline in mean monthly migraine days ranged from −3.1 to −3.9 across atogepant doses vs −1.6 for placebo ( p Conclusion Atogepant demonstrated treatment benefits as early as the first full day after treatment initiation, and sustained efficacy across each 4-week interval during the 12-week treatment period. Clinical trial registration: ClinicalTrials.gov identifier: NCT03777059

Background: Computed tomography (CT) and magnetic resonance imaging (MRI) studies are used separately for surgical planning of spine surgery. Advanced techniques exist for creating CT-MR fusion images, but at this time these techniques are not easily accessible for large-scale use. Technique: We propose a simple graphical technique for CT-MR image overlay, for use in the surgical planning of spinal decompression and guidance of intraoperative resection. The proposed technique involves overlaying a single cross-section from anatomically comparable MRI and CT studies on any software with basic image editing functions. Results: We demonstrate CT-MR fusion images of 8 patients of the senior author in which the technique was used. We found that it can also be referenced intraoperatively for navigation.Conclusions: Compared to other techniques, our proposed method can be easily implemented by clinicians to create simple CT-MRI fusion images that can be useful for preoperative planning and intraoperative navigation.

INTRODUCTION: This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of central disorders of hypersomnolence in adults and children. The review focuses on prescription medications with U.S. Food & Drug Administration approval and nonpharmacologic interventions studied for the treatment of symptoms caused by central disorders of hypersomnolence. METHODS: The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine to perform a systematic review. Randomized controlled trials and observational studies addressing pharmacological and nonpharmacological interventions for central disorders of hypersomnolence were identified. Statistical analyses were performed to determine the clinical significance of all outcomes. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was used to assess the evidence for the purpose of making specific treatment recommendations. RESULTS: The literature search identified 678 studies; 144 met the inclusion criteria and 108 provided data suitable for statistical analyses. Evidence for the following interventions is presented: armodafinil, clarithromycin, clomipramine, dextroamphetamine, flumazenil, intravenous immune globulin (IVIG), light therapy, lithium, l-carnitine, liraglutide, methylphenidate, methylprednisolone, modafinil, naps, pitolisant, selegiline, sodium oxybate, solriamfetol, and triazolam. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. CITATION: Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2021;17(9):1895–1945.

Due to their reduced frequency of dosing and ease of availability, NSAIDs are generally preferred over opioids for rodent analgesia. We evaluated the efficacy of the highly COX2-selective NSAID firocoxib as compared with meloxicam and buprenorphine for reducing allodynia and hyperalgesia in rats in a plantar incision model of surgical pain. After a preliminary pharmacokinetic study using firocoxib, Sprague–Dawley rats (n = 12 per group, 6 of each sex) were divided into 6 groups: no surgery (anesthesia only), saline (surgery but no analgesia), buprenorphine (0.05 mg/kg SC every 8 h), meloxicam (2 mg/kg SC every 24 h), and 2 dosages of firocoxib (10 and 20 mg/kg SC every 24 h). The nociception assays were performed by using von Frey and Hargreaves methodology to test mechanical allodynia and thermal hyperalgesia. These assays were performed at 24 h before and at 20, 28, 44, and 52 h after start of surgery. None of the analgesics used in this study produced significantly different responses in allodynia or hyperalgesia from those of saline-treated rats. In the Hargreaves assay, female saline-treated rats experienced significantly greater hyperalgesia than did males. These findings add to a growing body of literature suggesting that commonly used dosages of analgesics may not provide sufficient analgesia in rats experiencing incisional pain.

OBJECTIVE Single-ventricle congenital heart disease (CHD) in pediatric patients with Glenn and Fontan physiology represents a unique physiology requiring the surgical diversion of the systemic venous return from the superior vena cava (Glenn) and then the inferior vena cava (Fontan) directly to the pulmonary arteries. Because many of these patients are on chronic anticoagulation therapy and may have right-to-left shunts, arrhythmias, or lymphatic disorders that predispose them to bleeding and/or clotting, they are at risk of experiencing neurological injury requiring intubation and positive pressure ventilation, which can significantly hamper pulmonary blood flow and cardiac output. The aim of this study was to describe the complex neurological and cardiopulmonary interactions of these pediatric patients after acute central nervous system (CNS) injury. METHODS The authors retrospectively analyzed the records of pediatric patients who had been admitted to a quaternary children’s hospital with CHD palliated to bidirectional Glenn (BDG) or Fontan circulation and acute CNS injury and who had undergone intubation and mechanical ventilation. Patients who had been admitted from 2005 to 2019 were included in the study. Clinical characteristics, surgical outcomes, cardiovascular and pulmonary data, and intracranial pressure data were collected and analyzed. RESULTS Nine pediatric single-ventricle patients met the study inclusion criteria. All had undergone the BDG procedure, and the majority (78%) were status post Fontan palliation. The mean age was 7.4 years (range 1.3–17.3 years). At the time of acute CNS injury, which included traumatic brain injury, intracranial hemorrhage, and cerebral infarct, the median time interval from the most recent cardiac surgical procedure was 3 years (range 2 weeks–11 years). Maintaining normocarbia to mild hypercarbia for most patients during intubation periods did not cause neurological deterioration, and hemodynamic profiles were more favorable as compared to periods of hypocarbia. Hypocarbia was associated with unfavorable hemodynamics but was necessary to decrease intracranial hypertension. Most patients were managed using low mean airway pressure (MAWP) in order to minimize the impact on preload and cardiac output. CONCLUSIONS The authors highlight the complex neurological and cardiopulmonary interactions with respect to partial pressure of arterial CO2 (PaCO2) and MAWP when pediatric CHD patients with single-ventricle physiology require mechanical ventilation. The study data demonstrated that tight control of PaCO2 and minimizing MAWP with the goal of early extubation may be beneficial in this population. A multidisciplinary team of pediatric critical care intensivists, cardiac intensivists and anesthesiologists, and pediatric neurosurgeons and neurologists are recommended to ensure the best possible outcomes.

Background: Rapid diagnostic tests (RDTs) for bacteremia allow for early antimicrobial therapy modification based on organism and resistance gene identification. Studies suggest patient outcomes are optimized when infectious disease (ID)-trained antimicrobial stewardship personnel intervene on RDT results. However, data are limited regarding RDT implementation at small community hospitals, which often lack access to on-site ID clinicians. Methods: This study evaluated the impact of RDTs with and without real-time pharmacist intervention (RTPI) at a small community hospital with local pharmacist training and asynchronous support from a remote ID Telehealth pharmacist. Time to targeted therapy (TTT) in patients with bacteremia was compared retrospectively across 3 different time periods: a control without RDT, RDT-only, and RDT with RTPI. Results: Median TTT was significantly faster in both the RDT with RTPI and RDT-only groups compared with the control group (2 vs 25 vs 51 hours respectively; P

Background: Cannabidiol (CBD) is a cannabis derivative that has been popularized as a medicinal product with analgesic and anti-inflammatory effects. Given the anecdotal observations that several patients have reported use of CBD for spine-related pain, this study was designed to characterize CBD consumption patterns and perceived effects in patients with spine-related complaints. Methods: The study design was a cross-sectional survey. Over a 4-week period, an anonymous paper survey was administered to all patients presenting for evaluation by 1 of 9 spine surgeons at a single institution. Surveys were given upon registration for the office visit and collected by the office manager or nurse before evaluation by the surgeon. Patients were included regardless of surgical status (ie, preoperative, postoperative, or nonoperative) or region of pathology (lumbar, thoracic, or cervical). The survey consisted of multiple-choice questions on patient patterns of CBD use. Results: Out of 300 surveys, 214 (71%) were completed. CBD use for spine-related pain was reported by 54 (25.2%) patients. CBD was initially used for potential relief of back pain (66.7%), neck pain (37.0%), leg pain (35.2%), and/or arm pain (9.3%). Users also sought improvements in insomnia (25.9%) and mood (18.5%). Oil was the most popular formulation (64.8%). CBD was most often consumed 2–5 times (40.7%) or 6–10 times (31.5%) per week. The most common source of initial recommendation for CBD was friends or family (75.9%). Reported benefits were pain relief (46.3%), improved sleep (33.3%), and reduced anxiety (20.4%); however, 24.1% of patients reported no benefit from CBD use. The most reported side effect was fatigue (7.4%). Most users (63.0%) would recommend CBD to a friend for pain relief. Conclusion: CBD is already used by many patients, and further high-quality research on this supplement is essential. Level of Evidence: 4. Clinical Relevance: CBD is a commonly used by spine patients as an off label treatment.

Passion is a motivational force driving people toward success and satisfaction. Outside of entrepreneurship, though, research on how passion may be activated within a work role has been limited. As frontline employees (FLEs) are a vital link between organizations and their customers, measuring passion in the FLE context is particularly relevant. Anyone who has enjoyed memorable service knows, it is through passionate FLEs that service organizations may stand out from competitors. Through a series of seven studies conducted across multiple countries, this research develops and validates a measure of FLE passion. FLE passion is the intense positive feelings and identity reinforcement resulting from solving problems and/or serving customers. The developed and validated measurement instrument is comprised of both serving and solving dimensions and includes evidence that FLEs negotiate their identities and activate positive affect during service encounters. Theory and results indicate that organizations may control certain antecedents to passion, and that passion is related, yet distinct, from such things as employee engagement and organizational commitment. A potential research agenda is presented based upon applying the FLE passion construct across various service domains.

Purpose This study aims to test the role of a firm’s marketing and technological capabilities in mediating the relationship between customer involvement in information provision (CIP) and customer involvement in coproduction (CIC) and new product performance, while also investigating the impact of the interactive effect of such capabilities. This investigation is at the firm rather than the project level. Design/methodology/approach A survey-based questionnaire was distributed to senior managers from 101 Taiwanese electronics firms. The research model and hypotheses were evaluated using partial least squares structural equation modeling in SmartPLS 3. Findings CIP and CIC improve new product performance indirectly through the development of marketing and technological capabilities. CIP has a stronger positive effect on marketing capabilities than CIC. In addition, the interactive effect of marketing and technological capabilities on new product performance is positive and significant. Research limitations/implications The data came from a single respondent in each firm, which may lead to common method bias. In addition, the data were cross-sectional in nature, having been collected at a single point in time. This limits the ability to draw causal inferences, as would be possible with longitudinal data. Finally, the data came from a single industry in only one country. Practical implications CIC is useful in terms of product idea generation and screening, as well as in helping to effectively learn and combine market knowledge from customers, whereas CIP takes on a more active role in strengthening marketing capabilities. Managers should understand these direct effects of CIP and CIC, as well as their indirect effects on new product performance. Originality/value Previous empirical research is largely limited to project-level implications such as innovativeness, advantages and the financial performance of a specific new product; a clear understanding of the strategic, firm-level implications of CIP and CIC in the context of new product development is lacking. The findings highlight the importance of treating CIP and CIC as continuous processes in a firm rather than viewing each in isolation to a specific project.

OBJECTIVE Our objective is to characterize the incidence of tracheostomy placement and of new requirement for long-term mechanical ventilation after extracorporeal membrane oxygenation (ECMO) among children with acute respiratory failure. We examine whether an association exists between demographics, pre-ECMO and ECMO clinical factors, and the placement of a tracheostomy or need for long-term mechanical ventilation. METHODS A retrospective multicenter cohort study was conducted at 10 quaternary care pediatric academic centers, including children supported with veno-venous (V-V) ECMO from 2011 to 2016. RESULTS Among 202 patients, 136 (67%) survived to ICU discharge. All tracheostomies were placed after ECMO decannulation, in 22 patients, with 19 of those surviving to ICU discharge (14% of survivors). Twelve patients (9% of survivors) were discharged on long-term mechanical ventilation. Tracheostomy placement and discharge on home ventilation were not associated with pre-ECMO severity of illness or pre-existing chronic illness. Patients who received a tracheostomy were older and weighed more than patients who did not receive a tracheostomy, although this association did not exist among patients discharged on home ventilation. ECMO duration was longer in those who received a tracheostomy compared with those who did not, as well as for those discharged on home ventilation, compared to those who were not. CONCLUSION The 14% rate for tracheostomy placement and 9% rate for discharge on long-term mechanical ventilation after V-V ECMO are important patient-centered findings. This study informs anticipatory guidance provided to families of patients requiring prolonged respiratory ECMO support, and lays the foundation for future research.

Background Headache is one of the most common symptoms after concussion, and mild traumatic brain injury (mTBI) is a risk factor for chronic migraine (CM). However, there remains a paucity of data regarding the impact of mTBI on migraine-related symptoms and clinical course. Methods Of 2161 migraine patients who participated in the American Registry for Migraine Research between February 2016 and March 2020, 1098 completed questions assessing history of TBI (50.8%). Forty-four patients reported a history of moderate to severe TBI, 413 patients reported a history of mTBI. Patients’ demographics, headache symptoms and triggers, history of physical abuse, allodynia symptoms (ASC-12), migraine disability (MIDAS), depression (PHQ-2), and anxiety (GAD-7) were compared between migraine groups with (n = 413) and without (n = 641) a history of mTBI. Either the chi-square-test or Fisher’s exact test, as appropriate, was used for the analyses of categorical variables. The Mann-Whitney test was used for the analyses of continuous variables. Logistic regression models were used to compare variables of interest while adjusting for age, gender, and CM. Results A significantly higher proportion of patients with mTBI had CM (74.3% [307/413] vs. 65.8% [422/641], P = 0.004), had never been married or were divorced (36.6% [147/402] vs. 29.4% [187/636], P = 0.007), self-reported a history of physical abuse (24.3% [84/345] vs. 14.3% [70/491], P P = 0.003), had headache-related vertigo (23.0% [95/413] vs. 15.9% [102/640], P = 0.009), and difficulty finding words (43.0% [174/405] vs. 32.9% [208/633], P P = 0.018) and reading (6.6% [26/393] vs. 3.0% [18/607], P = 0.016), compared to patients without mTBI. Patients with mTBI had significantly greater ASC-12 scores (median [interquartile range]; 5 [1–9] vs. 4 [1–7], P P = 0.034), and PHQ-2 scores (1 [0–2] vs. 1 [0–2], P = 0.012). Conclusion Patients with a history of mTBI are more likely to have a self-reported a history of physical abuse, vertigo, and allodynia during headache attacks, headaches triggered by lack of sleep and reading, greater headache burden and headache disability, and symptoms of anxiety and depression. This study suggests that a history of mTBI is associated with the phenotype, burden, clinical course, and associated comorbid diseases in patients with migraine, and highlights the importance of inquiring about a lifetime history of mTBI in patients being evaluated for migraine.

In patients with acute coronary syndromes (ACS), guidelines recommend the assessment of left-ventricular ejection fraction (LVEF). Many patients with ACS undergo multiple assessments of LVEF, the clinical value of which is unknown.Patients with ACS undergoing cardiac catheterization between 2012 and 2016 were evaluated and assessments of LV function identified. To evaluate changes in LVEF over time, available echocardiograms were reviewed in a subsample of patients with LVEF data available (n = 3221). Patients with ACS were classified into 3 groups: group 1 (LVEF50%), group 2 (LVEF 35% to 50%), and group 3 (LVEF35%).Our cohort consisted of 8327 patients with ACS (76% men), presenting with a mean age of 62.4 ± 12.4 years. At index presentation, 66% of patients had an LVEF50%, 27% had an LVEF between 35% and 50%, and 7% had severely reduced LVEF of35%. More than half of the cohort (n = 4600) had follow-up assessment of LV function, performed over an average of 2.71 ± 1.31 years. In the subsample of 3221 patients, only 1.1% of those in group 1, and 5.1% of those in group 2, deteriorated to an LVEF35%.Patients with ACS often undergo multiple assessments of LV function. Those with initially preserved EF rarely demonstrate a decline in EF to35%. A reduction in low-value cardiac tests may be an important first step in improving the quality of care for patients with ACS.En cas de syndrome coronarien aigu (SCA), les lignes directrices recommandent d’évaluer la fraction d’éjection ventriculaire gauche (FEVG). Beaucoup de patients présentant un SCA subissent plusieurs évaluations de la FEVG, une pratique dont on ne connaît pas la valeur clinique.Nous avons examiné les dossiers de patients atteints d’un SCA ayant subi un cathétérisme cardiaque entre 2012 et 2016 afin de relever les évaluations de la fonction ventriculaire gauche. Pour évaluer l’évolution de la FEVG au fil du temps, nous avons examiné les échocardiogrammes d’un sous-échantillon de patients pour lesquels des données sur la FEVG étaient disponibles (n = 3 221). Les patients présentant un SCA ont été divisés en trois groupes : groupe 1 (FEVG50 %), groupe 2 (FEVG de 35 à 50 %) et groupe 3 (FEVG35 %).Notre cohorte comprenait 8 327 patients présentant un SCA (proportion d’hommes : 76 %), dont l’âge moyen était de 62,4 ± 12,4 ans. Au moment de la manifestation de référence, 66 % des patients avaient une FEVG50 %, 27 %, une FEVG de 35 à 50 % et 7 %, une FEVG gravement réduite35 %. Plus de la moitié des patients de la cohorte (n = 4 600) ont subi une évaluation de suivi de la fonction ventriculaire gauche, effectuée sur une période de 2,71 ± 1,31 ans en moyenne. Dans le sous-échantillon de 3 221 patients, seulement 1,1 % des patients du groupe 1 et 5,1 % de ceux du groupe 2 ont vu leur FEVG se détériorer à une valeur35 %.Les patients présentant un SCA subissent souvent plusieurs évaluations de la fonction ventriculaire gauche. Ceux dont la fraction d’éjection était initialement préservée ont rarement présenté une réduction de la fraction d’éjection en deçà de 35 %. Une réduction du nombre d’évaluations cardiaques offrant peu de valeur pourrait constituer un premier pas important vers l’amélioration de la qualité des soins prodigués aux patients présentant un SCA.

Summary Background & aims Consumption of rapid digesting sugars by children are under increased scrutiny because of their contribution to unhealthy weight gain. Previous studies in adults and children have suggested that altering the blend of carbohydrates (CHOs) consumed may cause shifts in substrate utilization. The purpose of this study was to examine the effects of consuming a slow digesting carbohydrate (SDC) and rapid digesting carbohydrate (RDC) on CHO and fat oxidation, glucose, and insulin responses at rest, during exercise, and post-exercise rest in pre-pubescent children. Methods A randomized, double-blind, crossover design was used. Nineteen pre-pubescent children (n = 10 boys, n = 9 girls, mean ± standard error, age = 9.84 ± 0.37-yrs) participated. Visits to the laboratory began with a 30-min measurement of resting metabolism followed by consumption of either an RDC or SDC drink. Postprandial resting metabolism was recorded for 60-min, immediately followed by 60-min of submaximal cycling exercise while metabolism was recorded, which was immediately followed by another 60-min recording of post-exercise metabolism. Total CHO and fat oxidation, endogenous and exogenous CHO oxidation, blood glucose, and insulin were assessed. Results Total CHO oxidation rate (g∙min−1) was greater after the RDC drink at 60 min (p = 0.032). Endogenous CHO oxidation rate (g∙min−1) was greater after the SDC drink at 15 min (p ≤ 0.010). Cumulative endogenous CHO oxidation (g) was greater after the SDC drink at 45 min (p = 0.009). Endogenous CHO oxidation accounted for a greater proportion of substrate oxidation after the first 60-min rest period (p = 0.028), while exogenous CHO oxidation accounted for a greater proportion of substrate oxidation for the RDC at all time points (p ≤ 0.019). Conclusions The present study provides novel data suggesting that an SDC promotes greater endogenous substrate utilization in pre-pubertal children, which may have beneficial health impacts on energy intake and carbohydrate regulation/metabolism during growth and development. Clinical trials registry number NCT03185884, clinicaltrials.gov

Patient–ventilator asynchrony (PVA) is commonly encountered during mechanical ventilation of critically ill patients. Estimates of PVA incidence vary widely. Type, risk factors, and consequences of PVA remain unclear. We aimed to measure the incidence and identify types of PVA, characterize risk factors for development, and explore the relationship between PVA and outcome among critically ill, mechanically ventilated adult patients admitted to medical, surgical, and medical-surgical intensive care units in a large academic institution staffed with varying provider training background. A single center, retrospective cohort study of all adult critically ill patients undergoing invasive mechanical ventilation for ≥ 12 h. A total of 676 patients who underwent 696 episodes of mechanical ventilation were included. Overall PVA occurred in 170 (24%) episodes. Double triggering 92(13%) was most common, followed by flow starvation 73(10%). A history of smoking, and pneumonia, sepsis, or ARDS were risk factors for overall PVA and double triggering (all P P P

Objective “Pain interference” and “headache impact” refer to negative consequences that pain and headache have on one’s life. This study investigated determinants of these negative impacts in a large patient cohort who have chronic migraine with medication overuse. Methods Six hundred and eleven adults were enrolled from 34 headache, neurology, and primary care clinics. Negative consequences of chronic migraine with medication overuse were determined using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference 6b questionnaire and the Headache Impact Test 6. Relationships between PROMIS-6b and Headache Impact Test 6 scores with demographics, headache characteristics, medication use, anxiety symptoms, and depression symptoms were assessed with linear regression. Elastic Net regression was used to develop a multiple regression model. Results PROMIS-6b T-Scores averaged 65.2 (SD 5.4) and Headache Impact Test 6 scores averaged 65.0 (SD 5.3), indicating severe negative consequences of chronic migraine with medication overuse. Chronic migraine with medication overuse interfered with enjoyment of life, concentration, daily activities, doing tasks away from home, and socializing. Depression symptom severity had the strongest relationship with pain interference and headache impact. Moderate-to-severe headache frequency, headache intensity, and anxiety symptoms were also associated with pain interference and headache impact. Conclusions Chronic migraine with medication overuse is associated with substantial negative consequences, the extent of which is most strongly related to depression symptoms.

Aim Inhaled nitric oxide (iNO) during cardiopulmonary resuscitation (CPR) improved systemic hemodynamics and outcomes in a preclinical model of adult in-hospital cardiac arrest (IHCA) and may also have a neuroprotective role following cardiac arrest. The primary objectives of this study were to determine if iNO during CPR would improve cerebral hemodynamics and mitochondrial function in a pediatric model of lipopolysaccharide-induced shock-associated IHCA. Methods After lipopolysaccharide infusion and ventricular fibrillation induction, 20 1-month-old piglets received hemodynamic-directed CPR and were randomized to blinded treatment with or without iNO (80 ppm) during and after CPR. Defibrillation attempts began at 10 min with a 20-min maximum CPR duration. Cerebral tissue from animals surviving 1-h post-arrest underwent high-resolution respirometry to evaluate the mitochondrial electron transport system and immunohistochemical analyses to assess neuropathology. Results During CPR, the iNO group had higher mean aortic pressure (41.6 ± 2.0 vs. 36.0 ± 1.4 mmHg; p = 0.005); diastolic BP (32.4 ± 2.4 vs. 27.1 ± 1.7 mmHg; p = 0.03); cerebral perfusion pressure (25.0 ± 2.6 vs. 19.1 ± 1.8 mmHg; p = 0.02); and cerebral blood flow relative to baseline (rCBF: 243.2 ± 54.1 vs. 115.5 ± 37.2%; p = 0.02). Among the 8/10 survivors in each group, the iNO group had higher mitochondrial Complex I oxidative phosphorylation in the cerebral cortex (3.60 [3.56, 3.99] vs. 3.23 [2.44, 3.46] pmol O2/s mg; p = 0.01) and hippocampus (4.79 [4.35, 5.18] vs. 3.17 [2.75, 4.58] pmol O2/s mg; p = 0.02). There were no other differences in mitochondrial respiration or brain injury between groups. Conclusions Treatment with iNO during CPR resulted in superior systemic hemodynamics, rCBF, and cerebral mitochondrial Complex I respiration in this pediatric cardiac arrest model.

There are data underlining the relationship between muscle health and spine related pathology, but little data regarding changes in paralumbar muscle associated with lumbar spondylolisthesis. We aimed to define changes in paralumbar muscle health associated with spondylolisthesis. A retrospective review was performed on consecutive patients with lumbar spine pathology requiring an operation. A pre-operative lumbar MRI was analysed for muscle health measurements including lumbar indentation value (LIV), paralumbar cross-sectional area divided by body mass index (PL-CSA/BMI), and Goutallier classification of fatty atrophy. All measurements were taken from an axial slice of a T2-weighted image at lumbar disc spaces. Baseline health-related quality of life scores (HRQOLs), narcotic use and areas of stenosis were tracked. We performed Chi-square analyses and student’s t test to determine statistically significant differences between cohorts. There were 307 patients (average age 56.1 ± 16.7 years, 141 females) included within our analysis. 112 patients had spondylolisthesis. There were no differences in baseline HRQOLs between the spondylolisthesis cohort (SC) and non-spondylolisthesis cohort (non-SC). There were significantly worse PL-CSA/BMI at L2-L3 (p = 0.03), L3-L4 (p = 0.04) and L4-L5 (p = 0.02) for the SC. Goutallier classification of paralumbar muscle was worse for SC at L1-L2 (p = 0.04) and at L4-L5 (p

Study design This is a prospective observational study. Objective The aim was to record daily opioid use and pain levels after 1-level or 2-level anterior cervical discectomy and fusion (ACDF) or cervical disc arthroplasty (CDA). Summary of background data Data to inform opioid prescription guidelines following ACDF or CDA is lacking. Understanding postoperative opioid consumption behaviors is critical to provide appropriate postdischarge prescriptions. Methods Patients undergoing 1-level or 2-level primary ACDF or CDA were consecutively enrolled at 2 participating institutions between March 2018 and March 2019. Patients with opioid dependence (defined as daily use ≥6 mo before surgery) were excluded. Starting postoperative day 1, daily opioid use and numeric pain rating scale pain levels were collected through a Health Insurance Portability and Accountability Act-compliant, automated text-messaging system. To facilitate clinical applications, opioid use was converted from oral morphine equivalents into "pills" (oxycodone 5 mg equivalents). After 6 weeks or upon patient-reported cessation of opioid use, final survey questions were asked. Refill data were verified from the state prescription registry. Risk factors for patients in top quartile of consumption were analyzed. Results Of 57 patients, 48 completed the daily queries (84.2%). Mean age of the patient sample was 50.2±10.9 years. Thirty-two patients (66.7%) underwent ACDF and 16 CDA (33.3%); 64.6% one level; 35.4% two levels. Median postdischarge use was 6.7 pills (range: 0-160). Cumulative opioid use did not vary between the 1-level and 2-level groups (median pill consumption, 10 interquartile range: 1.3-31.3 vs. 4 interquartile range: 0-18, respectively, P=0.085). Thirteen patients (27.1%) did not use any opioids after discharge. Of those patients that took opioids after discharge, half ceased opioids by postoperative day 8. Preoperative intermittent opioid use was associated with the top quartile of opioid consumption (9.1% vs. 50%, P=0.006). Conclusion Given that most patients use few opioids, patients could be offered the option of a 12 oxycodone 5 mg (90 oral morphine equivalents) discharge prescription, accompanied by education on appropriate opioid use and disposal.

BACKGROUND: Current mechanical ventilation practice and the use of treatment adjuncts in patients requiring extracorporeal membrane oxygenation (ECMO) for refractory hypoxemia (RH) vary widely and their impact on outcomes remains unclear. In 2015, we implemented a standardized approach to protocolized ventilator settings and guide the escalation of adjunct therapies in patients with RH. This study aimed to investigate ICU mortality, its associated risk factors, and mechanical ventilation practice before and after the implementation of a standardized RH guideline in patients requiring venovenous ECMO (VV-ECMO). METHODS: This was a single-center, retrospective cohort study of patients undergoing VV-ECMO due to RH respiratory failure between January 2008 and March 2015 (before RH protocol implementation) and between April 2015 and October 2019 (after RH protocol implementation). RESULTS: A total of 103 subjects receiving VV-ECMO for RH were analyzed. After implementation of the RH protocol, more subjects received prone positioning (6.7% vs 23.3%, P = .02), and fewer received high-frequency oscillatory ventilation than before launching the RH protocol (0% vs 13.3%, P = .01). Plateau pressure was also lower before initiation of ECMO (P = .04) and at day 1 during ECMO (P = .045). Driving pressure was consistently lower at days 1, 2, and 3 after ECMO initiation: median 13.0 (interquartile range [IQR] 10.6–18.0) vs 16.0 (IQR 14.0–20.0) cm H2O at day 1 (P = .003); 13.0 (IQR 11.0–15.9) vs 15.5 (IQR 12.0–20.0) cm H2O at day 2 (P = .03); and 12.0 (IQR 10.0–14.5) vs 15.0 (IQR 12.0–19.0) cm H2O at day 3 (P = .005). CONCLUSIONS: The implementation of a standardized RH guideline improved compliance with a lung-protective ventilation strategy and utilization of the prone position and was associated with lower driving pressure during the first 3 days after ECMO initiation in subjects with refractory hypoxemia.

Background Galcanezumab is a monoclonal antibody (mAb) that binds calcitonin gene-related peptide (CGRP) and is indicated for the preventive treatment of migraine. Galcanezumab demonstrated early onset of effect in patients with migraine but it is unknown whether the same holds true for patients who have not benefited from multiple prior migraine preventives. Methods Patients with episodic or chronic migraine from a 3-month, randomized, double-blind, placebo-controlled, phase 3b study (CONQUER) who had 2 to 4 migraine preventive medication category failures in the past 10 years were randomized 1:1 to placebo (N = 230) or galcanezumab 120 mg/month (240 mg loading dose; N = 232). In this post-hoc analysis, change from baseline in number of monthly and weekly migraine headache days was assessed. Monthly onset of effect was the earliest month at which significant improvement with galcanezumab compared to placebo was achieved and maintained at all subsequent months. Weekly onset was the initial week at which statistical separation was achieved and maintained at all subsequent weeks during that month. Proportion of patients with migraine headache days in the first week of treatment, and patients achieving ≥50%, ≥75%, and 100% response by month and week were also assessed. Results Galcanezumab-treated patients had a significantly greater reduction in monthly migraine headache days starting at month 1, which remained significant for all subsequent months compared to placebo (all p ≤ 0.0001, month 1 mean change from baseline: placebo − 0.7; galcanezumab − 4.0). Weekly migraine headache days was significantly reduced in galcanezumab-treated patients starting at week 1 and continued for each subsequent week of month 1 compared to placebo (all p p p p Conclusion Galcanezumab showed early onset of effect beginning the day after treatment initiation in patients who had not previously benefited from migraine preventive treatments. Trial registration ClinicalTrials.gov, NCT03559257. Registered 18 June 2018.

Study design This was a retrospective review. Objective The objective of this study was to describe our technique and evaluate the time demand, radiation exposure, and outcomes of minimally invasive posterior cervical laminoforaminotomy (MI-PCLF) using skin-anchored intraoperative navigation (ION). Background Although bone-anchored trackers are most commonly used for ION, a novel technique utilizing noninvasive skin-anchored trackers has recently been described for lumbar surgery and has shown favorable results. There are currently no reports on the use of this technology for cervical surgery. Methods Time demand, radiation exposure, and perioperative outcomes of MI-PCLF using skin-anchored ION were evaluated. Results Twenty-one patients with 36 operative levels were included. Time for ION setup and operative time were a median of 34 and 62 minutes, respectively. Median radiation to the patient was 2.5 mGy from 10 seconds of fluoroscopy time. Radiation exposure to operating room personnel was negligible because they are behind a protective lead shield during ION image acquisition. There were no intraoperative complications or wrong-level surgeries. One patient required a repeat ION spin, and in 2 patients, ION was abandoned and standard fluoroscopy was used. Conclusions Skin-anchored ION for MI-PCLF is feasible, safe, and accurate. It results in short operative times, minimal complications, low radiation to the patient, and negligible radiation to operating room personnel.

Neurologic injury is a leading cause of morbidity and mortality following pediatric cardiac arrest. In this study, we assess the feasibility of quantitative, non-invasive, frequency-domain diffuse optical spectroscopy (FD-DOS) neuromonitoring during cardiopulmonary resuscitation (CPR), and its predictive utility for return of spontaneous circulation (ROSC) in an established pediatric swine model of cardiac arrest. Cerebral tissue optical properties, oxy- and deoxy-hemoglobin concentration ([HbO2], [Hb]), oxygen saturation (StO2) and total hemoglobin concentration (THC) were measured by a FD-DOS probe placed on the forehead in 1-month-old swine (8–11 kg; n = 52) during seven minutes of asphyxiation followed by twenty minutes of CPR. ROSC prediction and time-dependent performance of prediction throughout early CPR (w, w = 0.1) with tenfold cross-validation. FD-DOS CPR data was successfully acquired in 48/52 animals; 37/48 achieved ROSC. Changes in scattering coefficient (785 nm), [HbO2], StO2 and THC from baseline were significantly different in ROSC versus No-ROSC subjects (p 2] of + 1.3 µmol/L from 1-min of CPR achieved the highest weighted Youden index (0.96) for ROSC prediction. We demonstrate feasibility of quantitative, non-invasive FD-DOS neuromonitoring, and stable, specific, early ROSC prediction from the third minute of CPR.

With advances in synthetic biology and genome engineering comes a heightened awareness of potential misuse related to biosafety concerns. A recent study employed machine learning to identify the lab-of-origin of DNA sequences to help mitigate some of these concerns. Despite their promising results, this deep learning based approach had limited accuracy, was computationally expensive to train, and wasn’t able to provide the precise features that were used in its predictions. To address these shortcomings, we developed PlasmidHawk for lab-of-origin prediction. Compared to a machine learning approach, PlasmidHawk has higher prediction accuracy; PlasmidHawk can successfully predict unknown sequences’ depositing labs 76% of the time and 85% of the time the correct lab is in the top 10 candidates. In addition, PlasmidHawk can precisely single out the signature sub-sequences that are responsible for the lab-of-origin detection. In summary, PlasmidHawk represents an explainable and accurate tool for lab-of-origin prediction of synthetic plasmid sequences. PlasmidHawk is available at https://gitlab.com/treangenlab/plasmidhawk.git., Advances in synthetic biology and genome engineering raise awareness of potential misuse. Here, the authors present PlasmidHawk, a sequence alignment based method for lab-of-origin prediction.

Over the past decade, artificial intelligence has been propelled forward by advances in machine learning algorithms and computational hardware, opening up myriads of new avenues for scientific research. Nevertheless, virtual assistants and voice control have yet to be widely used in the natural sciences. Here, we present ChemVox, an interactive Amazon Alexa skill that uses speech recognition to perform quantum chemistry calculations. This new application interfaces Alexa with cloud computing and returns the results through a capable device. ChemVox paves the way to making computational chemistry routinely accessible to the wider community. Using voice-based technologies, ChemVox is able to answer quantum chemistry questions in seconds, thus making such complex questions more accessible to the community.

Objective Persistent posttraumatic headache (PPTH), one of the most common symptoms following mild traumatic brain injury, is often associated with substantial functional disability. The objective of this study was to assess the contribution of demographics, headache characteristics, and psychological symptoms to disability associated with PPTH. Methods Participants completed the State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory (BDI), the Pain Catastrophizing Scale (PCS), and the Migraine Disability Assessment (MIDAS) questionnaire. Two linear regression models were formulated to interrogate the relationships between 1) demographics and headache characteristics with the MIDAS questionnaire and 2) demographics, headache characteristics, and psychological symptoms with the MIDAS questionnaire. A two-way stepwise regression using the Akaike information criterion was performed to find a parsimonious model describing the relationships between demographics, headache characteristics, and psychological measures with the MIDAS questionnaire. Results Participants included 58 patients with PPTH and 39 healthy controls (HCs). The median MIDAS score among those with PPTH was 48.0 (first quartile [1Q] = 20.0, third quartile [3Q] = 92.0), indicative of severe disability. Compared with the HCs, those with PPTH had higher scores on the BDI, STAI, and PCS. Older age predicted lower MIDAS scores (age: B=–0.11, P Conclusions Individuals with PPTH had substantial psychological symptoms and headache-related disability. Disability was partially explained by age, headache frequency and intensity, and trait anxiety. Holistic management of patients with PPTH to address headaches and psychological symptoms might reduce headache-associated disability.

Localized tissue bioimpedance is being widely investigated as a technique to identify physiological features in support of health focused applications. In support of this method being translated into wearable systems for continuous monitoring, it is critical to not only collect measurements but also evaluate their quality. This is necessary to reduce errors in equipment or measurement conditions from contributing data artifacts to datasets that will be analyzed. Two methods for artifact identification in resistance measurements of bioimpedance datasets are presented. These methods, based on thresholding and trend detection, are applied to localized knee bioimpedance datasets collected from two knee sites over 7 consecutive days in free-living conditions. Threshold artifacts were identified in 0.04% (longitudinal and transverse) and 0.69% (longitudinal)/3.50% (transverse) of the total data collected.

Retail managers are critical to the effective performance of a firm given their key role of implementing retailer strategy through the behaviors and attitudes that are instilled within frontline employees. Yet, empirical work in retailing rarely attempts to incorporate perspectives of both the store manager and frontline employee, as well as integrating customer-focused outcomes. In this study, based upon predictions of social exchange theory, we present empirical results that provide an integrative view of how leader-member exchange quality influences the development of a frontline employee’s brand relationship, which ultimately influences retail employee performance and customer loyalty/brand equity. The strength of the observed empirical relationships is influenced by contextual factors, including manager brand knowledge and the extent to which strategic information is disseminated among employees. Both theoretical and managerial implications are discussed.

Journal of synchrotron radiation 28(1), 131 - 145 (2021). doi:10.1107/S1600577520013958, In this paper the back-side-illuminated Percival 2-Megapixel (P2M) detector is presented, along with its characterization by means of optical and X-ray photons. For the first time, the response of the system to soft X-rays (250 eV to 1 keV) is presented. The main performance parameters of the first detector are measured, assessing the capabilities in terms of noise, dynamic range and single-photon discrimination capability. Present limitations and coming improvements are discussed., Published by Wiley-Blackwell, [S.l.]

Inputting molecules into chemistry software, such as quantum chemistry packages, currently requires domain expertise, expensive software and/or cumbersome procedures. Leveraging recent breakthroughs in machine learning, we develop ChemPix: an offline, hand-drawn hydrocarbon structure recognition tool designed to remove these barriers. A neural image captioning approach consisting of a convolutional neural network (CNN) encoder and a long short-term memory (LSTM) decoder learned a mapping from photographs of hand-drawn hydrocarbon structures to machine-readable SMILES representations. We generated a large auxiliary training dataset, based on RDKit molecular images, by combining image augmentation, image degradation and background addition. Additionally, a small dataset of ∼600 hand-drawn hydrocarbon chemical structures was crowd-sourced using a phone web application. These datasets were used to train the image-to-SMILES neural network with the goal of maximizing the hand-drawn hydrocarbon recognition accuracy. By forming a committee of the trained neural networks where each network casts one vote for the predicted molecule, we achieved a nearly 10 percentage point improvement of the molecule recognition accuracy and were able to assign a confidence value for the prediction based on the number of agreeing votes. The ensemble model achieved an accuracy of 76% on hand-drawn hydrocarbons, increasing to 86% if the top 3 predictions were considered., Offline recognition of hand-drawn hydrocarbon structures is learned using an image-to-SMILES neural network through the application of synthetic data generation and ensemble learning.

ObjectiveTo estimate the relative frequency of acute medication overuse (AMO) among people with episodic migraine and chronic migraine, to characterize the types of acute medications overused for migraine, and to identify factors associated with AMO.MethodsWe analyzed data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study (ClinicalTrials.gov, NCT01648530), a cross-sectional and longitudinal internet study that included a systematic sampling of the US population. From September 2012 to November 2013, the CaMEO Study respondents participated in different modules to collect data on the clinical course of migraine, family burden, barriers to care, endophenotypes, and comorbidities. Among people who met the criteria for migraine consistent with the International Classification of Headache Disorders, third edition (ICHD-3), we evaluated types and frequency of medications used for headache/migraine, selected comorbidities, and emergency department (ED) and urgent care (UC) use. AMO was defined by days per month of medication use as specified by ICHD-3 criteria for medication overuse headache (MOH) without the requirement for ≥15 monthly headache days (MHDs). Nested, multivariable binary logistic regression modeling was used to identify factors associated with an increased risk of AMO.ResultsOf 16,789 CaMEO respondents with migraine, 2,975 (17.7%) met the AMO criteria. Approximately 67.9% (2,021/2,975) of AMO respondents reported ConclusionsApproximately two-thirds of respondents with AMO reported

To evaluate the healthcare resource use (HRU) and cost of lost productivity due to migraine among Italians with ≥4 monthly migraine days (MMDs), with a focus on those with ≥2 prior preventive treat...

This dataset contains individual subject data for microcirculatory parameters assessed in the present study. Demographic and macrocirculatory parameters are not included at this time due to the present study being part of a larger, partially unpublished project., PMID: 32505603 doi: 10.1053/j.jvca.2020.04.045

OBJECTIVES Neurodevelopmental injury after cardiac surgery using cardiopulmonary bypass (CPB) for congenital heart defects is common, but the mechanism behind this injury is unclear. This study examines the impact of CPB on cerebral mitochondrial reactive oxygen species (ROS) generation and mitochondrial bioenergetics. METHODS Twenty-three piglets (mean weight 4.2 ± 0.5 kg) were placed on CPB for either 1, 2, 3 or 4 h (n = 5 per group) or underwent anaesthesia without CPB (sham, n = 3). Microdialysis was used to measure metabolic markers of ischaemia. At the conclusion of CPB or 4 h of sham, brain tissue was harvested. Utilizing high-resolution respirometry, with simultaneous fluorometric analysis, mitochondrial respiration and ROS were measured. RESULTS There were no significant differences in markers of ischaemia between sham and experimental groups. Sham animals had significantly higher mitochondrial respiration than experimental animals, including maximal oxidative phosphorylation capacity of complex I (OXPHOSCI) (3.25 ± 0.18 vs 4-h CPB: 1.68 ± 0.10, P CONCLUSIONS Even in the absence of local markers of ischaemia, CPB is associated with decreased mitochondrial respiration relative to shams irrespective of duration. Exposure to 4 h of CPB resulted in a significant increase in cerebral mitochondrial ROS formation compared to shorter durations. Further study is needed to improve the understanding of cerebral mitochondrial health and its effects on the pathophysiology of neurological injury following exposure to CPB.

OBJECTIVE We sought to assess factors associated with the frequency of self-reported prescription opioid use in persons with migraine, including demographic variables, comorbidities, headache characteristics, and patterns of consultation. BACKGROUND Despite the dose-dependent effect of opioids on migraine progression and the association with negative outcomes, migraine treatment often includes opioids. The Migraine in America Symptoms and Treatment Study focuses on individuals with migraine who receive prescription acute medications, including those receiving and those not receiving opioids. METHODS This web-based panel survey identified people in the United States with migraine using a validated screener. This analysis stratified people with migraine into 4 groups based on days of monthly opioid use: non-opioid users, ≤3 days, 4-9 days, and ≥10 days per month. RESULTS Of 15,133 respondents with migraine, 4701 (31%) reported acute prescription medication use for headache/migraine in the previous 3 months (mean age 45 years, 71.6% [3367/4701] female), of whom 32.5% (1528/4701) reported opioid use. About one-third of respondents with primary care or neurology consults in the prior 6 months reported receiving an opioid, and more than half of respondents (209/391, 53.5%) with a pain clinic consultation did so. Models compared those using opioids ≤3 days/month (879/4701, 18.7%), 4-9 days/month (304/4701, 6.5%), ≥10 days/month (345/4701, 7.3%) to non-opioid users (3173/4701, 67.5%). Compared to non-opioid users, infrequent users (≤3 days/month) were more likely to be male and less likely to have chronic migraine or to screen positive for anxiety and depression; and frequent opioid users (the 4-9 days/month and the ≥10 days/month groups) were more likely to be male, to smoke, to be obese, to report greater pain interference, to have moderate to severe disability, to have symptoms of anxiety and depression, to use fewer triptans and nonsteroidal anti-inflammatory drugs, and to have poor acute treatment optimization. CONCLUSION Among prescription medication users, this cross-sectional analysis shows that increasing use of prescription opioids is associated with male gender, chronic migraine, more severe disability, anxiety and depression, poor acute treatment optimization, and treatment in a pain clinic.

Brain injury remains a leading cause of morbidity and mortality in children. We evaluated the feasibility of using a pediatric swine model to develop contrast-enhanced ultrasound (CEUS)-based measures of brain perfusion for clinical application in various types of brain injury monitoring. Six-week-old, 10-kg swine (N = 10) were anesthetized, and an acoustic window was created in the right frontal cranium to provide visualization of an oblique coronal plane and bilateral thalami. Ultrasound contrast agent was administered via a femoral venous catheter as a weight-based (0.03 mL/kg) bolus. After localization of the imaging plane, CEUS cine clips were acquired for 90 seconds. Bolus injection of contrast agent provided global visualization of cerebral perfusion and highlighted microvasculature in the brain. Preliminary evaluation of bolus kinetics in piglets showed a central gray nuclei-to-cortex ratio similar to human infants with a steep wash-in that crossed and remained above the 1.0 threshold for most of the enhancement period. We demonstrated the similarity in brain perfusion between piglets and human infants, specifically central gray nuclei-to-cortex ratio, showing preliminary feasibility of its use as a pediatric model of brain perfusion. Contrast-enhanced ultrasound can be performed at the bedside as a minimally invasive procedure, and quantitative CEUS may provide critical information regarding changes in brain perfusion as a result of injury or as a response to therapy.

The coronavirus disease 2019 (COVID-19) pandemic has seen>48 million confirmed cases worldwide as ofNovember 6, 2020.The infection rate amongst children was initially reported to be low, with children constituting only 2% of recorded cases. However, this reflected testing for COVID-19 only when symptomatic or with known close contact with an infected person(1). The purpose of this reportis to describe the characteristics of pediatric patients undergoing universal testing for COVID-19 during routine preoperativescreening at threetertiarychildren's hospitals across the United States.