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Background Minimally invasive repair of pectus excavatum (MIRPE) is associated with less tissue trauma; however, it may result in increased postoperative pain. Pain experience is a known risk factor for the development of posttraumatic stress symptoms, though there are little data on its relationship with long-term psychological outcomes following major surgery in pediatric patients. Aims In this study, we examined the relationship between immediate postoperative pain and psychological outcomes at 2 weeks and three months after discharge in a cohort of pediatric patients who underwent MIRPE. We sought to determine whether immediate postoperative pain levels were associated with ongoing distress related to aspects of surgery at both time points. We were also interested in how psychological symptoms related to persistent pain concerns. Methods Data on patients undergoing MIRPE across 14 institutions were collected as part of the Society for Pediatric Anesthesia Improvement Network (SPAIN). Patients were contacted at 2 weeks and three months following discharge to track pain levels and assess psychological distress using a self-report questionnaire. Patients were grouped into cohorts based on self-report of distress related to aspects of surgery, nonsurgical distress, or absence of distress. Results Analysis revealed that a higher proportion of children reporting ongoing distress related to surgery at both 2 weeks and 3 months experienced higher immediate postoperative pain levels. A subset of patients with complete data sets for 2 weeks and 3 months (N = 76) was further examined. Among the 47 patients who endorsed surgical distress at 2 weeks, 25 (53.2%) continued to endorse surgical distress at 3 months. Additionally, report of surgical distress at 3 months was associated with longer-term postoperative pain. Conclusions Our data suggest that, in patients undergoing MIRPE, the presence of distress at 2 weeks and 3 months may be associated with higher immediate postoperative pain levels.

BACKGROUND Complex cranial vault reconstruction (CCVR) performed to treat craniosynostosis can be associated with significant blood loss, transfusion, and perioperative complications. The aim of this study was to examine the effect of CCVR surgical case volume on perioperative outcomes. We hypothesized that surgical case volume is not associated with differences in perioperative outcomes. The study primary outcome was total perioperative blood donor exposures. Secondary outcomes included the total perioperative transfusion volume, major complications, and intensive care unit and hospital length of stay. METHODS The multicenter Pediatric Surgery Perioperative Registry was queried for infants and children undergoing CCVR between June 2012 and September 2016. Institutions were categorized into low, middle, or high surgical case volume groups based on tertiles of the average number of cases performed per month. Primary and secondary outcomes were analyzed with respect to these groupings. RESULTS The query yielded 1814 CCVR cases from 33 institutions. Demographics were similar among the 3 study groups. An inverse relationship between surgical case volume and total perioperative blood donor exposures was observed (P < .001). The low-volume group had higher perioperative transfusion volumes (P = .02 versus middle; P = .01 versus high). There was no significant relationship between surgical case volume and the incidence of major postoperative complications or hospital length of stay. CONCLUSIONS In this study, low surgical case volumes were associated with increased total blood donor exposures and increased perioperative transfusion volumes. Hospital length of stay was homogeneous in the 3 groups, suggesting a limited overall clinical impact of the observed transfusion outcome differences.

Background Because tobacco use is a major cause of morbidity and mortality worldwide, it is essential to prepare health care providers to assist patients with quitting smoking. Created in 1999, the “Rx for Change” tobacco cessation curriculum was designed to fill an educational gap in cessation training of health professional students. In 2004, a website was launched to host teaching materials and tools to support the efforts of educators and clinicians. Objective The objective of this study was to characterize users and utilization of a website hosting shared teaching materials over a period of 15 years. Methods Data from the Rx for Change website have been collected prospectively since its inception. In this study, end-user data were analyzed to determine user characteristics, how they heard about the website, intended use of the materials, and numbers of logins and file downloads over time. Results Total number of website registrants was 15,576, representing all 50 states in the United States and 94 countries. The most represented discipline was pharmacy (6393/15,505, 41.2%), and nearly half of users were students or residents. The most common source of referral to the website was a faculty member or colleague (33.4%, 2591/7758), and the purpose of enhancing personal knowledge and skills was the most commonly cited intended use of the curricular materials. A total of 259,835 file downloads occurred during the 15-year period, and the most commonly downloaded file type was ancillary handouts. Conclusions The Rx for Change website demonstrated sustained use, providing immediate access to tobacco cessation teaching and practice tools for educators and clinicians over the first 15 years of its existence. The website has a broad interprofessional reach, and the consistent utilization over time and large number of downloads provide evidence for the feasibility and utility of a public-access website hosting teaching materials. The shared curriculum approach averts the need for educators to create their own materials for teaching tobacco cessation to students in the health professions.

Alzheimer's Disease (AD), the leading cause of senile dementia, is a progressive neurodegenerative disorder affecting millions of people worldwide and exerting tremendous socioeconomic burden on all societies. Although definitive diagnosis of AD is often made in the presence of clinical manifestations in late stages, it is now universally believed that AD is a continuum of disease commencing from the preclinical stage with typical neuropathological alterations appearing decades prior to its first symptom, to the prodromal stage with slight symptoms of amnesia (amnestic mild cognitive impairment, aMCI), and then to the terminal stage with extensive loss of basic cognitive functions, i.e., AD-dementia. Positron emission tomography (PET) radiotracers have been developed in a search to meet the increasing clinical need of early detection and treatment monitoring for AD, with reference to the pathophysiological targets in Alzheimer's brain. These include the pathological aggregations of misfolded proteins such as β-amyloid (Aβ) plagues and neurofibrillary tangles (NFTs), impaired neurotransmitter system, neuroinflammation, as well as deficient synaptic vesicles and glucose utilization. In this article we survey the various PET radiotracers available for AD imaging and discuss their clinical applications especially in terms of early detection and cognitive relevance.

Pain management following pediatric tonsillectomy and adenotonsillectomy surgery is challenging and traditionally involves perioperative opioids. However, the recent national opioid shortage compelled anesthesiologists at Bellevue Surgery Center to identify an alternative perioperative analgesic regimen that minimizes opioids yet provides effective pain relief. We assembled an interdisciplinary quality improvement team to trial a series of analgesic protocols using the Plan-Do-Study-Act cycle. Initially, we replaced intraoperative morphine and acetaminophen (M/A protocol) with intraoperative dexmedetomidine and preoperative ibuprofen (D/I protocol). However, when results were not favorable, we rapidly transitioned to intraoperative ketorolac and dexmedetomidine (D/K protocol). The following measures were evaluated using statistical process control chart methodology and interpreted using Shewhart's theory of variation: maximum pain score in the postanesthesia care unit, postoperative morphine rescue rate, postanesthesia care unit length of stay, total anesthesia time, postoperative nausea and vomiting rescue rate, and reoperation rate within 30 days of surgery. There were 333 patients in the M/A protocol, 211 patients in the D/I protocol, and 196 patients in the D/K protocol. With the D/I protocol, there were small increases in maximum pain score and postanesthesia care unit length of stay, but no difference in morphine rescue rate or total anesthesia time compared to the M/A protocol. With the D/K protocol, postoperative pain control and postanesthesia care unit length of stay were similar compared to the M/A protocol. Both the D/I and D/K protocols had reduced nausea and vomiting rescue rates. Reoperation rates were similar between groups. In summary, we identified an intraoperative anesthesia protocol for pediatric tonsillectomy and adenotonsillectomy surgery utilizing dexmedetomidine and ketorolac that provides effective analgesia without increasing recovery times or reoperation rates.

BACKGROUND There are few comparative data on the analgesic options used to manage patients undergoing minimally invasive repair of pectus excavatum (MIRPE). The Society for Pediatric Anesthesia Improvement Network was established to investigate outcomes for procedures where there is significant management variability. For our first study, we established a multicenter observational database to characterize the analgesic strategies used to manage pediatric patients undergoing MIRPE. Outcome data from the participating centers were used to assess the association between analgesic strategy and pain outcomes. METHODS Fourteen institutions enrolled patients from June 2014 through August 2015. Network members agreed to an observational methodology where each institution managed patients based on their institutional standards and protocols. There was no requirement to standardize care. Patients were categorized based on analgesic strategy: epidural catheter (EC), paravertebral catheter (PVC), wound catheter (WC), no regional (NR) analgesia, and intrathecal morphine techniques. Primary outcomes, pain score and opioid consumption by postoperative day (POD), for each technique were compared while adjusting for confounders using multivariable modeling that included 5 covariates: age, sex, number of bars, Haller index, and use of preoperative pain medication. Pain scores were analyzed using repeated-measures analysis of variance with Bonferroni correction. Opioid consumption was analyzed using a multivariable quantile regression. RESULTS Data were collected on 348 patients and categorized based on primary analgesic strategy: EC (122), PVC (57), WC (41), NR (120), and intrathecal morphine (8). Compared to EC, daily median pain scores were higher in patients managed with PVC (POD 0), WC (POD 0, 1, 2, 3), and NR (POD 0, 1, 2), respectively (P < .001-.024 depending on group). Daily opioid requirements were higher in patients managed with PVC (POD 0, 1), WC (POD 0, 1, 2), and NR (POD 0, 1, 2) when compared to patients managed with EC (P < .001). CONCLUSIONS Our data indicate variation in pain management strategies for patients undergoing MIRPE within our network. The results indicate that most patients have mild-to-moderate pain postoperatively regardless of analgesic management. Patients managed with EC had lower pain scores and opioid consumption in the early recovery period compared to other treatment strategies.

Introduction: Various mathematical equations have been proposed to correct QT interval for heart rate (QTc). However, with most formulas, QTc remains dependent on heart rate (HR) especially at low and high HR values. Hypothesis: A spline correction function would perform better than standard mathematical formulas by allowing the data to determine the form of the relationship. Methods: A series of regression models using the generalized additive models for location, scale, and shape framework was applied to 10,000 completely normal electrocardiogram data from the National Health and Nutrition Examination Surveys II and III. Evaluation of the model’s performance was performed using the R 2 coefficient of determination and the root mean squared of the errors between the predicted and observed QTc. The new regression models were compared to the Bazett’s and Fredericia’s formulas, which are the 2 most widely used formulas in clinical practice. Results: When boxplots of the QTc for each formula are plotted, grouped by HR in intervals of 5 beats/minute, QTc determined by the penalized spline regression was almost heart rate independent for both male and female as the slope of the regression line was almost zero (-0.003 for female and -0.001 for male) (Figure 1 A—B). By contrast, QTc by Bazett had a positive correlation (regression slope of 0.86 for female and 0.89 for male) while Fredericia’s had a negative correlation (regression slope of -0.14 for female and -0.13 for male) with HR (Figure 1C—F). In all 3 formulas, there was no significant difference between male and female. Conclusions: A new QTc formula was developed, which is almost independent of HR thereby providing a more accurate estimate of QTc for clinical management. Automatic QTc calculation and percentiles estimation could easily be incorporated in an online calculator or app for easy integration in everyday clinical practice.

Objective This article describes the methodology used for the Pediatric Craniofacial Collaborative Group (PCCG) Consensus Conference. Design This is a novel Consensus Conference of national experts in Pediatric Craniofacial Surgery and Anesthesia, who will follow standards set by the Institute of Medicine and using the Research and Development/University of California, Los Angeles appropriateness method, modeled after the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. Topics related to pediatric craniofacial anesthesia for open cranial vault surgery were divided into twelve subgroups with a systematic review of the literature. Setting A group of 20 content experts met virtually between 2019 and 2020 and will collaborate in their selected topics related to perioperative management for pediatric open cranial vault surgery for craniosynostosis. These groups will also identify where future research is needed. Conclusions Experts in pediatric craniofacial surgery and anesthesiology are developing recommendations on behalf of the Pediatric Craniofacial Collaborative Group for perioperative management of patients undergoing open cranial vault surgery for craniosynostosis and identifying future research priorities.

As noted in Wikipedia,skin in the gamerefers to having ‘incurred risk by being involved in achieving a goal’, where ‘skinis a synecdoche for the person involved, andgameis the metaphor for actions on the field of play under discussion’. For exascale applications under development in the US Department of Energy Exascale Computing Project, nothing could be more apt, with theskinbeing exascale applications and thegamebeing delivering comprehensive science-based computational applications that effectively exploit exascale high-performance computing technologies to provide breakthrough modelling and simulation and data science solutions. These solutions will yield high-confidence insights and answers to the most critical problems and challenges for the USA in scientific discovery, national security, energy assurance, economic competitiveness and advanced healthcare.This article is part of a discussion meeting issue ‘Numerical algorithms for high-performance computational science’.

Background/aims The evolution of Le Fort III and Monobloc procedures with utilization of distraction devices has resulted in shortened surgical times, greater facial advancements, and decreased transfusion requirements. The aim of this observational study was to utilize data from the multicenter Pediatric Craniofacial Surgery Perioperative Registry to present and compare patient characteristics and outcomes in children undergoing midface advancement with distraction osteogenesis. Methods We queried the Pediatric Craniofacial Surgery Perioperative Registry for children undergoing midface advancement involving distractor application from June 2012 to September 2016. Data extracted included demographics, perioperative management, complications, fluid and transfusion volumes, and length of stay. The extracted patient characteristics and perioperative variables were summarized and compared. Results The query yielded 72 cases from 11 institutions: 49 children undergoing Le Fort III and 23 undergoing Monobloc procedures. Monobloc patients were younger, weighed less, and more likely to have tracheostomies along with elevated intracranial pressure. Greater transfusion was observed in the Monobloc group for nearly all of the transfusion outcomes evaluated. Median ICU and hospital length of stay were 2 and 3 days longer, respectively, in the Monobloc group. Perioperative complications were not uncommon, occurring in 18% of patients in the Le Fort III group and 30% in the Monobloc group. Conclusion Monobloc procedures were associated with greater transfusion and longer ICU and hospital length of stay. Perioperative complications were more prevalent in the Monobloc group.

SummaryBackground Antifibrinolytic therapy significantly decreases blood loss and transfusion in pediatric cranial vault reconstructive surgery; however, concern regarding the side effects profile limits clinical use. Aims The aim was to utilize the Pediatric Craniofacial Surgery Perioperative Registry database to identify the safety profile of antifibrinolytic therapy for cranial vault reconstructive surgery by reporting the incidence of adverse events as they relate to exposure to tranexamic acid and aminocaproic acid compared to no exposure to antifibrinolytics. Methods The database was queried for cases of open cranial vault reconstructive surgery. Less invasive procedures such as neuro-endoscopic and spring-mediated cranioplasties were excluded. The outcomes evaluated included any perioperative neurological adverse event including seizures or seizure-like movements and thromboembolic events. Results Thirty-one institutions reported a total of 1638 cases from 2010 to 2015. Total antifibrinolytic administration accounted for 59.5% (tranexamic acid, 36.1% and aminocaproic acid, 23.4%), with 40.5% not receiving any antifibrinolytic. The overall incidence of postoperative seizures or seizure-like movements was 0.6%. No significant difference was detected in the incidence of postoperative seizures between patients receiving tranexamic acid and those receiving aminocaproic acid [the odds ratio for seizures being 0.34 (95% confidence interval: 0.07–1.85) controlling for American Society of Anesthesia (ASA) physical class] nor in patients receiving antifibrinolytics compared to those not administered antifibrinolytics (the odds ratio for seizures being 1.02 (confidence interval 0.29–3.63) controlling for ASA physical class). One complicated patient in the antifibrinolytic group with a femoral venous catheter had a postoperative deep venous thrombosis. Conclusions This is the first report of an incidence of postoperative seizures of 0.6% in pediatric cranial vault reconstructive surgery. There was no significant difference in postoperative seizures or seizure-like events in those patients who received the tranexamic acid or aminocaproic acid vs those that did not. This report provides evidence of the safety profile of antifibrinolytic in children having noncardiac major surgery. Caution should prevail however in using antifibrinolytic in high-risk patients. Antifibrinolytic dosage regimes should be based on pharmacokinetic data avoiding high doses.

Summary Introduction Caudal epidural analgesia (CEA) is a common analgesic technique performed for pediatric penile surgeries; however, it has associated morbidity. The pudendal nerve block (PNB) has been described as an effective analgesic alternative to CEA. Objective In this quality improvement study, we aim to assess the efficacy of PNB as compared to CEA within our ambulatory surgery center (ASC). We demonstrate our initial experience employing PNB for ambulatory pediatric urology procedures. Study design Using retrospective, non-randomized, time-series, observational data, a comparative effectiveness study of CEA and PNB was performed. Patients less than three years old, who underwent circumcision, hypospadias repair, congenital chordee repair, correction of penile angulation/torsion, and buried penis repair with or without scrotoplasty, between January 1, 2015–September 9, 2019 with either CEA or PNB in an ASC at a single institution were included. Standard protocols for local and postoperative analgesia were used. Outcome measures were post anesthesia care unit (PACU) pain scores, morphine rescue rates, and PACU length of stay (LOS). These were analyzed using statistical process control (SPC) charts; standard SPC rules were used to detect special cause variation. Results A total of 999 patients were identified; 746 (74.7%), 172 (17.2%) and 81 (8.1%) received CEA, ultrasound guided PNB (US-PNB) and landmark directed PNB (LD-PNB), respectively. Demographic data was comparable between the three cohorts. There was no special cause variation in the outcome measures between the CEA, US-PNB and LD-PNB cohorts for maximum pain score, morphine rescue rates and PACU LOS. Discussion Pain outcomes and PACU LOS were similar between the CEA, US-PNB and LD-PNB cohorts, suggesting equivalent postoperative pain control between these techniques within our cohort. Previous published data has reported lower postoperative pain scores with PNB as compared to CEA for patients undergoing circumcision and hypospadias repair. Conclusion PNB is non-inferior to CEA for analgesia for pediatric penile surgery, with LD-PNB being as effective as US-PNB. Given the simplicity and documented lower risk profile, PNB may be preferred to CEA for ambulatory pediatric urology procedures. Summary Table . Comparison of Primary and Secondary Outcome Measures Outcome Measure (n) CEA (746) US-PNB (172) LD-PNB (81) Mean of PACU Maximum Pain Score (0–10) 2.50 2.98 2.16 PACU Morphine Administration (%) 2.80 6.94 2.47 PACU Length of Stay (Minutes) 57.77 59.05 57.37 Abbreviations: CEA, caudal epidural anesthesia; PACU post anesthesia care unit; US-PNB, ultrasound guided pudendal nerve block; LD-PNB, landmark directed pudendal nerve block.

A novel error correction scheme, called reset-check-reverse-flag (RCRF), is proposed to improve the reliability of storage class memories (SCMs). RCRF divides the conventional Bose-Chaudhuri-Hocquenghem (BCH) code length into multiple subsections. One flag bit is added to each subsection to correct program errors. By reversing the flag bit and user data, at least one reset error in each subsection can be recovered. A 4 Mbit carbon nanotube (CNT) based nano-random access memory (NRAM) cell array is measured to verify this scheme. During $10^{8}$ write cycles, it is demonstrated that RCRF reduces the program bit error rate (BER) by 50% and only requires 0.4% extra array area for the flag bits. Next, BCH ECC is applied after RCRF to correct the remaining errors. Compared with the conventional BCH ECC-only approach, the proposed combination of RCRF and BCH ECC reduces parity overhead by 35% and ECC decoding latency by 16%. Therefore, RCRF is especially suited for read-intensive types of data storage, such as video and audio. On the other hand, for high endurance applications, RCRF and BCH ECC is also effective to improve the cycling reliability of resistive memories, and 50 times endurance extension is demonstrated for a 50 nm AlxOy resistive RAM (ReRAM) test chip.

Purpose – This paper aims to analyze Public Companies Accounting Oversight Board (PCAOB) inspection reports on audit reports of those inspected accounting firms in Brazil, Russia, India and China (BRIC). In meeting the requirements of the Sarbanes-Oxley Act, the PCAOB conducts inspections on audit reports of firms listed on the New York Stock Exchange. Design/methodology/approach – The reports include those submitted by both the US audit parent firms and their secondary firms located outside the USA. In each PCAOB report, it unravels the nature of audit deficiencies. The focus is on Big Four because they play a dominant role in the marketplace and issuers’ market capitalization. All the seven-year deficiencies are documented since publications of the reports from 2004 to 2012. Findings – Of the 37 reports, 19 (51 per cent) were issued relating to audits conducted by the Big Four. Out of these 19 reports, 10 (53 per cent) contain inspection criticism. These include audit quality and common recurring audit deficiencies. Research limitations/implications – This paper is based solely on those inspection reports published by the PCAOB. Practical implications – The findings have significant implications to audit firms and the audit profession on improving audit quality, firms’ internal control and reports. Originality/value – No known prior research paper is available on the ramifications of the PCAOB’s inspection reports relating to BRIC.

Percutaneous left atrial appendage (LAA) closure is increasingly used to reduce risk of stroke in select patients with Afib. Typically, preprocedural imaging (TEE or cardiac CT) is performed for device selection. This results in multiple procedures, increased risks, patient disengagement. We

Data highlighting the impact of morbid obesity on early outcomes of left atrial appendage occlusion (LAAO) device procedures is extremely limited. Our study aims to evaluate outcomes of in-hospital mortality, length of stay, total hospital cost, and early complications in this patient population.

Purpose: As stereotactic radiosurgery (SRS) and immunotherapy are increasingly used to treat brain metastases, incidence of radiation necrosis (RN) is consequently rising. Differentiating tumor regrowth (TR) from RN is vital in management but difficult to assess using MRI. We hypothesized that tumor methionine levels would be elevated given increased metabolism and high amino acid uptake, whereas RN would increase inflammation marked by upregulated translocator protein (PBR-TSPO), which can be quantified with specific PET tracers. Procedures: We performed a feasibility study to prospectively evaluate [11C]methionine and [11C]PBR28 using PET in 5 patients with 7 previously SRS-treated brain metastases demonstrating regrowth to differentiate TR from RN. Results: Sequential imaging with dual tracers was well-tolerated. [11C]methionine was accurate for detecting pathologically confirmed TR in 7/7 lesions, whereas [11C]PBR28 was only accurate in 3/7 lesions. Tumor PBR-TSPO expression was elevated in both melanoma and lung cancer cells, contributing to lack of specificity of [11C]PBR28-PET. Conclusion: Sequential use of PET tracers is safe and effective. [11C]Methionine was a reliable TR marker, but [11C]PBR28 was not a reliable marker of RN. Studies are needed to determine the causes of post-radiation inflammation and identify specific markers of RN to improve diagnostic imaging.

Background The current incidence of major complications in paediatric craniofacial surgery in North America has not been accurately defined. In this report, the Pediatric Craniofacial Collaborative Group evaluates the incidence and determines the independent predictors of major perioperative complications using a multicentre database. Methods The Pediatric Craniofacial Surgery Perioperative Registry was queried for subjects undergoing complex cranial vault reconstruction surgery over a 5-year period. Major perioperative complications were identified through a structured a priori consensus process. Logistic regression was applied to identify predictors of a major perioperative complication with bootstrapping to evaluate discrimination accuracy and provide internal validity of the multivariable model. Results A total of 1814 patients from 33 institutions in the US and Canada were analysed; 15% were reported to have a major perioperative complication. Multivariable predictors included ASA physical status 3 or 4 (P=0.005), craniofacial syndrome (P=0.008), antifibrinolytic administered (P=0.003), blood product transfusion >50 ml kg–1 (P Conclusions The predictive algorithm can be used as a prognostic tool to risk stratify patients and thereby potentially reduce morbidity and mortality. Craniofacial teams can utilise these predictors of complications to identify high-risk patients. Based on this information, further prospective quality improvement initiatives may decrease complications, and reduce morbidity and mortality.

Introduction: Stroke, a devastating complication in children with Sickle Cell Anemia (SCA), consists of silent cerebral infarct (SCI) and large overt stroke. The current management relies on blood transfusion without the use of thrombolytic agents. However, a recent study showed that co-existent SCA does not impact the safety of tissue plasminogen activator (tPA) treatment. This finding calls for systemic analysis of the effects of thrombolysis in experimental stroke. Hypothesis: We hypothesize that sickle mice are highly vulnerable to hypoxia/ischemia-induced stroke, but respond to tPA-thrombolytic therapy. Methods: Townes sickle mice (knock-in/out mice that express the human α, γ, and sickle-β hemoglobin genes) were subjected to Doppler measurement of the carotid artery and evaluated for their responses to repetitive-mild hypoxia-ischemia (rmHI) and transient hypoxia-ischemia (tHI)-induced stroke at 3 and 6 months of age, respectively. The effects of tPA treatment after tHI in sickle mice were also examined. Results: First, 3-month-old sickle mice of SS genotype with a higher resistive index (RI) in common carotid artery were also prone to rmHI-induced cerebral infarct and mortality. Second, 6-month-old SS mice developed elevated flow velocity and greater RI without stenosis of the carotid artery akin to those previously implicated in large overt stroke in SCA. Finally, 6-month-old SS mice endured 20-min, but manifested enhanced leukocyte and platelet adherence to cerebral blood vessel, as well as, extensive vascular perfusion deficits and fibrin deposition at 4 h post-injury, followed by greatly increased mortality than AA and AS mice at 24 h recovery (p8 for each group). Importantly, intravenous tPA treatment at 0.5 h post-tHI markedly improved vascular reperfusion, mitigated fibrin deposition, and cut the mortality of SS mice by nearly 60%. Conclusions: Humanized sickle mice develop hyper-coagulation and hypersensitivity to HI-induced stroke without large-vessel obstructive vasculopathy at up to 6 months of age. Elevated RI may be an early ultrasonic marker for sickle cell vasculopathy and the risk of SCI in SCA. Future studies are warranted to confirm the therapeutic benefits of thrombolytic stroke therapy in SCA.

The power grid is becoming far more complex as a result of the grid evolution meeting an information revolution. Due to the penetration of smart grid technologies, the grid is evolving as an unprecedented speed and the information infrastructure is fundamentally improved with a large number of smart meters and sensors that produce several orders of magnitude larger amounts of data. How to pull data in, perform analysis, and put information out in a real-time manner is a fundamental challenge in smart grid operation and planning. The future power grid requires high performance computing to be one of the foundational technologies in developing the algorithms and tools for the significantly increased complexity. New techniques and computational capabilities are required to meet the demands for higher reliability and better asset utilization, including advanced algorithms and computing hardware for large-scale modeling, simulation, and analysis. This chapter summarizes the computational challenges in smart grid and the need for high performance computing, and present examples of how high performance computing might be used for future smart grid operation and planning.

Background and Purpose— The effects of lytic stroke therapy in patients with sickle cell anemia are unknown, although a recent study suggested that coexistent sickle cell anemia does not increase the risk of cerebral hemorrhage. This finding calls for systemic analysis of the effects of thrombolytic stroke therapy, first in humanized sickle mice, and then in patients. There is also a need for additional predictive markers of sickle cell anemia-associated vasculopathy. Methods— We used Doppler ultrasound to examine the carotid artery of Townes sickle mice tested their responses to repetitive mild hypoxia–ischemia- and transient hypoxia–ischemia-induced stroke at 3 or 6 months of age, respectively. We also examined the effects of tPA (tissue-type plasminogen activator) treatment in transient hypoxia–ischemia-injured sickle mice. Results— Three-month-old sickle cell (SS) mice showed elevated resistive index in the carotid artery and higher sensitivity to repetitive mild hypoxia–ischemia-induced cerebral infarct. Six-month-old SS mice showed greater resistive index and increased flow velocity without obstructive vasculopathy in the carotid artery. Instead, the cerebral vascular wall in SS mice showed ectopic expression of PAI-1 (plasminogen activator inhibitor-1) and P-selectin, suggesting a proadhesive and prothrombotic propensity. Indeed, SS mice showed enhanced leukocyte and platelet adherence to the cerebral vascular wall, broader fibrin deposition, and higher mortality after transient hypoxia–ischemia. Yet, post-transient hypoxia–ischemia treatment with tPA reduced thrombosis and mortality in SS mice. Conclusions— Sickle mice are sensitive to hypoxia/ischemia-induced cerebral infarct but benefit from thrombolytic treatment. An increased resistive index in carotid arteries may be an early marker of sickle cell vasculopathy.

Editorial for Journal of Interventional Cardiac Electrophysiology (JICE) In the last decade, increasing evidence has emerged for a genetic predisposition to atrial fibrillation (AF). In 2003, Mayo Clinic investigators showed that 15 % of patients with lone AF had a positive family history of the condition [1]. Subsequent epidemiological studies observed that the odds of developing AF increased three to five-fold depending on the age of onset of AF in a parent [2, 3]. Furthermore, numerous genes associated with AF have been identified using positional cloning and linkage analyses, candidate gene and exome-sequencing approaches [4]. In 2003, the first gene (KCNQ1) encoding the delayed cardiac rectifier potassium channel (IKs) was linked with familial AF. [5] Mutations encoding cardiac ion channels (Na+, K+ and Ca2+), gap junction proteins (connexins) and signaling molecules (nucleoporin 155 [NUP155], natriuretic peptide precursor A [NPPA]) have been described in Mendelian forms of AF. However, the extent to which genetic factors contribute to the more common forms of AF remained unclear until the advent of genome-wide association studies (GWAS). While many patients with AF have known risk factors, e.g., hypertension, the majority of the patients in the general population with those risk factors do not develop AF. Thus, one concept proposed is that common genetic variants increase susceptibility to AF in some individuals with other identifiable risk factors—a basis for the “two-hit” hypothesis [4]. Recent advances in next generation sequencing have now made it possible to assay hundreds of thousands of single nucleotide polymorphisms (SNPs) spread across the entire human genome. In 2007, the first GWAS of AF identified a strong association between AF and a haplotype block on chromosome (chr) 4q25 [6]. Within this locus, two non-coding SNPs were independently associated with AF, and these findings were replicated in two populations of European descent and one of Asian descent [6]. Although the mechanism for this observed association still remains unclear, the locus is adjacent to the paired-like homeodomain transcription factor 2 (PITX2) which is important for pulmonary vein (PV) development [7]. This association has been independently replicated, and we also showed that the association also holds in post-cardiac surgery AF. [8] Two additional loci on chr16q22 [9] and chr1q21 [10] were identified, and a meta-analysis of AF GWAS in 2012, not only validated these three SNPs but also identified and replicated six additional novel AF susceptibility alleles [11]. More recently, the AFGen Consortium has identified five more novel AF loci [12]. Although GWAS have identified common SNPs associated with AF and provided insights into underlying genetic mechanisms, recent studies suggest that these risk alleles may also identify genetic subtypes of AF with differential response to therapy [4]. A 2012 study examined whether symptomatic response to antiarrhythmic drug (AAD) therapy is modulated by the three common AF susceptibility loci on chr4q25 (near PITX2), 16q22 (in ZFXH3), and 1q21 (in KCNN3) in 478 (discovery cohort) and 198 (validation cohort), age- and gender-matched European Caucasian patients [13]. Successful response to rhythm control therapy was defined as maintenance of the same AAD for a minimum of 6 months with ≥75 % reduction in AF symptoms. While clinical variables such as age, hypertension, and lone AF failed to predict maintenance of sinus rhythm, rs10033464 (chr4q25) SNP did predict successful rhythm control in patients with typical AF carrying the wild-type (WT) allele with an odds ratio of 4.7 (95 % CI 1.83 to 12, P

BACKGROUND The North American Pediatric Craniofacial Collaborative Group (PCCG) established the Pediatric Craniofacial Surgery Perioperative Registry to evaluate outcomes in infants and children undergoing craniosynostosis repair. The goal of this multicenter study was to utilize this registry to assess differences in blood utilization, intensive care unit (ICU) utilization, duration of hospitalization, and perioperative complications between endoscopic-assisted (ESC) and open repair in infants with craniosynostosis. We hypothesized that advantages of ESC from single-center studies would be validated based on combined data from a large multicenter registry. METHODS Thirty-one institutions contributed data from June 2012 to September 2015. We analyzed 1382 infants younger than 12 months undergoing open (anterior and/or posterior cranial vault reconstruction, modified-Pi procedure, or strip craniectomy) or endoscopic craniectomy. The primary outcomes included transfusion data, ICU utilization, hospital length of stay, and perioperative complications; secondary outcomes included anesthesia and surgical duration. Comparison of unmatched groups (ESC: N = 311, open repair: N = 1071) and propensity score 2:1 matched groups (ESC: N = 311, open repair: N = 622) were performed by conditional logistic regression analysis. RESULTS Imbalances in baseline age and weight are inherent due to surgical selection criteria for ESC. Quality of propensity score matching in balancing age and weight between ESC and open groups was assessed by quintiles of the propensity scores. Analysis of matched groups confirmed significantly reduced utilization of blood (26% vs 81%, P < .001) and coagulation (3% vs 16%, P < .001) products in the ESC group compared to the open group. Median blood donor exposure (0 vs 1), anesthesia (168 vs 248 minutes) and surgical duration (70 vs 130 minutes), days in ICU (0 vs 2), and hospital length of stay (2 vs 4) were all significantly lower in the ESC group (all P < .001). Median volume of red blood cell administered was significantly lower in ESC (19.6 vs 26.9 mL/kg, P = .035), with a difference of approximately 7 mL/kg less for the ESC (95% confidence interval for the difference, 3-12 mL/kg), whereas the median volume of coagulation products was not significantly different between the 2 groups (21.2 vs 24.6 mL/kg, P = .73). Incidence of complications including hypotension requiring treatment with vasoactive agents (3% vs 4%), venous air embolism (1%), and hypothermia, defined as

Age is the primary risk factor for osteoarthritis (OA), yet surgical OA mouse models such as destabilization of the medial meniscus (DMM) used for evaluating disease-modifying OA targets are frequently performed on young adult mice only. This study investigates how age affects cartilage and subchondral bone changes in mouse joints following DMM. DMM was performed on male C57BL/6 mice at 4 months (4 M), 12 months (12 M) and 19+ months (19 M+) and on females at 12 M and 18 M+. Two months after surgery, operated and unoperated contralateral knees were harvested and evaluated using cartilage histology scores and μCT quantification of subchondral bone plate thickness and osteophyte formation. The 12 M and 19 M+ male mice developed more cartilage erosions and thicker subchondral bone plates after DMM than 4 M males. The size of osteophytes trended up with age, while the bone volume fraction was significantly higher in the 19 M+ group. Furthermore, 12 M females developed milder OA than males as indicated by less cartilage degradation, less subchondral bone plate sclerosis and smaller osteophytes. Our results reveal distinct age/gender-dependent structural changes in joint cartilage and subchondral bone post-DMM, facilitating more thoughtful selection of murine age/gender when using this surgical technique for translational OA research.

Conventional permanent His Bundle pacing (PHBP) can be associated with high fluoroscopy exposure. The objective of this study was to assess the feasibility and safety of performing low fluoroscopy PHBP utilizing 3D electro-anatomic mapping (EAM) and compare outcomes with conventional fluoroscopic

We describe the case of a 63-year-old man with a known murmur who presented with a 4-month history of intermittent fever and a progressive reduction in energy level after a transrectal prostate biopsy (TRPB). He subsequently presented with acute heart failure secondary to aortic valve cusp rupture caused by endocarditis and underwent urgent aortic valve surgery. The 2008 American College of Cardiology/American Heart Association Guideline update on infective endocarditis has narrowed the use of antibiotic prophylaxis before most accepted dental procedures and continues to recommend against prophylaxis before genitourinary or gastrointestinal procedures. In contrast, the American Urological Association recommends the use of fluoroquinolones for the prevention of transrectal ultrasound–derived infectious complications. Notably, TRPB is associated with a high frequency of bacteremia and bacteriuria. In our case, an antibiotic course before the procedure and a more meticulous medical work-up after febrile illness might have mitigated the patient's catastrophic medical presentation.

Background Poor bone quality, increased fracture risks, and impaired bone healing are orthopedic comorbidities of type 1 diabetes (T1DM). Standard osteogenic growth factor treatments are inadequate in fully rescuing retarded healing of traumatic T1DM long bone injuries where both periosteal and bone marrow niches are disrupted. We test the hypotheses that osteogenesis of bone marrow-derived stromal cells (BMSCs) and periosteum-derived cells (PDCs), two critical skeletal progenitors in long bone healing, are both impaired in T1DM and that they respond differentially to osteogenic bone morphogenetic proteins (BMPs) and/or insulin-like growth factor-1 (IGF-1) rescue. Methods BMSCs and PDCs were isolated from Biobreeding Diabetes Prone/Worcester rats acquiring T1DM and normal Wistar rats. Proliferation, osteogenesis, and adipogenesis of the diabetic progenitors were compared with normal controls. Responses of diabetic progenitors to osteogenesis rescue by rhBMP-2/7 heterodimer (45 or 300 ng/ml) and/or rhIGF-1 (15 or 100 ng/ml) in normal and high glucose cultures were examined by alizarin red staining and qPCR. Results Diabetic BMSCs and PDCs proliferated slower and underwent poorer osteogenesis than nondiabetic controls, and these impairments were exacerbated in high glucose cultures. Osteogenesis of diabetic PDCs was rescued by rhBMP-2/7 or rhBMP-2/7 + rhIGF-1 in both normal and high glucose cultures in a dose-dependent manner. Diabetic BMSCs, however, only responded to 300 ng/nl rhBMP-2/7 with/without 100 ng/ml rhIGF-1 in normal but not high glucose osteogenic culture. IGF-1 alone was insufficient in rescuing the osteogenesis of either diabetic progenitor. Supplementing rhBMP-2/7 in high glucose osteogenic culture significantly enhanced gene expressions of type 1 collagen (Col 1), osteocalcin (OCN), and glucose transporter 1 (GLUT1) while suppressing that of adipogenic marker peroxisome proliferator-activated receptor gamma (PPARγ) in diabetic PDCs. The same treatment in high glucose culture only resulted in a moderate increase in Col 1, but no significant changes in OCN or GLUT1 expressions in diabetic BMSCs. Conclusions This study demonstrates more effective osteogenesis rescue of diabetic PDCs than BMSCs by rhBMP-2/7 with/without rhIGF-1 in a hyperglycemia environment, underscoring the necessity to tailor biochemical therapeutics to specific skeletal progenitor niches. Our data also suggest potential benefits of combining growth factor treatment with blood glucose management to optimize orthopedic therapeutic outcomes for T1DM patients.

Over the last decade, tremendous progress has been made in defining the genetic architecture of atrial fibrillation (AF). This has in part been driven by poor understanding of the pathophysiology of AF, limitations of current therapies and failure to target therapies to the underlying mechanisms.Genetic approaches to AF have identified mutations encoding cardiac ion channels, and signaling proteins linked with AF and genome-wide association studies have uncovered common genetic variants modulating AF risk. These studies have provided important insights into the underlying mechanisms of AF and defined responses to therapies. Common AF-risk alleles at the chromosome 4q25 locus modulate response to antiarrhythmic drugs, electrical cardioversion and catheter ablation. While the translation of these discoveries to the bedside care of individual patients has been limited, emerging evidence supports the hypothesis that genotype-directed approaches that target the underlying mechanisms of AF may not only improve therapeutic efficacy but also minimize adverse effects. Expert commentary: There is an urgent need for randomized controlled trials that are genotype-based for the treatment of AF. Nonetheless, emerging data suggest that selecting therapies for AF that are genotype-directed may soon be upon us.

Carbon Nanotube (CNT) memory has a simple structure, low voltage, low current, and fast switching mechanism, and endurance up to 1012 cycles has been demonstrated [1]. In order to optimize set and reset algorithms and understand the mechanisms of CNT reliability, this work studies the CNT after 107 endurance cycles for different combinations of set and reset endurance voltages. It is confirmed that set and reset cycling voltages affect the count and ratio of set and reset errors after 107. Based on measurement of a 6Mb test chip, the endurance condition in which the set voltage is lower than the reset voltage, gives the best cycling.

The increasing capabilities and decreasing cost of information and communication technologies (ICTs) are enabling new categories of vehicular telematics applications, such as wireless drive-through (WDT) services, in which an external service provider provides services to in-vehicle occupants via a wireless connection. Most telematics systems rely on proprietary protocols for data exchange between an in-vehicle client and its external counterpart in individual applications, making it difficult to share data-exchange methods among applications. Sharing data-exchange methods is important because it allows a rapid return on ICT investments. In this paper, we study the data-modeling issues for data exchange between an in-vehicle client and its service provider for WDT services. We present a novel data model that captures the main characteristics of data exchange for the WDT application family, using a formal mathematical representation and an intuitive graphical representation. We show that the proposed data model provides generality for such data exchange. In addition, we propose several optimization techniques based on the data model to minimize user interaction so that a good usability can be achieved. Our simulations and analysis demonstrate that the proposed data model and relevant optimization techniques are promising in supporting efficient WDT applications.

His bundle pacing (HBP) has recently shown to be effective for cardiac resynchronization therapy (CRT) by overcoming bundle branch block (BBB). We analyzed paced QRS duration (QRSd) among patients receiving HBP for CRT in comparison to patients who received traditional biventricular (BiV) pacing for

Purpose – The purpose of this paper is to investigate the effects of class action litigation on firms' cost of equity capital.Design/methodology/approach – The paper uses three different models to estimate the cost of equity capital. To separate the impact of lawsuit filings on the cost of equity capital from that of the revelation event, a sample of lawsuits with a long lag between the disclosure events and filing dates was analyzed. Also, a comparison group study was conducted to illustrate the distinct impact of a lawsuit filing on the defendant firm's cost of equity capital. Finally, a multivariate analysis was used to examine the factors that affect the magnitude of such impact.Findings – The paper finds that filing of a class action lawsuit results in a significant increase in the defendant firm's cost of equity capital incremental to the effect of the disclosure event. Additionally, increases in the cost of equity capital after the lawsuit filings are higher when the lawsuits involve generally acce...

Manuscript Type: Empirical Research Question/Issue: This study examines the determinants of forming a governance committee and whether such a committee constrains managerial opportunism. Research Findings/Insights: This study examines a sample of S&P 1,500 firms over the period of 1996 to 2002. It finds that firms with a larger, more independent, and more active board, higher agency costs (as indicated by lower managerial ownership and lower takeover vulnerability), and past occurrence of class-action lawsuits are more likely to voluntarily form a governance committee. This study also provides evidence that having a governance committee brings real consequences in that it constrains managerial opportunism by reducing aggressive financial reporting. Theoretical/Academic Implications: Consistent with substitution theory, this study documents that a firm is more likely to form a governance committee to compensate for its severe agency problems. It also demonstrates that delegating some corporate governance duties to a specific board committee could improve the effectiveness of board monitoring. Practitioner/Policy Implications: This study provides insights to regulators who are interested in regulating board structure. It suggests that whether a firm needs to form a governance committee is endogenously determined by the firm's characteristics when the firm has an independent board. In addition, this study documents that a voluntarily formed governance committee is able to mitigate agency costs in the form of constraining managerial accounting discretion.

CNT (Carbon Nanotube) based memory (NRAM) demonstrates a beneficial scaling effect related to the patterned area of the CNT region, such that the scaled feature shows an improvement in ON/OFF resistance ratio (to ~10,000x and improved data retention relative to the original feature dimensions.

1547-5271/$-see front matter B 2014 Heart Rhythm Society. All rights reserved. PLSVC to the right superior pulmonary vein. She underwent electrophysiology study and ablation of an atypical right atrial flutter. The pre-procedure cardiac magnetic resonance imaging demonstrated shunt from the PLSVC into the right superior pulmonary vein with a Qp/Qs ratio of 1.5:1 (Figure 1A, white arrow). Electroanatomic mapping confirmed the presence of a PLSVC (Figure 1B). In order to exclude left atrial appendage (LAA) thrombus and to examine the presence of a right to left shunt, we took advantage of the coronary sinus system with its anatomical proximity to the LAA (Figures 1C and 1D). The intracardiac ultrasound catheter was advanced via the coronary sinus into the great cardiac vein (Figures 1C and 1D, yellow star). This

implantation of a BVS, an emerging effective treatment for de-novo coronary artery disease [3] allowed for satisfactory treatment of both the ISR and the in-segment disease. Figure legend: Optical coherence tomography (OCT) appearance pre-implantation of a bioresorbable vascular scaffold (BVS) with significant neointimal proliferation over two layers of stent struts following pre-dilatation to facilitate adequate contrast flow for OCT (Panel A) with significant atheroma also seen at the proximal nonstented segment (Panel B) with balloon related dissection also present. Absorb 3.5 × 18 mm BVS with adequate BVS expansion and apposition over the two previously placed layers of metallic stent struts (Panels C, D and zoomed up image Panel E). Baseline angiographic image before any balloon dilatation (Panel F) shows severe in-stent and significant in-segment stenosis. Final angiographic appearance post BVS was satisfactory (Panel G).

FINAL PROJECT REPORT LOAD MODELING TRANSMISSION RESEARCH Prepared for CIEE By: Lawrence Berkeley National Laboratory Project Manager: Bernard Lesieutre Authors: Richard Bravo, Robert Yinger, Dave Chassin, Henry Huang, Ning Lu, Ian Hiskens, Giri Venkataramanan Date: March, 2010 A CIEE Report

It is well known that the noise in magnetic resonance (MR) magnitude images obeys a Rician distribution. Denoising of MR images is of importance for clinical diagnosis and computerized analysis, such as tissue classification, segmentation, and registration. We propose a post-acquisition denoising algorithm in an attempt to automatically remove the random fluctuations and bias introduced by Rician noise. It replaces the intensity value on each pixel with an average value weighted by the geometric, radiometric, and median-metric components between neighboring pixels associated with an entropy function. Moreover, fuzzy functions are introduced to adaptively compute the parameters in terms of local intensity variations. The contrast-enhanced results indicate that this new filter outperformed several existing methods in providing greater noise reduction and clearer structure boundaries in MR images.

Background Children with asthma most often have associated allergy, and peanut allergy with asthma is more common in children whose parents have asthma. It is not clear how common peanut allergy is among these children. The St. John’s cohort, India has found 6.2% peanut sensitivity children whose mothers have asthma. Children are at greater risk for severe life threatening reactions and hospitalization. Materials and methods The SAGE cohort is a study of children born in 1995 in Manitoba. We created a nested case-control cohort of 723 children for asthma and allergy at 8 years of age. Atopy was defined as having at least one positive skin test, to common inhalantsand to peanut (wheal diameter≥3 mm.) Chi-square test and Fisher’ se xact test was applied, the likelihood (odds ratio, OR) of parental asthma of non-peanut allergic children compared to parental asthma of peanut sensitized children was determined.

A 4Mbit nonvolatile memory with a Carbon Nanotube (CNT) storage element has been manufactured in a 0.25 µm CMOS process at a production fab. The CNT storage element is integrated in BEOL, requires minimal additional processing steps, and only a single additional mask. The memory can be RESET in 50 nanoseconds and SET in 500 nanoseconds. Demonstrated read access time of the development vehicle is 50 nanoseconds. Write endurance is in excess of 10,000 cycles, and robust data retention has been demonstrated. The CNT storage element is scalable to

A 4Mbit nonvolatile memory with a Carbon Nanotube (CNT) storage element has been manufactured in a 0.25 µm CMOS process at a production fab. The CNT storage element is integrated in BEOL, requires minimal additional processing steps, and only a single additional mask. The memory can be RESET in 50 nanoseconds and SET in 500 nanoseconds. Demonstrated read access time of the development vehicle is 50 nanoseconds. Write endurance is in excess of 10,000 cycles, and robust data retention has been demonstrated. The CNT storage element is scalable to

Power system mode shapes are a key indication of how dynamic components participate in low-frequency oscillations. Traditionally, mode shapes are calculated from a linearized dynamic model. For large-scale power systems, obtaining accurate dynamic models is very difficult. Therefore, measurement-based mode shape estimation methods have certain advantages, especially for the application of real-time small signal stability monitoring. In this paper, a measurement-based mode shape identification method is proposed. The general relationship between transfer function (TF) and mode shape is derived. As an example, a least square (LS) method is implemented to estimate mode shape using an autoregressive exogenous (ARX) model. The performance of the proposed method is evaluated by Monte-Carlo studies using simulation data from a 17-machine model. The results indicate the validity of the proposed method in estimating mode shapes with reasonably good accuracy.

This paper describes an advanced modeling facility for system and software design that is being constructed at the Ford Research and Innovation Center. This facility is intended to address the growing complexity of automotive embedded software and the resulting issues for vehicle development. Software complexity is expected to grow at a significantly higher rate in the near future as vehicle systems begin to interact with external software based systems to provide significant new capabilities in both the infotainment and the safety areas. Increased complexity will require a broader range of modeling capabilities than just functional/behavioral modeling. Our recent experience with the latter has shown substantial benefits for the product development process, and we expect that the more comprehensive modeling process described here will bring even greater benefits.

To navigate successfully, a mobile robot must be able to estimate the spatial relationships of the objects of interest in its environment accurately. The main advantage of a bearing-only Simultaneous Localization and Mapping (SLAM) system is that it requires only a cheap vision sensor to enable a mobile robot to gain knowledge of its environment and navigate. In this paper, we focus on the representation of the spatial uncertainty of landmarks caused by sensor noise. We follow a principled approach for computing the Probability Density Functions (PDFs) of landmark positions when an initial observation is made. We characterize the PDF p(r, α) of a landmark position expressed in polar coordinates when r and α are independent, and the marginal probability p(r) of the PDF is constrained to be uniform.