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Presbyphonia negatively impacts quality of life in patients with age-related voice changes. A proof-of-concept study showed promise for high vocal intensity exercise to treat presbyphonia, which became the basis for a novel intervention for age-related voice changes known as Phonation Resistance Training Exercises (PhoRTE). Expiratory Muscle Strength Training (EMST) has also been proposed as an additional intervention to target and strengthen the aging respiratory system; however, EMST has undergone limited evaluation as an adjunct treatment for elderly patients undergoing voice therapy for presbyphonia. This study determined if the addition of EMST to PhoRTE voice therapy (PhoRTE + EMST) is at least as effective at voice improvement as PhoRTE alone.Prospective, randomized, controlled, single-blinded, non-inferiority.Participants aged 55 years or older with a diagnosis of vocal fold atrophy were randomized to complete PhoRTE therapy or PhoRTE + EMST. The primary outcome was change in Voice Handicap Index-10 (VHI-10). Secondary outcomes included the Aging Voice Index, maximum expiratory pressure, and acoustic and aerodynamic measures of voice. Repeated measures linear mixed models were constructed to analyze outcomes at a significance level of α = 0.10.Twenty-six participants were recruited for the study, and 24 participants were randomized to either treatment arm. Sixteen participants completed the entire study. Both treatment arms showed statistically significant and clinically meaningful improvements in VHI-10 (PhoRTE mean [M] = -8.20, P0.001; PhoRTE + EMST M = -9.58, P0.001), and PhoRTE + EMST was noninferior to PhoRTE alone (P = 0.069). Both groups experienced a statistically significant pre-post treatment decrease (improvement) in AVI scores (PhoRTE M = -18.40, P = 0.004; PhoRTE + EMST M = -16.28, P = 0.005). PhoRTE+EMST had statistically significantly greater changes in maximum expiratory pressure compared to PhoRTE alone (PhoRTE M = 8.24 cm HThis study demonstrates that voice therapy targeting high vocal intensity exercise (eg, PhoRTE) and EMST can play a role in improving voice outcomes for patients with presbyphonia.

Summary Objective Semioccluded vocal tract (SOVT) exercises are routinely included in many voice therapy programs because they have been shown to improve acoustic, aerodynamic, and patient-reported voice outcomes. One limitation of the traditional SOVT exercise is that the nature of phonation through straws or semioccluded oral postures allows only for single phoneme production. A variably occluded facemask (VOFM) allows for use of articulated connected speech beyond the production of single phonemes, while still providing occlusion and, presumably, the vocal efficiency benefits that arise from it. This study reports on the effect of time duration of phonation with a variably occluded facemask on voice outcomes in patients with voice disorders. Design Prospective, randomized cohort study. Methods Fifteen patients with voice disorders phonated for 5 minutes through a VOFM with diameter openings of 3.2, 6.4, and 9.6 mm. Acoustic and aerodynamic voice measures were collected before and after each occlusion trial. These results were compared to a historical patient group that received the same phonation training for 2 minutes. Results Positive effect sizes were found for acoustic and aerodynamic improvements for all patients for at least one occlusion diameter. Effect sizes for aerodynamic outcomes were greater in the 5-minute conditions for both the 9.6- and 6.4-mm occlusions than the 2-minute condition. Effect sizes for acoustic outcomes were greater in the 5 minute than 2-minute trial for the 9.6- and 6.4-mm occlusion diameter, but greater in the 2 minute than 5-minute trial for 3.2-mm diameter. Discussion This study provides evidence that all three occlusion sizes may elicit beneficial changes for different patients; however, 5 minutes of phonation into a facemask with end occlusion of 6.4-mm diameter results in improved acoustic and aerodynamic voice outcomes for many patients with voice disorders. Future studies should further explore phonatory physiologic changes of the VOFM in a larger sample of patients and translate effects into clinical treatment for patients with voice disorders.

Methods to quantify biological aging are emerging as new measurement tools for epidemiology and population science and have been proposed as surrogate measures for healthy lifespan extension in geroscience clinical trials. Publicly available software packages to compute biological aging measurements from DNA methylation data have accelerated dissemination of these measures and generated rapid gains in knowledge about how different measures perform in a range of datasets. Biological age measures derived from blood chemistry data were introduced at the same time as the DNA methylation measures and, in multiple studies, demonstrate superior performance to these measures in prediction of healthy lifespan. However, their dissemination has been slow by comparison, resulting in a significant gap in knowledge. We developed a software package to help address this knowledge gap. The BioAge R package, available for download at GitHub (http://github.com/dayoonkwon/BioAge), implements three published methods to quantify biological aging based on analysis of chronological age and mortality risk: Klemera-Doubal biological age, PhenoAge, and homeostatic dysregulation. The package allows users to parametrize measurement algorithms using custom sets of biomarkers, to compare the resulting measurements to published versions of the Klemera-Doubal method and PhenoAge algorithms, and to score the measurements in new datasets. We applied BioAge to safety lab data from the CALERIE™ randomized controlled trial, the first-ever human trial of long-term calorie restriction in healthy, non-obese adults, to test effects of intervention on biological aging. Results contribute evidence that CALERIE intervention slowed biological aging. BioAge is a toolkit to facilitate measurement of biological age for geroscience. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-021-00480-5.

Background Dysregulation of some metabolic factors increases the risk of dementia. It remains unclear if overall metabolic dysregulation, or only certain components, contribute to cognitive aging and if these associations are sex specific. Methods Data from the 2006–2016 waves of the Health and Retirement Study (HRS) was used to analyze 7 103 participants aged 65 and older at baseline (58% women). We created a metabolic-dysregulation risk score (MDRS) composed of blood pressure/hypertension status, glycosylated hemoglobin (HbA1c)/diabetes status, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and waist circumference, and assessed cognitive trajectories from repeated measures of the HRS-Telephone Interview for Cognitive Status (HRS-TICS) over 10 years of follow-up. Linear mixed-effects models estimated associations between MDRS or individual metabolic factors (biomarkers) with mean and change in HRS-TICS scores and assessed sex-modification of these associations. Results Participants with higher MDRSs had lower mean HRS-TICS scores, but there were no statistically significant differences in rate of decline. Sex stratification showed this association was present for women only. MDRS biomarkers revealed heterogeneity in the strength and direction of associations with HRS-TICS. Lower HRS-TICS levels were associated with hypertension, higher HbA1c/diabetes, and lower HDL-C and TC, whereas faster rate of cognitive decline was associated with hypertension, higher HbA1c/diabetes, and higher TC. Participants with higher HbA1c/diabetes presented worse cognitive trajectories. Sex differences indicated that women with higher HbA1c/diabetes to have lower HRS-TICS levels, whereas hypertensive males presented better cognitive trajectory. Conclusions Our results demonstrate that metabolic dysregulation is more strongly associated with cognition in women compared with men, though sex differences vary by individual biomarker.

OBJECTIVE: To understand whether genetic risk for attention-deficit/hyperactivity disorder (ADHD) is associated with the course of the disorder across childhood and into young adulthood.METHOD: Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a population-based birth cohort of 2,232 twins. ADHD was assessed at ages 5, 7, 10, and 12 with mother- and teacher-reports and at age 18 with self-report. Polygenic risk scores (PRSs) were created using a genome-wide association study of ADHD case status. Associations with PRS were examined at multiple points in childhood and longitudinally from early childhood to adolescence. We investigated ADHD PRS and course to young adulthood, as reflected by ADHD remission, persistence, and late onset.RESULTS: Participants with higher ADHD PRSs had increased risk for meeting ADHD diagnostic criteria (odds ratios ranging from 1.17 at age 10 to 1.54 at age 12) and for elevated symptoms at ages 5, 7, 10, and 12. Higher PRS was longitudinally associated with more hyperactivity/impulsivity (incidence rate ratio = 1.18) and inattention (incidence rate ratio = 1.14) from age 5 to age 12. In young adulthood, participants with persistent ADHD exhibited the highest PRS (mean PRS = 0.37), followed by participants with remission (mean PRS = 0.21); both groups had higher PRS than controls (mean PRS = -0.03), but did not significantly differ from one another. Participants with late-onset ADHD did not show elevated PRS for ADHD, depression, alcohol dependence, or marijuana use disorder.CONCLUSION: Genetic risk scores derived from case-control genome-wide association studies may have relevance not only for incidence of mental health disorders, but also for understanding the longitudinal course of mental health disorders.

Objectives: Extensive literature exists documenting disparities in access to healthcare for patients with lower socioeconomic status (SES). The objective of this study was to examine access disparities and differences in surgical wait times in children with the most common pediatric otolaryngologic surgery, tympanostomy tubes (TT). Methods: A retrospective cohort study was performed at a tertiary children’s hospital. Children ages Results: A total of 969 patients were included. Average age at surgery was 2.11 years. Almost 90% were white and 67.5% had private insurance. Patients with public insurance, ≥1 no-show appointment, and who lived in zip codes with the median income below the United States median had a longer period from otologic consult and preoperative clinic to TT, but no differences were seen in race. Those with public insurance had their surgery at an older age than those with private insurance ( P Conclusions: Lower SES is associated with chronic otitis media with effusion and a longer wait time from otologic consult and preoperative clinic to TT placement. By being transparent in socioeconomic disparities, we can begin to expose systemic problems and move forward with interventions. Level of Evidence: 4

Background Loneliness and social isolation are emerging public health challenges for aging populations. Methods We followed N = 11 302 U.S. Health and Retirement Study participants aged 50–95 from 2006 to 2014 to measure persistence of experiences of loneliness and exposure to social isolation. We tested associations of longitudinal loneliness and social isolation phenotypes with disability, morbidity, mortality, and biological aging through 2018. Results During follow-up, 18% of older adults met criteria for loneliness, with 6% meeting criteria at 2 or more follow-up assessments. For social isolation, these fractions were 21% and 8%. Health and Retirement Study participants who experienced loneliness and were exposed to social isolation were at increased risk for disease, disability, and mortality. Those experiencing persistent loneliness were at a 57% increased hazard of mortality compared to those who never experienced loneliness. For social isolation, the increase was 28%. Effect sizes were somewhat larger for counts of prevalent activity limitations and somewhat smaller for counts of prevalent chronic diseases. Covariate adjustment for socioeconomic and psychological risks attenuated but did not fully explain associations. Older adults who experienced loneliness and were exposed to social isolation also exhibited physiological indications of advanced biological aging (Cohen’s d for persistent loneliness and social isolation = 0.26 and 0.21, respectively). For loneliness, but not social isolation, persistence was associated with increased risk. Conclusions Deficits in social connectedness prevalent in a national sample of U.S. older adults were associated with morbidity, disability, and mortality and with more advanced biological aging. Bolstering social connectedness to interrupt experiences of loneliness may promote healthy aging.

Objective: To analyze trends in otolaryngology consultations and provide algorithms to guide management during the COVID-19 pandemic. Methods: A retrospective cohort study at a single institution tertiary care hospital. A total of 95 otolaryngology consultations were performed from March 1, 2020 to April 26, 2020 (COVID-era) and 363 were performed from September 1, 2019 to February 29, 2020 (pre-COVID-era) at the UPMC Oakland campus. Data collected included patient demographics, COVID-19 status, reason for consult, location of consult, type of consult, procedures performed, need for surgical intervention, length of hospital stay and recommended follow up. Results: Patient populations in the pre-COVID-era and COVID-era were similar in terms of their distribution of demographics and chief complaints. Craniofacial trauma was the most common reason for consultation in both periods, followed by vocal fold and airway-related consults. We saw a 21.5% decrease in the rate of consults seen per month during the COVID-era compared to the 6 months prior. Review of trends in the consult workflow allowed for development of several algorithms to safely approach otolaryngology consults during the COVID-19 pandemic. Conclusions: Otolaryngology consultations provide valuable services to inpatients and patients in the emergency department ranging from evaluation of routine symptoms to critical airways. Systematic otolaryngology consult service modifications are required in order to reduce risk of exposure to healthcare providers while providing comprehensive patient care.

Advanced practice provider (APP) employment is becoming common in pediatric otolaryngology practices, though few studies have evaluated the consequences that APP-led clinics have on access to care. The objectives of this study were: 1) to investigate whether access to bilateral myringotomy with tympanostomy tube placement (BMT) for recurrent acute otitis media (RAOM) differed between patients seen in otolaryngologist and APP-led clinics 2) to compare clinical characteristics of patients seen by provider type.Retrospective cohort study at an academic, tertiary care pediatric otolaryngology practice. All children were18 years old and underwent evaluation for RAOM followed by BMT. We compared time in days from scheduling pre-operative appointment to appointment date and time from appointment to BMT between patients seen by APPs and otolaryngologists using Mann-Whitney U tests and multivariate linear regression models. We compared clinical characteristics by provider type using Mann-Whitney U tests and Fisher exact tests.A total of 957 children were included. Children seen by APPs had significantly shorter wait times for appointments (median 19 vs. 39 days, P .001) and shorter times from preoperative appointment to BMT (median 25 vs. 37 days, P .001). Patients seen by otolaryngologists had increased prevalence of craniofacial abnormalities, Down Syndrome, hearing loss, history of otologic surgery, and higher ASA physical status classification.Children seen by APPs received care more quickly than those seen by otolaryngologists. Patients seen by otolaryngologists tended to be more medically complex. Implementation of independent APP clinics may expedite and improve access to BMT for children with RAOM.3 Laryngoscope, 131:2133-2140, 2021.

Objective. To review a literature published over the past 5 years and our own data on the etiology of lower respiratory tract infections (LRTI), antimicrobial resistance and its relationships between sepsis and choice of appropriate antibiotic therapy. Materials and methods. National Nosocomial Infections Surveillance (NNIS) criteria were used to diagnose LRTI. A review of the articles regarding LRTI from the Russian and international English language journals published over 6 years was performed. Identification of microorganisms was performed by culture over the period of 2003-2013;since 2014, MALDI-TOF MS method was used for this purpose. Results. Despite the ongoing policy to limit the use of antimicrobial therapy in the ICUs, there is an increase in carbapenemase-producing isolates in the ICUs from 2.2% (2018) to 11.7% (2020, 9 months). Along with the trend to increase in carbapenemase-producing pathogens causing LRTI, their variability is also increasing. In particular, it applies to strains producing carbapenemases OXA-48 or combination of OXA- 48 with KPC;with the trend to combined production of carbapenemase beginning at 2019. Conclusions. Carbapenemase producers are becoming more widespread in the ICU settings, including the lower respiratory tract in mechanically ventilated patients. Practitioners didn’t get used to associate VAP with the Sepsis-3 criteria. The changes in etiology include the increased rate of carbapenem-resistant Enterobacterales and non-fermenting Gram-negative bacteria, primarily Acinetobacter spp., in Russia. It’s due to improved quality of respiratory support and increased consumption of carbapenems, tigecycline and polymyxins. Significant increase of OXA-48-producing pathogens is likely to be associated with a poor compliance with temporary guidelines on COVID-19 with regard to antibiotic therapy. © 2021, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

In the second decade of the twenty-first century, globalization is responsible for the economic situation in the world. There is a certain trend away from competition between individual transport companies and towards competing supplies and cooperation between companies in order to obtain competitive advantages. Trade cooperation between Belarus and Germany has recently developed quite actively. Bilateral trade is characterized by large volumes of investment imports from Germany, based on the supply of machines, equipment and vehicles. The development of the logistics sector in Belarus has lagged somewhat behind schedule, taking into account modern trends in neighboring countries. The Republic of Belarus and Germany are at very different levels in the logistics sector and have problems of varying degrees. However, there is one important factor that connects the two countries in achieving their goals - professional and human resources, as each component of supply chain management involves people, in one way or another.

In the burn treatment landscape, a variety of skin substitutes, human tissue-sourced products, and other products are being developed based on tissue engineering (ie, the combination of scaffolds, cells, and biologically active molecules into functional tissue with the goal of restoring, maintaining, or improving damaged tissue or whole organs) to provide dermal replacement, prevent infection, or prevent or mitigate scarring. Skin substitutes can have a variety of compositions (cellular vs acellular), origins (human, animal, or synthetically derived), and complexities (dermal or epidermal only vs composite). The regulation of tissue-engineered products in the United States occurs by one of several pathways established by the U.S. Food and Drug Administration, including a Biologics License Application (BLA), a 510(k) (Class I and Class II devices), Premarket Approval (Class III devices), or a human cells, tissues, and cellular and tissue-based products designation. Key differentiators among these regulatory classifications include the amount and type of data required to support a filing. For example, a BLA requires a clinical trial(s) and evaluation of safety and efficacy by the Center for Biologics Evaluation and Research. Applicable approved biological products must also comply with submission of advertising and promotional materials per regulations. This review provides a description of, and associated requirements for, the various regulatory pathways for the approval or clearance of tissue-engineered products. Some of the regulatory challenges for commercialization of such products for the treatment of burns will be explored.

Background Proadrenomedullin (proADM), a vasodilatory peptide with antimicrobial and anti-inflammatory properties, predicts severe outcomes in adults with community-acquired pneumonia (CAP) to a greater degree than C-reactive protein and procalcitonin. We evaluated the ability of proADM to predict disease severity across a range of clinical outcomes in children with suspected CAP. Methods We performed a prospective cohort study of children 3 months to 18 years with CAP in the emergency department. Disease severity was defined as mild (discharged home), mild–moderate (hospitalized but not moderate–severe or severe), moderate–severe (eg, hospitalized with supplemental oxygen, broadening of antibiotics, complicated pneumonia), and severe (eg, vasoactive infusions, chest drainage, severe sepsis). Outcomes were examined using proportional odds logistic regression within the cohort with suspected CAP and in a subset with radiographic CAP. Results Among 369 children, median proADM increased with disease severity (mild: median [IQR], 0.53 [0.43–0.73]; mild–moderate: 0.56 [0.45–0.71]; moderate–severe: 0.61 [0.47–0.77]; severe: 0.70 [0.55–1.04] nmol/L) (P = .002). ProADM was significantly associated with increased odds of developing severe outcomes (suspected CAP: OR, 1.68; 95% CI, 1.2–2.36; radiographic CAP: OR, 2.11; 95% CI, 1.36–3.38) adjusted for age, fever duration, antibiotic use, and pathogen. ProADM had an AUC of 0.64 (95% CI, .56–.72) in those with suspected CAP and an AUC of 0.77 (95% CI, .68–.87) in radiographic CAP. Conclusions ProADM was associated with severe disease and discriminated moderately well children who developed severe disease from those who did not, particularly in radiographic CAP.

Background and objective Many children receiving chemotherapy struggle with therapy-induced side effects. To date, there has been no literature investigating the needs, knowledge, or implementation of osteopathic manipulative treatments (OMT) as a supportive care option in pediatric oncology. We hypothesized that pediatric oncology clinicians, caregivers, and patients have (a) limited knowledge of OMT and (b) dissatisfaction with current supportive care options and (c) would be interested in having OMT available during chemotherapy, once educated. Methods Participants included three cohorts: (1) children aged ≥ 9 years, diagnosed with cancer and actively receiving chemotherapy; (2) their caregivers; and (3) oncology clinicians at Nationwide Children’s Hospital. Participants completed 1:1 semi-structured interviews, which were audio-recorded, transcribed, and analyzed for thematic content regarding their perception of supportive care measures and views on OMT. Quantitative data was summarized descriptively. Results A total of 60 participants completed the interview. Participants demonstrated limited awareness of osteopathic medicine; no participant had more than “some” knowledge of OMT. After education about OMT using a brief video, all clinicians, caregivers, and 95% of patients were receptive to OMT as a supportive care option. Major themes included the following: (a) patients have uncontrolled chemotherapy side effects, (b) improved supportive care options are desired, and (c) osteopathic medicine is a favorable supportive care adjunct. Conclusions Pediatric oncology clinicians, caregivers, and patients reported a need for better management of chemotherapy-associated side effects and an interest in utilizing OMT. These findings support further investigation into the safety, feasibility, and efficacy of implementing OMT in the pediatric oncology clinical setting.

Incidence of Parkinson disease progressively grows with increasing age and percentage of elderly people in the global population. Clear understanding of the causes of dopaminergic neurons death in Substantia nigra and Parkinson disease pathogenesis are currently absent, not speaking of an efficient therapy. However, an early diagnosis of dopaminergic neurons degeneration and prescription of dopamine replacement therapy significantly slow down the rate of symptoms progression. An increased concentration of iron in Substantia nigra of Parkinson disease patients has been shown in several studies. In this review we summarized the data concerning a potential significance of lactoferrin, the iron-binding protein of exocrine secretions and neutrophils, for early diagnosis and treatment of Parkinson disease. Salivary and lacrimal lactoferrin levels in Parkinson disease patients were higher than those observed in the control group. Plasma levels of lactoferrin inversely correlated with Parkinson disease severity even after treatment with Levodopa, a dopamine agonist, and with monoaminooxidase inhibitors. Lactoferrin levels in cerebrospinal fluid of Parkinson disease patients negatively correlated with the tumor necrosis factor-alpha concentration. Lactoferrin treatment of rodents with several experimental models of Parkinson disease (induced by rotenone, MPTP) protected neurons and mitigated the symptoms of neurodegeneration. Some contradictions about the positive effects of lactoferrin as a remedy in Parkinson disease animal models and possible participation of lactoferrin in accumulation of iron in neurons are discussed.

Objective: We previously demonstrated that plasma levels of F-actin and Thymosin Beta 4 differs among patients with septic shock, non-infectious systemic inflammatory syndrome and healthy controls ...

In this article, the authors consider the possibility of using a hybrid energy storage system to even out the load profile of the enterprise. Solving the problem of rational use of energy storage taking into account the initial variable load schedule will significantly reduce not only the cost of electricity consumption by the enterprise, but also the costs of its production. Detailed characteristics of batteries with various types of electrolytes and supercapacitors are given. A model of the active scheme of a hybrid electric energy storage system consisting of a lithium-ion battery and a supercapacitor unit with the corresponding characteristics is presented. The model was carried out by using the SimPowerSystems software in MatLab. During the simulation, the temperature and the aging effects and of the batteries were not taken into account. The selfdischarge parameter of the battery was also not presented. As a result of the simulation, discharge characteristics of supercapacitors and batteries were obtained based upon which the expediency of their combined use for leveling load profiles of various types was substantiated. The paper presents the results of the simulation of operating modes of a hybrid energy storage device, combining the advantages of two types of energy storage devices, as well as a diagram of delivered power to the network, corresponding to the specified parameters. The paper provides a mathematical description of the increasing power by hybrid storage system resulting from the combined use of supercapacitors and batteries. The paper presents the dependence of the power increase ratio on the frequency and the pulse current duty ratio, which proves that the maximum possible output power of the hybrid storage system can be several times greater than the power of a single battery having the same parameters.

Maximizing the flow of students through the science, technology, engineering, and math (STEM) pipeline is important to promoting human capital development and reducing economic inequality1. A critical juncture in the STEM pipeline is the highly-cumulative sequence of secondary school math courses2–5. Students from disadvantaged schools are less likely to complete advanced math courses, but debate continues about why6,7. Here, we address this question using studentpolygenic scores, which are DNA-based indicators of propensity to succeed in education8. We integrated genetic and official school transcript data from over 3,000 European-ancestry students from U.S. high schools. We used polygenic scores as a molecular tracer to understand how the flow of students through the high school math pipeline differs in socioeconomically advantaged versus disadvantaged schools. Students with higher education polygenic scores were tracked to more advanced math already at the beginning of high school and persisted in math for more years. Molecular tracer analyses revealed that the dynamics of the math pipeline differed by school advantage. Compared to disadvantaged schools, advantaged schools tracked more students with high polygenic scores into advanced math classes at the start of high school, and they buffered students with low polygenic scores from dropping out of math. Across all schools, even students with exceptional polygenic scores (top 2%) were unlikely to take the most advanced math classes, suggesting substantial room for improvement in the development of potential STEM talent. These results link new molecular genetic discoveries to a common target of educational-policy reforms.

Importance: Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective: To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants: The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures: Tracheal intubation. Main Outcomes and Measures: The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure 30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation

Calorie restriction (CR) slows aging and increases healthy lifespan in model organisms. We tested if CR slowed biological aging in humans using DNA methylation analysis of blood samples from N=197 participants in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) randomized controlled trial. We quantified CR effects on biological aging by comparing change scores for six epigenetic-clock and Pace-of-Aging measures between n=128 CR-group and n=69 ad-libitum-control-group participants at 12- and 24-month follow-ups. CR effects were strongest for DunedinPACE Pace of Aging (12-month Cohen’s d=0.3; 24-month Cohen’s d=0.2, p0.08). CR effects for other epigenetic clocks were in the opposite direction (all p>0.15). CALERIE intervention slowed Pace of Aging but showed minimal effect on epigenetic clocks hypothesized to reflect longer term accumulation of aging burden.

Purpose Despite continued development of targeted therapies for children with cancer, patients continue to experience an array of unwanted side effects. Children with solid tumors may experience constipation as a result many treatment variables. Our objective was to investigate the prevalence and treatment of constipation in hospitalized children with solid tumors treated with chemotherapy. Methods We retrospectively analyzed data from 48 children’s hospitals in the Pediatric Health Information System, extracting patients 0–21 years of age with a solid tumor diagnosis hospitalized from October 2015-December 2019. Primary study outcome investigated which solid tumor subgroups received the diagnosis of constipation or received the most constipation medications while receiving chemotherapy for a cancer diagnosis. Results We identified 13,375 unique patients with a solid tumor diagnosis receiving chemotherapy. Constipation was the most common gastrointestinal complaint with 8,658 (64.7%; 95% Cl: 63.9–65.5%) meeting our defined constipation diagnosis. Bone cancers had the highest percentage (69.9%) of patients with constipation, while Hodgkin’s lymphoma had the lowest, though 52.1% of patients were affected. A total of 44% (n = 35,301) of encounters received an opioid at some point during admission. Of patients receiving constipation medications, the most commonly prescribed was poly-ethyl glycol (n = 25,175, 31.7%), followed by docusate (n = 11,297, 14.2%), senna (n = 10,325, 13.0%), and lactulose (n = 5,501, 6.9%). Conclusions Constipation is the most common gastrointestinal issue that children with solid tumors experience while receiving chemotherapy. Increased attention should be given to constipation prophylaxis and treatment in children with solid tumors undergoing chemotherapy.

Background:Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously, we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al., 2020). Here, we report a next-generation DNA-methylation biomarker of Pace of Aging, DunedinPACE (for Pace of Aging Calculated from the Epigenome).Methods:We used data from the Dunedin Study 1972–1973 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named DunedinPACE, in five additional datasets.Results:DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of incident morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge.Conclusions:DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience.Funding:This research was supported by US-National Institute on Aging grants AG032282, AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1.

Vasopressors are ubiquitous in intensive care units. While central venous catheters are the preferred route of infusion, recent evidence suggests peripheral administration may be safe for short, single-agent courses. Here, we identify risk factors and develop a predictive model for patient central venous catheter requirement using the Medical Information Mart for Intensive Care, a single-centre dataset of patients admitted to an intensive care unit between 2008 and 2019. Using prior literature, a composite endpoint of prolonged single-agent courses (>24 hours) or multi-agent courses of any duration was used to identify likely central venous catheter requirement. From a cohort of 69,619 intensive care unit stays, there were 17,053 vasopressor courses involving one or more vasopressors that met study inclusion criteria. In total, 3807 (22.3%) vasopressor courses involved a single vasopressor for less than six hours, 7952 (46.6%) courses for less than 24 hours and 5757 (33.8%) involved multiple vasopressors of any duration. Of these, 3047 (80.0%) less than six-hour and 6423 (80.8%) less than 24-hour single vasopressor courses used a central venous catheter. Logistic regression models identified associations between the composite endpoint and intubation (odds ratio (OR) 2.36, 95% confidence intervals (CI) 2.16 to 2.58), cardiac diagnosis (OR 0.72, CI 0.65 to 0.80), renal impairment (OR 1.61, CI 1.50 to 1.74), older age (OR 1.002, Cl 1.000 to 1.005) and vital signs in the hour before initiation (heart rate, OR 1.006, CI 1.003 to 1.009; oxygen saturation, OR 0.996, CI 0.993 to 0.999). A logistic regression model predicting the composite endpoint had an area under the receiver operating characteristic curve (standard deviation) of 0.747 (0.013) and an accuracy of 0.691 (0.012). This retrospective study reveals a high prevalence of short vasopressor courses in intensive care unit settings, a majority of which were administered using central venous catheters. We identify several important risk factors that may help guide clinicians deciding between peripheral and central venous catheter administration, and present a predictive model that may inform future prospective trials.

BACKGROUND Childrenwith acute lymphoblastic leukemia (ALL) suffer a litany of chemotherapy-induced side effects. Constipation secondary to vinca alkaloids, psychological stressors, and opioid use are common issues for children newly diagnosed with leukemia. This study investigated the morbidity associated with constipation including infections, mucositis, and healthcare utilization in hospitalized children with ALL receiving induction chemotherapy. METHODS We analyzed data from 48 children's hospitals in the Pediatric Health Information System, extracting patients 1-21 years of age with ALL, hospitalized for induction from October 2015 through December 2019. Data were analyzed using nonparametric statistics, and comparisons of outcomes between those with and without constipation were presented as adjusted odds ratios (aOR). RESULTS We identified 2586 (56%) patients with constipation out of a total of 4622 unique ALL patients in induction. Compared to patients without constipation during induction, patients with constipation were significantly more likely to have mucositis (aOR = 2.30; p = 0.0010), perirectal issues (aOR = 3.21; p = 0.0092), or abdominal radiograph exposure (aOR = 2.40; p < 0.0001). The median length of induction hospitalization was significantly greater in those with constipation compared to those without constipation (10 days vs. 8 days; p < 0.0001). CONCLUSIONS Children with ALL suffering from constipation during induction therapy have increased length of stay, mucositis, imaging, and overall healthcare utilization compared to children without constipation. Further research should explore the causative relationship between constipation and infections. Increased attention should be given to constipation management in patients with ALL at the start of induction therapy, particularly in patients with complications or prolonged hospitalizations.

BackgroundUrine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis.ResultsOf the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient—oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged—oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent—oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19–1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97–1.34], p = 0.103).ConclusionsOliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome., 0, info:eu-repo/semantics/published

Objective: Post-tracheotomy swallowing function has not been well described in the pediatric population. This study aims to (1) determine differences in swallowing functioning pre- and post-tracheotomy and (2) examine the association between postoperative dysphagia and indication for tracheotomy, age at the time of tracheotomy, and time between tracheotomy and modified barium swallow (MBS). Methods: A retrospective chart review was performed on 752 patients who underwent a tracheotomy from 2003 to 2018 and had adequate documentation for review. Patients were included if they received a post-operative MBS. Descriptive statistics, logistic regression, and Fisher’s exact test were used to analyze the data. Results: The cohort included 233 patients. The mean age at the time of tracheotomy was 25 months (±50.5). The indications for the tracheotomy were upper airway obstruction (110/233, 47.2%), chronic respiratory failure (104/233, 44.6%), and neurologic disease (19/233, 8.2%). The mean time from tracheotomy to post-operative MBS was 224 days (±297.7). Of the patients who had documented pre- and post-tracheotomy diets, nearly half of patients had improvement in their swallowing function after tracheotomy placement (82/195; 42.1%). Post-tracheotomy MBS recommended thickened liquids in 30.9% of the patients (72/233) and 42.5% (99/233) were recommended thin liquids. The remainder (62/233, 26.6%) remained nothing by mouth (NPO). Patients with neurological disease as the indication for the tracheotomy were more likely to remain NPO ( P = .039). Conclusion: A tracheotomy can functionally and anatomically affect swallowing in pediatric patients. The majority of our studied cohort was able to resume some form of an oral diet postoperatively based on MBS. This study highlights the need for objective measurements of swallowing in the postoperative tracheotomy patient to allow for safe and timely commencement of an oral diet. Level of Evidence Level 3.

ImportanceExposure to socioeconomic disadvantage is associated with rapid cognitive aging. Biological aging, the progressive loss of system integrity that occurs as we age is proposed as a modifiable process mediating this health inequality.ObjectiveTo test the hypothesis that socioeconomic disparities in cognitive aging in older adults is explained by accelerated biological aging.DesignObservational cohort study.SettingU.S. Health and Retirement Study DNA-methylation sub-study.ParticipantsN=3,648 (49% male) adults aged 50-100 (M=70, SD=10) with DNA methylation data.ExposuresSocioeconomic status (SES) was measured from years of education and household wealth. The extent and pace of biological aging were quantified using three DNA-methylation measures: PhenoAge, GrimAge, and DunedinPoAm.Main Outcomes and MeasuresCognitive aging was measured from repeated longitudinal assessments of immediate and delayed word recall. Latent growth curve modeling estimated participants’ level of memory performance and rate of decline over 2-11 follow-up assessments spanning 2-20 years. Models were estimated to assess whether the relationship between SES and memory trajectories was mediated by biological aging.ResultsOlder adults with lower SES had lower memory performance, faster decline and exhibited accelerated biological aging (SES β=.33, 99% CI[.30-.36], biological-aging measure effect size associations ranged from .08 to .20). Accelerated biological aging was associated with decreased memory performance and faster memory decline (effect-size range .03 to .18). Higher SES was associated with slower biological aging for White and Black men and women, but not Latinx participants. The relationship between biological aging measures and memory was weaker for Black and Latinx participants compared with White people. In mediation analysis, biological aging accounted for 3-9% of the SES-memory gradient in White participants. There was no evidence of mediation in Black or Latinx participants.Conclusions and RelevanceAmong a national sample of older adults, DNA-methylation measures of biological aging were associated with memory trajectories in White, but not Black or Latinx older adults. These results challenge the assumption that DNA-methylation biomarkers of aging that were developed in primarily White people can quantify aging processes affecting cognition in Black and Latinx older adults.

BACKGROUND AND OBJECTIVES: Children who grow up in socioeconomic disadvantage face increased burden of disease and disability throughout their lives. One hypothesized mechanism for this increased burden is that early-life disadvantage accelerates biological processes of aging, increasing vulnerability to subsequent disease. To evaluate this hypothesis and the potential impact of preventive interventions, measures are needed that can quantify early acceleration of biological aging in childhood. METHODS: Saliva DNA methylation and socioeconomic circumstances were measured in N = 600 children and adolescents aged 8 to 18 years (48% female) participating in the Texas Twin Project. We measured pace of biological aging using the DunedinPoAm DNA methylation algorithm, developed to quantify the pace-of-aging–related decline in system integrity. We tested if children in more disadvantaged families and neighborhoods exhibited a faster pace of aging as compared with children in more affluent contexts. RESULTS: Children living in more disadvantaged families and neighborhoods exhibited a faster DunedinPoAm-measured pace of aging (r = 0.18; P = .001 for both). Latinx-identifying children exhibited a faster DunedinPoAm-measured pace of aging compared with both White- and Latinx White–identifying children, consistent with higher levels of disadvantage in this group. Children with more advanced pubertal development, higher BMI, and more tobacco exposure exhibited faster a faster DunedinPoAm-measured pace of aging. However, DunedinPoAm-measured pace of aging associations with socioeconomic disadvantage were robust to control for these factors. CONCLUSIONS: Children growing up under conditions of socioeconomic disadvantage exhibit a faster pace of biological aging. DNA methylation pace of aging might be useful as a surrogate end point in evaluation of programs and policies to address the childhood social determinants of lifelong health disparities.

OBJECTIVE. Although neck impairment has been described following surgical resection, limited studies have investigated its prevalence in nonsurgical treatment. The purpose of this study is to determine the prevalence and predictors of neck disability following head and neck cancer (HNC) treatment and to explore its association with quality of life (QOL). STUDY DESIGN. Cross-sectional study. SETTING. HNC survivorship clinic. SUBJECTS AND METHODS. We identified 214 survivors who completed treatment ≥1 year prior to evaluation in the clinic. Self-reported neck impairment was measured using the Neck Disability Index. QOL was measured using the University of Washington QOL Questionnaire, with physical and social subscale scores calculated. Regression analysis and trend tests were employed to explore associations. RESULTS. Over half of survivors (54.2%) reported neck disability. The odds of neck disability in survivors who received nonsurgical treatment and those who received surgery plus adjuvant treatment were 3.46 and 4.98 times higher compared to surgery alone (P = .008, P = .004). Survivors who underwent surgery only had higher physical and social QOL than those who received nonsurgical treatment (physical QOL: P < .001, social QOL: P = .023) and those who received surgery plus adjuvant treatment (physical QOL: P

The article discusses the experience of operating a wind power complex with a low-power wind power installa- tion (5 kW), the use of which is promising for powering remote oil production facilities, exploration and other types of mining operations. The structure of the studied complex and its characteristics, technical problems that have arisen during operation for 6 years are given. The elements of the wind energy complex – the battery charge regulator and the inverter-converter are considered. The consequences of the mechanical regulator failure of battery charge are con- sidered and recommendations for its replacement are presented. The issues of diagnostics and repair of one of the main elements of the complex – the inverter-converter, its component – DC link are highlighted in detail. Oscil- lograms of the output voltage of the inverter-converter are presented for different capacities of the DC link and the images of the repaired inverter-converter are given. Recommendations are given on choosing an inverter-converter and setting up the operating modes of the wind energycomplex .

Favorable histology (FH) Wilms tumor (WT) is one of the most curable of all human cancers, yet a small minority of patients fail treatment. The underlying biological pathways that lead to therapy resistance are unknown. We report a case of initially unresectable, FH WT which revealed limited necrosis and persistent blastemal predominant histology following neoadjuvant chemotherapy. Despite intensification of therapy and whole abdominal radiation, the patient relapsed and succumbed to her disease. In an effort to discover candidate drivers of drug resistance, whole exome sequencing and copy number analysis were performed on samples from all 3 tumor specimens. Sequencing results revealed outgrowth of clones with a dramatically different genetic landscape including dominant mutations that could explain therapy evasion, some of which have not been previously reported in WT. Our results implicate PPM1D, previously shown to be associated with drug resistance in other tumors, as the major driver of treatment failure.

Observational data have shown that some cancer survivors develop chronic conditions like frailty, sarcopenia, cardiac dysfunction, and mild cognitive impairment earlier and/or at a greater burden than similarly aged individuals never diagnosed with cancer or exposed to systemic or targeted cancer therapies. In aggregate, cancer- and treatment-related physical, cognitive, and psychosocial late- and long-term morbidities experienced by cancer survivors are hypothesized to represent accelerated or accentuated aging trajectories. However, conceptual, measurement, and methodological challenges have constrained efforts to identify, predict, and mitigate aging-related consequences of cancer and cancer treatment. In July 2018, the National Cancer Institute convened basic, clinical, and translational science experts for a think tank titled “Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors.” Through the resulting deliberations, several research and resource needs were identified, including longitudinal studies to examine aging trajectories that include detailed data from before, during, and after cancer treatment; mechanistic studies to elucidate the pathways that lead to the emergence of aging phenotypes in cancer survivors; long-term clinical surveillance to monitor survivors for late-emerging effects; and tools to integrate multiple data sources to inform understanding of how cancer and its therapies contribute to the aging process. Addressing these needs will help expand the evidence base and inform strategies to optimize healthy aging of cancer survivors.

Objectives Chest radiographs (CXRs) are often performed in children with respiratory illness to inform the decision to prescribe antibiotics. Our objective was to determine the factors associated with clinicians' plans to treat with antibiotics prior to knowledge of CXR results and the associations between preradiograph plans with antibiotic prescription and return to medical care. Methods Previously healthy children aged 3 months to 18 years with a CXR for suspected pneumonia were enrolled in a prospective cohort study in the emergency department. Our primary outcomes were antibiotic prescription or administration in the emergency department and medical care sought within 7 to 15 days after discharge. Inverse probability treatment weighting was used to limit bias due to treatment selection. Inverse probability treatment weighting was included in a logistic regression model estimating the association between the intention to give antibiotics and outcomes. Results Providers planned to prescribe antibiotics prior to CXR in 68 children (34.9%). There was no difference in the presence of radiographic pneumonia between those with and without a plan for antibiotics. Children who had a plan for antibiotics were more likely to receive antibiotics than those without (odds ratio [OR], 6.39; 95% confidence interval [CI], 3.7-11.0). This association was stronger than the association between radiographic pneumonia and antibiotic receipt (OR, 3.49; 95% CI, 1.98-6.14). Children prescribed antibiotics were more likely to seek care after discharge than children who were not (OR, 1.85; 95% CI, 1.13-3.05). Conclusions Intention to prescribe antibiotics based on clinical impression was the strongest predictor of antibiotic prescription in our study. Prescribing antibiotics may lead to subsequent medical care after controlling for radiographic pneumonia.

Purpose: To investigate age-related differences in outcomes of critically ill patients with sepsis around the world., Methods: We performed a secondary analysis of data from the prospective ICON audit, in which all adult ( >16 years ) patients admitted to participating ICUs between May 8 and 18, 2012, were included, except admissions for routine postoperative observation. For this sub-analysis, the 10,012 patients with completed age data were included. They were divided into five age groups - 80 years. Sepsis was defined as infection plus at least one organ failure., Results: A total of 2963 patients had sepsis, with similar proportions across the age groups (80 = 30.9%). Hospital mortality increased with age and in patients >80 years was almost twice that of patients 70 years was independently associated with increased risk of dying., Conclusions: The odds for death in ICU patients with sepsis increased with age with the maximal rate of increase occurring between the ages of 71 and 77 years. (C) 2019 Elsevier Inc. 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Amisi] Clin Univ Kinshasa, Kinshasa, DEM REP CONGO., [Charra, B.] Chu Ibn Rochd Casablanca, Casablanca, Morocco., [Faroudy, M.] Ibn Sina Hosp, Rabat, Morocco., [Doedens, L.] Chris Hani Baragwanath Acad Hosp, Soweto, South Africa., [Farina, Z.] Grays Hosp, Pietermaritzburg, South Africa., [Adler, D.] Sandton Medi Clin, Sandton, South Africa., [Balkema, C.] Tygerberg Hosp, Cape Town, South Africa., [Kok, A.] Union Hosp Alberton, Alberton, South Africa., [Alaya, S.] Bizerte Hosp, Bizerte, Tunisia., [Gharsallah, H.] Mil Hosp Tunis, Tunis, Tunisia., [Muzha, D.] Natl Trauma Ctr & Mil Hosp, Tirana, Albania., [Temelkov, A.] Alexandrovska Univ Hosp, Sofia, Bulgaria., [Georgiev, G.] Emergency Univ Hosp Pirogov, Sofia, Bulgaria., [Simeonov, G.] Tokuda Hosp Sofia, Sofia, Bulgaria., [Tsaryanski, G.] Uh St Ekaterina Sofia, Sofia, Bulgaria., [Georgiev, S.] Univ Hosp Obstet & Gynaecol, Sofia, Bulgaria., [Seliman, A.] Univ Hosp Sveta Marina Varna, Varna, Bulgaria., [Vrankovic, S.] Gen Hosp Siben, Shibenik, Croatia., [Vucicevic, Z.] Univ Hosp Ctr Sestre Milosrdnice, Zagreb, Croatia., [Gornik, I] Univ Hosp Ctr Zagreb, Zagreb, Croatia., [Barsic, B.] Univ Hosp Infect Dis, Zagreb, Croatia., [Husedzinovic, I] Univ Hosp Dubrava, Zagreb, Croatia., [Pavlik, P.] Ctr Cardiovasc & Transplant Surg, Prague, Czech Republic., [Manak, J.] Charles Univ Hosp, Prague, Czech Republic., [Kieslichova, E.] IKEM, Prague, Czech Republic., [Turek, R.] KNTB Zlin AS, Prague, Czech Republic., [Fischer, M.] Krajska Nemocnice Liberec, Prague, Czech Republic., [Valkova, R.] Masarykova Nemocnice V Usti Labem, Labem, Czech Republic., [Dadak, L.] St Annes Univ Hosp Brno, Brno, Czech Republic., [Dostal, P.] Univ Hosp Haradec Kralove, Haradec Kralove, Czech Republic., [Malaska, J.] Univ Hosp Brno, Brno, Czech Republic., [Hajek, R.] Univ Hosp Olomouc, Olomouc, Czech Republic., [Zidkova, A.] Univ Hosp Plzen, Plzen, Czech Republic., [Lavicka, P.] Charles Univ Hosp Plzen, Plzen, Czech Republic., [Starkopf, J.] Tartu Univ Hosp, Tartu, Estonia., [Kheladze, Z.] Crit Care Med Inst, Gainesville, Georgia., [Chkhaidze, M.] Jo Ann Med Ctr, Tbilisi, Georgia., [Kaloiani, V] Kipshidze Cent Univ Hosp, Tbilisi, Georgia., [Medve, L.] Dr Kenessey Albert Hosp, Balassagyarmat, Hungary., [Sarkany, A.] Fejer Cty St George Teaching Hosp, Szekesfehervar, Hungary., [Kremer, I] Flor Ferenc Cty Hosp, Budapest, Hungary., [Marjanek, Z.] Javorszky Odon Hosp, Vac, Hungary., [Tamasi, P.] Peterfy Hosp Budapest, Budapest, Hungary., [Krupnova, I] Infectol Ctr Latvia, Riga, Latvia., [Vanags, I] Paul Stradins Clin Univ Hosp, Riga, Latvia., [Liguts, V] Riga East Clin Univ Hosp, Riga, Latvia., [Pilvinis, V] Hosp Lithuanian Univ Hlth Sci Kauno Klinikos, Kaunas, Lithuania., [Vosylius, S.] Vilnius Univ Hosp, Vilnius, Lithuania., [Kekstas, G.] HSICU, Vilnius Univ Hosp Santariskiu Clin, Vilnius, Lithuania., [Balciunas, M.] CICU, Vilnius Univ Hosp Santariskiu Clin, Vilnius, Lithuania., [Kolbusz, A.] Csk Mswia, Warsaw, Poland., [Kubler, A.] Med Univ, Wroclaw, Poland., [Mielczarek, B.] Med Univ Wroclaw, Wroclaw, Poland., [Mikaszewska-Sokolewicz, M.] Med Univ Warsaw, Warsaw, Poland., [Kotfis, K.] Pomeranian Med Univ, Szczecin, Poland., [Tamowicz, B.] Reg Hosp Poznan, Poznan, Poland., [Sulkowski, W.] Szpital Powiatowy W Ostrowi Mazowieckiej, Ostrow Mazowiecka, Poland., [Smuszkiewicz, P.] Univ Hosp, Poznan, Poland., [Pihowicz, A.] Wojewodzki Szpital Zakazny, Torun, Poland., [Trejnowska, E.] Wojewodzkie Ctr Med, Warsaw, Poland., [Hagau, N.] Emergency Cty Hosp Cluj, Cluj Napoca, Romania., [Filipescu, D.] Emergency Inst Cardiovasc Dis, Bucharest, Romania., [Droc, G.] Fundeni Clin Inst, Bucharest, Romania., [Lupu, M.] Galati Hosp, Bucharest, Romania., [Nica, A.] Lnbi Prof Dr Matei Bals, Bucharest, Romania., [Stoica, R.] Inst Pulmonol Marius Nasta, Bucharest, Romania., [Tomescu, D.] Inst Clin Fundeni, Bucharest, Romania., [Constantinescu, D.] Sfantul Pantelimon Hosp, Bucharest, Romania., [Zbaganu, G. Valcoreanu] Spitalul Cf 2 Bucuresti, Bucharest, Romania., [Slavcovici, A.] Iuliu Hatieganu Univ Med & Pharm, Teaching Hosp Infect Dis, Cluj Napoca, Romania., [Bagin, V] City Clin Hosp 40, St Petersburg, Russia., [Belsky, D.] City Hosp 40, St Petersburg, Russia., [Palyutin, S.] Clin Hosp NVNV Solovyev, Yaroslavl, Russia., [Shlyapnikov, S.] Emergency Res Inst NA Djanelidze, St Petersburg, Russia., [Bikkulova, D.] Fed Res Ctr Paediat Haematol Oncol & Immunol, Moscow, Russia., [Gritsan, A.] Krasnoyarsk State Med Univ, Krasnoyarsk Reg Hosp, Krasnoyarsk, Russia., [Natalia, G.] Med Assoc Novaya Bolnitsa, Ekaterinburg, Russia., [Makarenko, E.] Mil Med Acad, Ekaterinburg, Russia., [Kokhno, V] Novosibirsk Med Univ, Novosibirsk, Russia., [Tolkach, A.] Omsk Reg Clin Hosp, Omsk, Russia., [Kokarev, E.] Railway Hosp Khabarovsk, Khabarovsk, Russia., [Belotserkovskiy, B.] St Alexy Hosp, St Louis, France., [Zolotukhin, K.] State Dist Hosp, Moscow, Russia., [Kulabukhov, V] Vishnevsky Inst Surg, Moscow, Russia., [Soskic, L.] Clin Ctr Serbia, Clin Cardiac Surg, Belgrade, Serbia., [Palibrk, I] Clin Ctr Serbia, Clin Digest Surg, Belgrade, Serbia., [Jankovic, R.; Jovanovic, B.] Clin Ctr Nis, Clin Vasc Surg, Nish, Serbia., [Pandurovic, M.] Clin Ctr Serbia, Emergency Ctr, Belgrade, Serbia., [Bumbasirevic, V] Clin Ctr Belgrade, Emergency Ctr, Belgrade, Serbia., [Uljarevic, B.] Gen Univ Hosp, Belgrade, Serbia., [Surbatovic, M.] Mil Med Acad, Belgrade, Serbia., [Ladjevic, N.] Urol Hosp, Belgrade, Serbia., [Slobodianiuk, G.] Dist Hosp, Bratislava, Slovakia., [Sobona, V] Fac Hosp, Bratislava, Slovakia., [Cikova, A.] Univ Hosp Bratislava, Hosp Ruzinov ICU, Bratislava, Slovakia., [Gebhardtova, A.] Univ Hosp Ruzinov Bratislava, Bratislava, Slovakia., [Jun, C.] Qingdao Univ, Tertiary Hosp, Qingdao, Shandong, Peoples R China., [Yunbo, S.] Qingdao Univ, Affiliated Hosp, Med Coll, Qingdao, Shandong, Peoples R China., [Dong, U.] Beijing Canc Hosp, Beijing Inst Canc Res, Beijing, Peoples R China., [Feng, S.] Beijing Chaoyang Hosp, Beijing, Peoples R China., [Duan, M.] Beijing Friendship Hosp, Beijing, Peoples R China., [Xu, Y.] Capital Med Univ, Beijing Tongren Hosp, Beijing, Peoples R China., [Xue, X.] Beijing Univ Peoples Hosp, Beijing, Peoples R China., [Gao, T.] Beijing Luhe Hosp, Beijing, Peoples R China., [Xing, X.] Chinese Acad Med Sci, Canc Hosp, Beijing, Peoples R China., [Zhao, X.] China Acad Chinese Med Sci, Guang An Men Hosp, Beijing, Peoples R China., [Li, C.] Peoples Hosp, Chuxiong, Yunnan, Peoples R China., [Gengxihua, G.] Donge Cty Peoples Hosp Shandong Prov, Liaocheng, Shandong, Peoples R China., [Tan, H.] Chinese Acad Med Sci, Fu Wai Hosp, Beijing, Peoples R China., [Xu, J.] Fujian Prov Hosp, Fuzhou, Fujian, Peoples R China., [Jiang, L.] Capital Med Univ, Fuxing Hosp, Beijing, Peoples R China., [Tiehe, Q.] Guangdong Gen Hosp, Guangzhou, Guangdong, Peoples R China., [Bingyu, Q.] Henan Prov Peoples Hosp, Zhengzhou, Henan, Peoples R China., [Shi, Q.] Xi An Jiao Tong Univ, Coll Med, Xian, Shaanxi, Peoples R China., [Lv, Z.] Kunming Third Peoples Hosp, Kunming, Yunnan, Peoples R China., [Zhang, L.] Lanzhou Univ, Hosp 2, Lanzhou, Gansu, Peoples R China., [Jingtao, L.] 309th Hosp, Beijing, Peoples R China., [Zhen, Z.] China Med Univ, Hosp 1, Beijing, Peoples R China., [Wang, Z.] Peking Univ, Shougang Hosp, Beijing, Peoples R China., [Wang, T.] Peking Univ, Hosp 3, Beijing, Peoples R China., [Yuhong, L.] Pla Navy Gen Hosp, Beijing, Peoples R China., [Zhai, Q.] Shandong Univ, Qilu Hosp, Jinan, Shandong, Peoples R China., [Chen, Y.] Jiaotong Univ, Affiliated Med Sch, Ruijin Hosp, Shanghai, Peoples R China., [Wang, C.] Shandong Prov Hosp, Jinan, Shandong, Peoples R China., [Jiang, W.] Shanghai 10th Peoples Hosp, Shanghai, Peoples R China., [Ruilan, W.] Shanghai First Peoples Hosp, Shanghai, Peoples R China., [Chen, Y.; Xiaobo, H.] Sichuan Prov Peoples Hosp, Chengdu, Sichuan, Peoples R China., [Ge, H.] Sir Run Run Shaw Hosp, Hangzhou, Zhejiang, Peoples R China., [Yan, T.] Affiliated Guiyang Med Coll, Guiyang, Guizhou, Peoples R China., [Yuhui, C.] Fudan Univ, Peoples Hosp Shanghai 5, Shanghai, Peoples R China., [Zhang, J.] Dalian Med Univ, Affiliated Hosp 1, Dalian, Peoples R China., [Jian-Hong, F.] Suzhou Univ, Affiliated Hosp 1, Suzhou, Peoples R China., [Zhu, H.] Xinjiang Med Univ, Affiliated Hosp 1, Urumqi, Peoples R China., [Huo, F.; Wang, Y.] Jilin Univ, Hosp 1, Changchun, Jilin, Peoples R China., [Li, C.] First Peoples Hosp Kunming, Kunming, Yunnan, Peoples R China., [Zhuang, M.] Gen Hosp Shenyang Mil Reg, Shenyang, Liaoning, Peoples R China., [Ma, Z.] Peoples Hosp Cangzhou, Cangzhou, Peoples R China., [Sun, J.] Jilin Univ, Hosp 2, Changchun, Jilin, Peoples R China., [Liuqingyue, L.] Second Peoples Hosp Liaocheng City Shandong Prov, Liaocheng, Shandong, Peoples R China., [Yang, M.] Third Xiangya Hosp, Changsha, Hunan, Peoples R China., [Meng, J.] Tongde Hosp Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China., [Ma, S.] Tongji Univ, Shanghai East Hosp, Shanghai, Peoples R China., [Kang, Y.] West China Hosp, Scu, Peoples R China., [Yu, L.] Wuhan Ctr Hosp, Wuhan, Hubei, Peoples R China., [Peng, Q.] Xiangya Hosp, Changsha, Hunan, Peoples R China., [Wei, Y.] Yantai Yuhuangding Hosp, Yantai, Peoples R China., [Zhang, W.] Yantaishan Hosp, Yantai, Shandong, Peoples R China., [Sun, R.] Zhejiang Prov Peoples Hosp, Hangzhou, Zhejiang, Peoples R China., [Yeung, A.] Pamela Youde Nethersole Eastern Hosp, Hong Kong, Peoples R China., [Wan, W.] Princess Margaret Hosp, Hong Kong, Peoples R China., [Sin, K.] Queen Elizabeth Hosp, Hong Kong, Peoples R China., [Lee, K.] United Christian Hosp Hong Kong SAR, Hong Kong, Peoples R China., [Wijanti, M.] Anestesi, Yogyakarta, Indonesia., [Widodo, U.] Pku Muhammadiyah Bantu, Yogyakarta, Indonesia., [Samsirun, H.] Rd Mattaher Hosp Jambi, Jambi City, Indonesia., [Sugiman, T.] Rumah Sakit Pantai Lndah Kapuk, North Jakarta, Indonesia., [Wisudarti, C.] Sardjito Hosp, Yogyakarta, Indonesia., [Maskoen, T.] Sch Med Unpad, Hasan Sadikin Hosp, Bandung, Indonesia., [Hata, N.] Nippon Med Sch, Chiba Hokusoh Hosp, Inzai, Japan., [Kobe, Y.] Chiba Univ Hosp, Chiba, Japan., [Nishida, O.] Fujita Hlth Univ, Sch Med, Toyoake, Aichi, Japan., [Miyazaki, D.] Japanese Red Cross Maebashi Hosp, Maebashi, Gumma, Japan., [Nunomiya, S.] Jichi Med Univ Hosp, Shimotsuke, Japan., [Uchino, S.] Jikei Univ, Sch Med, Tokyo, Japan., [Kitamura, N.] Kimitsu Chuo Hosp, Kisarazu, Japan., [Yamashita, K.] Kochi Med Sch, Nankoku, Kochi, Japan., [Hashimoto, S.] Kyoto Prefectural Univ Med, Kyoto, Japan., [Fukushima, H.] Nara Med Univ Hosp, Kashihara, Nara, Japan., [Adib, N. Nik] Hosp Sultanah Nur Zahirah, Kuala Terengganu, Terengganu, Malaysia., [Tai, L.] Kuala Lumpur Hosp, Kuala Lumpur, Malaysia., [Tony, B.] Queen Elizabeth Hosp 2, Kota Kinabalu, Malaysia., [Bigornia, R.] Cebu Velez Gen Hosp, Cebu, Philippines., [Bigornia, R.] Perpetual Succour Hosp, Cebu, Philippines., [Palo, J.] Med City, Pasig, Philippines., [Chatterjee, S.] Alexandra Hosp, Singapore, Singapore., [Tan, B.] Natl Univ Hlth Syst, Singapore, Singapore., [Kong, A.] Singapore Gen Hosp, Singapore, Singapore., [Goh, S.] Tan Tock Seng Hosp, Singapore, Singapore., [Lee, C.] Natl Taiwan Univ Hosp, Taipei, Taiwan., [Pothirat, C.] Chiaingmai Univ, Maharaj Nakorn Chiangmai Hosp, Chiang Mai, Thailand., [Khwannimit, B.] Prince Songkla Univ, Hat Yai, Thailand., [Theerawit, P.] Ramathibodi Hosp, Bangkok, Thailand., [Pornsuriyasak, P.] Ramathibodi Hosp, Somdech Phra Debaratana Med Ctr, Bangkok, Thailand., [Piriyapatsom, A.] Mahidol Univ, Siriraj Hosp, Bangkok, Thailand., [Mukhtar, A.] Cairo Univ, Giza, Egypt., [Dsicu] Demerdash Surg Intens Care Unit, Cairo, Egypt., [Hamdy, A. Nabil] Ain Shams Fac Med, Cairo, Egypt., [Hosny, H.] Zaitoun Specialized Hosp, Cairo, Egypt., [Ashraf, A.] Gums, Tehran, Iran., [Mokhtari, M.] Sbums, Imam Hossein Hosp, Tehran, Iran., [Nowruzinia, S.] Imamreza Hosp, Mashhad, Razavi Khorasan, Iran., [Lotfi, A.] Laleh Hosp, Tehran, Iran., [Zand, F.] Shiraz Anesthesiol & Crit Care Res Ctr, Shiraz, Iran., [Nikandish, R.] Shiraz Univ Med Sci, Shiraz, Iran., [Moghaddam, O. Moradi] Tehran Med Sci Univ, Tehran, Iran., [Cohen, J.] Rabin Med Ctr, Petah Tiqwa, Israel., [Sold, O.] Sourasky Tel Aviv Med Ctr, Tel Aviv, Israel., [Sfeir, T.] Ctr Hosp Nord, Ettelbruck, Luxembourg., [Hasan, A.] Sohar Hosp, Sohar, Oman., [Abugaber, D.] Specialized Arab Hosp, Nablus, Palestine., [Ahmad, H.] Almana Gen Hosp, Khobar, Saudi Arabia., [Tantawy, T.] KFSHRC, Riyadh, Saudi Arabia., [Baharoom, S.] King Abdulaziz Med City Riyadh, Riyadh, Saudi Arabia., [Algethamy, H.] King Abdulaziz Univ, Jeddah, Saudi Arabia., [Amr, A.] King Saud Med City, Riyadh, Saudi Arabia., [Almekhlafi, G.] Riyadh Mil Hosp, Riyadh, Saudi Arabia., [Coskun, R.] Erciyes Univ, Med Fac, Kayseri, Turkey., [Sungur, M.] Erciyes Univ, Med Sch, Kayseri, Turkey., [Cosar, A.] Gulhane Mil Med Acad, Ankara, Turkey., [Gucyetmez, B.] Int Hosp, Istanbul, Turkey., [Demirkiran, O.] Istanbul Univ, Cerrahpasa Med Sch Hosp, Istanbul, Turkey., [Senturk, E.] Istanbul Univ, Istanbul Med Fac, Istanbul, Turkey., [Ulusoy, H.] Karadeniz Tech Univ, Med Fac, Trabzon, Turkey., [Atalan, H.] Mem Atasehir Hosp, Istanbul, Turkey., [Serin, S.] Pamukkale Univ, Denizli, Turkey., [Kati, I] Yuzuncu Yil Univ, Med Fac, Van, Turkey., [Alnassrawi, Z.] Dubai Hosp, Dubai, U Arab Emirates., [Almemari, A.] Mafraq Hosp, Abu Dhabi, U Arab Emirates., [Krishnareddy, K.] Sheikh Khalifa Med City, Abu Dhabi, U Arab Emirates., [Kashef, S.] Tawam Hosp, Al Ain, U Arab Emirates., [Alsabbah, A.] City Hosp, Dubai, U Arab Emirates., [Poirier, G.] Hop Charles Lemoyne, Longueuil, PQ, Canada., [Marshall, J.] St Michaels Hosp, Toronto, ON, Canada., [Herridge, M.] Toronto Gen Hosp, Toronto, ON, Canada., [Herridge, M.] Toronto Western Hosp, Toronto, ON, Canada., [Fernandez-Medero, R.] San Juan Hosp, San Juan, PR USA., [Fulda, G.] Christiana Care Hlth Syst, Newark, DE USA., [Banschbach, S.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA., [Quintero, J.] El Camino Hosp, Mountain View, CA USA., [Schroeder, E.] George Washington Hosp, Washington, DC USA., [Sicoutris, C.] Hosp Univ Penn, Philadelphia, PA 19104 USA., [Gueret, R.] John H Stroger Hosp Cook Cty, Chicago, IL USA., [Kashyap, R.] Mayo Clin, CCM, Rochester, MN USA., [Bauer, P.] Mayo Clin, PCC, Rochester, MN USA., [Nanchal, R.] Med Coll Wisconsin, Milwaukee, WI 53226 USA., [Wunderink, R.] Northwestern Mem Hosp, Chicago, IL 60611 USA., [Jimenez, E.] Orlando Reg Med Ctr Inc, Orlando, FL USA., [Ryan, A.] Washington Hosp Ctr, Washington, DC 20010 USA., [Ryan, A.] Washington Hosp Ctr, 2H, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, 2G, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, 3H, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, 3G, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, 4H, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, CVRR, Washington, DC USA., [Prince, D.] Armadale Hlth Serv, Mount Nasura, WA, Australia., [Edington, J.] Bendigo Hosp, Bendigo, Vic, Australia., [Van Haren, F.] Canberra Hosp, Canberra, ACT, Australia., [Bersten, A.] Flinders Med Ctr, Bedford Pk, SA, Australia., [Hawkins, D. J.] Joondalup Hlth Campus, Joondalup, WA, Australia., [Kilminster, M.] Lismore Base Hosp, Lismore, NSW, Australia., [Sturgess, D.] Mater Adult Hosp, South Brisbane, Qld, Australia., [Ziegenfuss, M.] Prince Charles Hosp, Brisbane, Qld, Australia., [O'Connor, S.] Royal Adelaide Hosp, Adelaide, SA, Australia., [Lipman, J.] Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia., [Campbell, L.] Royal Darwin Hosp, Tiwi, NT, Australia., [Mcallister, R.] Royal Hobart Hosp, Hobart, Tas, Australia., [Roberts, B.] Sir Charles Gairdner Hosp, Nedlands, WA, Australia., [Williams, P.] Queen Elizabeth Hosp, Woodville, SA, Australia., [Parke, R.] Auckland Dist Hlth Board, Auckland, New Zealand., [Seigne, P.] Christchurch Hosp, Christchurch, New Zealand., [Freebairn, R.] Hawkes Bay Hosp, Hastings, New Zealand., [Nistor, D.] Palmerston North Hosp, Midcent Hlth, Palmerston North, New Zealand., [Oxley, C.] Middlemore Hosp, Auckland, New Zealand., [Young, P.] Wellington Hosp, Wellington, New Zealand., [Valentini, R.] Cemic, Buenos Aires, DF, Argentina., [Wainsztein, N.] Fleni, Buenos Aires, DF, Argentina., [Comignani, P.] Hosp Aleman, Buenos Aires, DF, Argentina., [Casaretto, M.] Hosp Cent San Isidro, Buenos Aires, DF, Argentina., [Sutton, G.] Hosp Fernandez, Buenos Aires, DF, Argentina., [Villegas, P.] Hosp Francisco Lopez Lima Area Programa Gen Roca, Gen Roca, Argentina., [Galletti, C.] Sanatorio Allende, Cordoba, Argentina., [Neira, J.] Sanatorio Trinidad Palermo, Buenos Aires, DF, Argentina., [Rovira, D.] Sanatorio Julio Corzo Rosario, Rosario, Santa Fe, Argentina., [Hidalgo, J.] Karl Heusner Mem Hosp, Belize City, Belize., [Hidalgo, J.] Belize Healthcare Partner, Belize City, Belize., [Sandi, F.] Hosp Obrero 1, La Paz, Bolivia., [Caser, E.] Cias Unimed Vitoria, Vitoria, ES, Brazil., [Thompson, M.] Evangelical Hosp Cachoeiro De Itapemirim, Cachoeiro De Itapemirim, Brazil., [D'agostino Dias, M.] Hosp 9 Julho, Sao Paulo, Brazil., [Fontes, L.] Hosp Alcides Carneiro, Petropolis, Brazil., [Lunardi, M.] Hosp Clin Luzia De Pinho Melo, Mogi Das Cruzes, Brazil., [Youssef, N.] Hosp Nacoes Curitiba, Curitiba, Parana, Brazil., [Lobo, S.] Hosp Base Famerp, Sao Jose Do Rio Preto, Brazil., [Silva, R.] Hosp Clin Niteroi, Niteroi, RJ, Brazil., [Sales Jr, J.] Hosp Clin Padre Miguel, Rio De Janeiro, Brazil., [Madeira Campos Melo, L.] Hosp Terapia Intens, Sao Paulo, Brazil., [Oliveira, M.] Hosp Trabalhador, Curitiba, Parana, Brazil., [Fonte, M.] Hosp Esperanza, Olinda, PE, Brazil., [Grion, C.] Hosp Evangel Londrina, Londrina, Brazil., [Feijo, C.] Hosp Geral Fortaleza, Fortaleza, Ceara, Brazil., [Rezende, V] Hosp Geral Roraima, Boa Vista, Brazil., [Assuncao, M.] Hosp Israelita Albert Einstein, Sao Paulo, Brazil., [Neves, A.] Hosp Mater Dei, Belo Horizonte, MG, Brazil., [Gusman, P.; Dalcomune, D.] Hosp Meridional, Cariacica, ES, Brazil., [Teixeira, C.] Hosp Moinhos Vento, Porto Alegre, RS, Brazil., [Kaefer, K.] Hosp Municipal Ruth Cardoso, Balneario, Brazil., [Maia, I] Hosp Nereu Ramos, Florianopolis, SC, Brazil., [Souza Dantas, V] Hosp Pasteur, Rio De Janeiro, Brazil., [Costa Filho, R.] Hosp Pro Cardiaco, Rio De Janeiro, Brazil., [Amorim, F.] Hosp Reg Samambaia, Brasilia, DF, Brazil., [Assef, M.] Hosp Reg Hans Dieter Schmidt, Joinville, Brazil., [Schiavetto, P.] Hosp Santa Casa Campo Mourao, Campo Mourao, PR, Brazil., [Houly, J.] Hosp Santa Paula, Sao Paulo, SP, Brazil., [Houly, J.] Hosp Santapaula, Sao Paulo, Brazil., [Bianchi, F.] Hosp Sao Jose Avai, Itaperuna, RJ, Brazil., [Dias, F.] Hosp Sao Lucas Pucrs, Porto Alegre, RS, Brazil., [Avila, C.] Hosp Sao Vicente Paula, Rio De Janeiro, RJ, Brazil., [Gomez, J.] Hosp Sao Vicente Paulo, Rio De Janeiro, Brazil., [Rego, L.] Hosp Saude Mulher, Belem, Para, Brazil., [Castro, P.] Hosp Tacchini, Bento Goncalves, RS, Brazil., [Passos, J.] Hosp Unimed Costa Do Sol Macae Rj, Macae, RJ, Brazil., [Mendes, C.] Hosp Univ Ufpb Joao Pessoa, Joao Pessoa, Paraiba, Brazil., [Grion, C.] Hosp Univ Londrina, Londrina, Brazil., [Colozza Mecatti, G.] Hosp Univ Sao Francisco, Braganca Paulista, SP, Brazil., [Ferrreira, M.] Santa Casa Caridade Diamantina, Diamantina, MG, Brazil., [Irineu, V] Santa Casa Misericordia Tatui, Tatui, Brazil., [Guerreiro, M.] Sao Francisco de Paula Hosp, Sao Francisco De Paula, RS, Brazil., [Ugarte, S.] Clin Indisa, Providencia, Chile., [Tomicic, V] Clin Las Lilas, Providencia, Chile., [Godoy, C.] Hosp Carlos Van Buren, Valparaiso, Chile., [Samaniego, W.] Hosp Trabajador Santiago, Santiago, Chile., [Escamilla, I] Hosp El Pino, San Bernardo, Chile., [Escamilla, I] Hosp Mutual De Seguridad, Santiago, Chile., [Castro Castro, L.] Ctr Med Imbanaco, Valle Del Cauca, Colombia., [Libreros Duque, G.] Clin Colombia Cali, Cali, Colombia., [Diaz-Guio, D.] Clin Del Cafe, Armenia, Colombia., [Benitez, F.] Clin La Estancia SA, Popayan, Colombia., [Guerra Urrego, A.] Clin Medellin, Medellin, Colombia., [Buitrago, R.] Fdn Clin Shaio, Bogota, Colombia., [Ortiz, G.] Hosp Santa Clara, Bogota, Colombia., [Villalba Gaviria, M.] Hosp Univ Fdn Santa Fe De Bogota, Bogota, Colombia., [Salas, D.] Calderon Guardia Hosp, San Jose, Costa Rica., [Ramirez-Arce, J.] Hosp Dr Rafael Angel Varlderon Guardia Ccss, San Jose, Costa Rica., [Salgado, E.] Clin La Merced, Quito, Ecuador., [Morocho, D.] Hosp Eugenio Espejo, Quito, Ecuador., [Vergara, J.] Hosp Luis Vernaza, Quito, Ecuador., [Chung Sang, M.] Shdug Sistema Hosp Docente De La Univ Guayaquil, Quito, Ecuador., [Orellana-Jimenez, C.] Gen Hosp, San Salvador, El Salvador., [Garrido, L.] Hosp Ctr Med, Guatemala City, Guatemala., [Diaz, O.] Inst Hondureno Seguro Social, La Ceiba, Honduras., [Resiere, D.] Ctr Hosp Univ Ft De France, Fort De France, Martinique, France., [Osorio, C.] Ctr Estatal Cuidados Crit, Salamanca, Mexico., [De La Vega, A.] Ctr Med Nacl 20 Noviembre Issste, Mexico City, DF, Mexico., [Carrillo, R.] Fdn Clin Med Sur, Mexico City, DF, Mexico., [Sanchez, V] Hosp San Jose TEC Monterrey, Monterrey, Mexico., [Villagomez, A.] Hosp 1 Octubre, Issste, Mexico., [Martinez Zubieta, R.] Hosp Espanol Mexico, Mexico City, DF, Mexico., [Sandia, M.] Hosp Gen Ajusco Medio, Mexico City, DF, Mexico., [Zalatiel, M.] Hosp Gen Guadalupe Victoria, Texcoco, Mexico., [Poblano, M.] Hosp Juarez Mexico, Mexico City, DF, Mexico., [Rodriguez Gonzalez, D.] Hosp Civil Guadalajara, Hspitaljuan I Menchaca, Guadalajara, Jalisco, Mexico., [Arrazola, F.; Juan Francisco, L.] Inst Mexicano Seguro Social, Mexico City, DF, Mexico., [Liamendys-Silva, S. A.] Inst Nacl Cancerol, Mexico City, DF, Mexico., [Hernandez, M.] ISSSTE Guerra Moya, Mexico City, DF, Mexico., [Hernandez, M.] Med Ctr ISSEMYM Toluca, Mexico City, DF, Mexico., [Rodriguez Cadena, D.] Mixta, Mexico City, DF, Mexico., [Lopez Islas, I.] Secretaria Salud Dist Fed, Mexico City, DF, Mexico., [Ballesteros Zarzavilla, C.] Hosp Santo Comas, Panama City, Panama., [Matos, A.] Social Secur Hosp, La Chorrera, Panama., [Oyanguren, I] Clin Anglo Amer, Lima, Peru., [Cerna, J.] Essalud, Lima, Peru., [Quispe Sierra, R.] Hosp Nacl Dos De Mayo, Lima, Peru., [Jimenez, R.] Hosp Rebagliati, Lince Dist, Peru., [Castillo, L.] Inst Nacl Enfermedades Neoplas, Surquillo, Peru., [Ocal, R.] Gulhane Med Fac, Istanbul, Turkey., [Sencan, A.] Izmir Ataturk Educ & Res Hosp, Izmir, Turkey., [Gianoni, S. Mareque] CAMS, Montevideo, Uruguay., [Deicas, A.] CASMU, Montevideo, Uruguay., [Hurtado, J.] Hosp Espanol Asse, Montevideo, Uruguay., [Burghi, G.] Hosp Maciel, Montevideo, Uruguay., [Martinelli, A.] Ctr Med Caracas, Caracas, Venezuela., [Von der Osten, I] Hosp Miguel Perez Carreno, Caracas, Venezuela., [Du Maine, C.] MSF Trauma Hosp Kunduz, Kunduz, Afghanistan., [Bhattacharyya, M.] Amri Hosp, Kolkata, India., [Bandyopadhyay, S.] Amri Hosp Salt Lake, Kolkata, W Bengal, India., [Yanamala, S.] Apollo Hosp, Hyderabad, India., [Gopal, P.] Apollo Hosp, Bangalore, Karnataka, India., [Sahu, S.] Apollo Hosp, Bhubaneswar, India., [Ibrahim, M.] Apollo Special Hosp, Chennai, Tamil Nadu, India., [Rathod, D.] Asian Heart Inst, Mumbai, Maharashtra, India., [Mukundan, N.] Baby Mem Hosp Ltd, Calicut, Kerala, India., [Dewan, A.] Batra Hosp & Mrc, New Delhi 110062, India., [Amin, P.] Bombay Hosp Inst Med Sci, Mumbai, Maharashtra, India., [Samavedam, S.] Care Hosp, Hyderabad, India., [Shah, B.] Cims Hosp, Ahmadabad, Gujarat, India., [Gurupal, D.] Columbiaasia Hosp, Mysore, Karnataka, India., [Lahkar, B.] Dispur Hosp, Gauhati, India., [Mandal, A.] Fortis Hosp, Bangalore, Karnataka, India., [Sircar, M.] Fortis Hosp, Noida, India., [Ghosh, S.] Fortis Escorts Hosp, Faridabad, India., [Balasubramani, V] Ganga Med Ctr & Hosp P Ltd, Coimbatore, Tamil Nadu, India., [Kapadia, F.] Hinduja Hosp, Mumbai, Maharashtra, India., [Vadi, S.] KDAH, Mumbai, Maharashtra, India., [Nair, K.] Kerala Inst Med Sci, RMCC, Thiruvananthapuram, Kerala, India., [Tripathy, S.] Kalinga Inst Med Sci, DTEM, Bhubaneswar, Odisha, India., [Nandakumar, S.] Kovai Med Ctr & Hosp, Coimbatore, Tamil Nadu, India., [Sharma, J.] Medanta Medic, Gurgaon, India., [Kar, A.] Med Superspecialty Hosp, Kolkata, W Bengal, India., [Jha, S.] Metro Heart Inst Multispecial, Faridabad, India., [Gurav, K. Zirpe] Ruby Hall Pune, Pune, Maharashtra, India., [Patel, M.] Saifee Hosp, Mumbai, Maharashtra, India., [Bhaysar, A.] Spandan Multispecial Hosp, Vadodara, India., [Samaddar, D.] Tata Main Hosp, Jamshedpur, Jharkhand, India., [Kulkarni, A.] Tata Mem Hosp, Mumbai, Maharashtra, India., [Hashmi, M.] Aga Khan Univ, Karachi, Pakistan., [Ali, W.] Hearts Int Hosp, Rawalpindi, Pakistan., [Nadeem, S.] Liaquat Natl Hosp, Karachi, Pakistan., [Indraratna, K.] Sri Jayewardenepura Gen Hosp, Sri Jayawardenepura Kott, Sri Lanka., [Margarit, A.] Hosp Nostra Senyora Meritxell, Les Escaldes, Andorra., [Urbanek, P.] Akh Wien, Vienna, Austria., [Schlieber, J.] Allgemeines & Orthopad Landeskrankenhaus Stolzalp, Stolzalpe, Austria., [Reisinger, J.] Barmherzige Schwestern Linz, Linz, Austria., [Auer, U.] Gen Hosp Braunau, Braunau, Austria., [Hartjes, A.] Krankenhaus D Barmherzigen Schwestern Ried II, Ried Im Innkreis, Austria., [Lerche, A.] Krankenhaus Floridsdorf, Vienna, Austria., [Janous, T.] LK Gmund Waidhofen Thaya Zwettl, Standort Zwettl, Austria., [Kink, E.] LKH Horgas Enzenbach, Gratwein, Austria., [Krahulec, W.] LKH West, Graz, Austria., [Smolle, K.] Univ Hosp, Graz, Austria., [Van der Schueren, M.] AZ Groeninge Kortrijk, Kortrijk, Belgium., [Thibo, P.] AZ Jan Palfijn Gent, Ghent, Belgium., [Vanhoof, M.] AZ Turnhout, Turnhout, Belgium., [Ahmet, I] Bracops Anderlecht, Anderlecht, Belgium., [Gadisseux, P.] Ctr Hosp Mouscron, Mouscron, Belgium., [Dufaye, P.] CH Peltzer La Tourelle, Verviers, Belgium., [Jacobs, O.] Chirec Edith Cavell, Auderghem, Belgium., [Fraipont, V] CHR Citadelle, Liege, Belgium., [Biston, P.] CHU Charleroi, Charleroi, Belgium., [Dive, A.] CHU Mt Godinne, Yvoir, Belgium., [Bouckaert, Y.] CHU Tivoli, La Louviere, Belgium., [Gilbert, E.] CHwapi, Tournai, Belgium., [Gressens, B.] Clin St Pierre Ottignies, Ottignies, Belgium., [Pinck, E.] Clin Maternite St Elisabeth, Namur, Belgium., [Collin, V] Clin Europe St Michel, Etterbeek, Belgium., [Vincent, J. L.] Erasme Univ Hosp, Anderlecht, Belgium., [De Waele, J.] Ghent Univ Hosp, Ghent, Belgium., [Rimachi, R.] Moliere Hosp, Forest, Belgium., [Gusu, D.] Notre Dame, Brussels, Belgium., [De Decker, K.] Onze Lieve Vrouw Hosp, Aalst, Belgium., [Mandianga, K.] Ixelles Hosp, Ixelles, Belgium., [Heytens, L.] Sint Augustinus, Antwerp, Belgium., [Wittebole, X.] St Luc Univ Hosp UCL, Brussels, Belgium., [Spapen, H.] UZ Brussel, Brussels, Belgium., [Olivier, V] Vivalia Site Libramt, Libramont, Belgium., [Vandenheede, W.] VZW Gezondheidszorg Oostkust Knokke Heist, Knokke Heist, Belgium., [Rogiers, P.] ZNA Middelheim, Antwerp, Belgium., [Kolodzeike, P.] Herning Hosp, Herning, Denmark., [Kruse, M.] Hjoerring Hosp, Hjorring, Denmark., [Andersen, T.] Vejle Hosp, Vejle, Denmark., [Harjola, V] Helsinki Univ Cent Hosp, Helsinki, Finland., [Saarinen, K.] Seinajoki Cent Hosp, Seinajoki, Finland., [Leone, M.] Aix Marseille Univ, Hop Nord, Marseille, France., [Durocher, A.] Calmette Hosp, Lille, France., [Moulront, S.] Ctr Hosp Dunkerque, Dunkerque, France., [Lepape, A.] Ctr Hosp Lyon Sud, Lyon, France., [Losser, M.] CHU Nancy Brabois, Nancy, France., [Cabaret, P.] CH St Philibert, GHICL, Lille, France., [Kalaitzis, E.] CHR Dax, Dax, France., [Zogheib, E.] CHU Amiens, Amiens, France., [Charve, P.] CHU Dijon, Dijon, France., [Francois, B.] CHU Dupuytren, Limoges, France., [Lefrant, J. Y.] CHU Nimes, Nimes, France., [Beilouny, B.] Ctr Hosp Troyes, Troyes, France., [Forceville, X.] Ctr Hosp Meaux, Grp Hosp Est Francilien, Meaux, France., [Misset, B.] Grp Hosp Paris St Joseph, Paris, France., [Jacobs, F.] Hop Antoine Beclere, Clamart, France., [Floccard, B.] Hop Edouard Herriot, Lyon, France., [Payen, D.] Hop Lariboisere, AP HP, Paris, France., [Wynckel, A.] Hop Maison Blanche, Reims, France., [Castelain, V] Hop Univ Strasbourg, Strasbourg, France., [Faure, A.] Hosp Civils Lyon, Lyon, France., [Lavagne, P.] CHU Grenoble, Grenoble, France., [Thierry, I] CHU Nantes, Nantes, France., [Moussa, M.] CHRU Lille, Reanimat Chirurg Cardiovasc, Lille, France., [Vieillard-Baron, A.] Univ Hosp Ambroise Pare, Boulogne, France., [Durand, M.] Univ Hosp Grenoble, La Tronche, France., [Gainnier, M.] Univ Hosp Marseille, Marseille, France., [Ichai, C.] Univ Nice, Nice, France., [Arens, S.] Alexianer Krefeld Gmbh, Krefeld, Germany., [Hoffmann, C.] Charite Hochschulmed Berlin, Berlin, Germany., [Kaffarnik, M.] Charite, Berlin, Germany., [Scharnofske, C.] Diakoniekrankenhaus Henriettenstiftung Gmbh, Hannover, Germany., [Voigt, I] Elisabeth Krankenhaus Essen, Essen, Germany., [Peckelsen, C.] Munich Municipal Hosp Grp, Harlaching Hosp, Munich, Germany., [Weber, M.] Helios St Johannes Klin, Duisburg, Germany., [Gille, J.] Hosp St Georg Leipzig, Leipzig, Germany., [Lange, A.] Klin Hennigsdorf Oberhavel Kliniken Gmbh, Hennigsdorf, Germany., [Schoser, G.] Klin Tettnang, Tettnang, Germany., [Sablotzki, A.] Klinikum St Georg Leipzig, Leipzig, Germany., [Jaschinski, U.; Bluethgen, A.] Klinikum Augsburg, Augsburg, Germany., [Vogel, F.] Klinikum Bremen Mitte, Bremen, Germany., [Tscheu, A.] Klinikum Bremen Ost, Bremen, Germany., [Fuchs, T.] Klinikum Heidenheim, Heidenheim, Germany., [Wattenberg, M.] Klinikum Links Weser Gmbh, Bremen, Germany., [Helmes, T.] Klinikum Luedenscheid, Luedenscheid, Germany., [Scieszka, S.] Krankenhaus Neuwerk, Monchengladbach, Germany., [Heintz, M.] Marienkrankenhaus Schwerte, Schwerte, Germany., [Sakka, S.] Med Ctr Cologne Merheim, Cologne, Germany., [Kohler, J.] Schwarzwald Baar Klinikum Villingen Schwenningen, Villingen Schwenningen, Germany., [Fiedler, F.] St Elisabeth Krankenhaus Koln Hohenlind, Cologne, Germany., [Danz, M.] St Martinus Hosp Olpe, Olpe, Germany., [Sakr, Y.] Uniklinikum Jena, Jena, Germany., [Riessen, R.] Univ Klinikum Tubingen, Tubingen, Germany., [Kerz, T.] Univ Med Mainz, Mainz, Germany., [Kersten, A.] Univ Hosp Aachen, CPACC, Aachen, Germany., [Tacke, F.] Univ Hosp Aachen, DMIII, Aachen, Germany., [Marx, G.] Univ Hosp Aachen, OIC, Aachen, Germany., [Volkert, T.] Univ Hosp Muenster, Munster, Germany., [Schmutz, A.] Univ Med Ctr Freiburg, Fr

The article considers the issues of monitoring of the educational institutions official websites in the Republic of Belarus, beginning with the 2018 interms of its influence on the potential of services export in education. Special attention is paid to a state and development of information resources of higher education institutions. Regulatory legal acts and other documents forming a normative basis of monitoring are analyzed. The organization of monitoring processes of the education institutions websites is considered in the manual regime as well as using the utomated information system for auditing education institutions information resources in the Republic of Belarus, assessment of their state and relevance is also considered (AIS Monitoring). The criteria for evaluation of the websites included in monitoring are presented and their comparison at the manual and automated way of realization is carried out. The analysis of monitoring results of the education institutions official websites in 2018 including that realized within trial operation of AIS Monitoring is produced. The correlation between the growth in the number of foreign students in higher education institutions and indicators for monitoring of information resources is assessed. The results of a quantitative assessment of the dependence of the growth rate of the number of foreign students at Belarusian universities on the level of compliance with the requirements for the informational content of official sites in terms of the list and cost of services provided in the form of a regression model are presented. Recommendations for further development and improvement of monitoring processes of information resources are formed.

Background: The objective of the study is to evaluate clinical and radiographic outcomes in patients treated with limited-open retrograde intramedullary headless screw (IMHS) fixation for metacarpal neck and shaft fractures. Methods: Retrospective review of 91 consecutive patients (79 men; 12 women), mean age 28 (range =15-69) years, treated with IMHS fixation for acute displaced metacarpal neck (N = 56) and shaft (N = 35) fractures at a single institution. Mean follow-up was 10 (range = 1-71, median = 3) months. Preoperative mean magnitude of metacarpal neck angulation was 48° (range = 0°-90°), and mean shaft angulation was 42° (range = 0°-70°). Active motion was initiated within 5 days postoperatively. Clinical outcomes were assessed with digital goniometry, grip strength, and return to full activity. The time to radiographic union and radiographic arthrosis was assessed. Results: All 91 patients achieved full functional arc of metacarpophalangeal (MCP) motion, and all achieved full active MCP extension or hyperextension. At mean follow-up of 10 months, postoperative mean MCP joint flexion-extension arc was 88° (range = 55°-110°). Grip strength was available for 52 patients and measured 104.1% of the contralateral hand (range = 58%-230%). Radiographic union data were available for 86 patients. Seventy-six percent (65/86) achieved radiographic union by the end of week 6 (range = 2-10 weeks). Early arthrosis was noted in 1 patient at the MCP. There were 3 cases of shaft refracture after recurrent blunt trauma, following prior evidence of full osseous union. Conclusions: The IMHS fixation is safe, reliable, and durable for metacarpal neck/subcapital, axially stable shaft fractures, and select delayed unions or malunions. It allows for early postoperative motion without affecting union rates and obviates immobilization. This technique offers distinct advantages over formal open reduction and percutaneous Kirschner wire techniques.

In the article we examine relevant problems regarding human rights on roads with arising digitalized processes. The problems cover three aspects. First, are the rights of drivers, passengers, and impaired individuals who use digitalized management systems while on the roads. Second, is the protection of the rights of those who are dismissed from driving the public transport with digitalized management systems. Third, is the potential danger to the society from economic outcomes of further digitalization. In the end, the article gives a comprehensive argument about the importance of securing human rights on the roads as it was brought up to our attention by the United Nations.Following the afore mentioned aspects of the problem, the article derives hypothetical solutions regarding human rights of road users with arising digitalized process. First of all, it remains essential to reinforce drivers’ rules on the roads. Next, safety of pedestrians, people who are travelling on foot, needs to be ensured since they are worse off in case of an emergency on the roads. Finally, it is a special focus on ensuring the rights of persons with disabilities. The latter applies not only to the drivers and pedestrians, but also to passengers with disabilities who use the means of urban ground transportation.

INTRODUCTION/AIMS Temporary vocal fold injection (VFI) is a common treatment for acute and subacute vocal fold paralysis (VFP). Laryngeal electromyography (LEMG) is useful for diagnosing neurogenic causes of VFP. This study evaluated whether the presence of VFI material prevents interpretation of LEMG in patients with acute and subacute VFP. METHODS Patients with acute and subacute unilateral VFP (onset ≤6 mo) who underwent temporary VFI within 3 mo preceding LEMG were evaluated. A matched control group that did not undergo VFI was also studied. The LEMG team (laryngologist and electromyographer) performed and interpreted LEMG using a pre-specified protocol, including qualitative and quantitative motor unit analysis. RESULTS Eighteen patients with VFI underwent LEMG successfully with interpretation of spontaneous activity and motor unit recruitment. Fourteen patients were seen in follow-up to determine accuracy of established LEMG prognosis. Seven of seven subjects with poor LEMG prognosis did not recover vocal fold motion. Five of seven subjects with fair LEMG prognosis recovered vocal fold motion. Findings were similar for the control group. DISCUSSION VFI augmentation material did not prevent interpretation of meaningful LEMG data in patients with acute and subacute VFP, and accurate prognoses of vocal fold motion recovery were established.

No research exists on how body mass index (BMI) changes with age over the full life span and social disparities therein. This study aims to fill the gap using an innovative life-course research design and analytic methods to model BMI trajectories from early adolescence to old age across 20th-century birth cohorts and test sociodemographic variation in such trajectories. We conducted the pooled integrative data analysis (IDA) to combine data from four national population-based NIH longitudinal cohort studies that collectively cover multiple stages of the life course (Add Health, MIDUS, ACL, and HRS) and estimate mixed-effects models of age trajectories of BMI for men and women. We examined associations of BMI trajectories with birth cohort, race/ethnicity, parental education, and adult educational attainment. We found higher mean levels of and larger increases in BMI with age across more recent birth cohorts as compared with earlier-born cohorts. Black and Hispanic excesses in BMI compared with Whites were present early in life and persisted at all ages, and, in the case of Black–White disparities, were of larger magnitude for more recent cohorts. Higher parental and adulthood educational attainment were associated with lower levels of BMI at all ages. Women with college-educated parents also experienced less cohort increase in mean BMI. Both race and education disparities in BMI trajectories were larger for women compared with men.

Biological aging is a proposed mechanism through which social determinants drive health disparities. We conducted proof-of-concept testing of eight DNA-methylation and blood-chemistry quantifications of biological aging as mediators of disparities in healthspan between Black and White participants in the United States Health and Retirement Study (HRS; n=9005). We quantified biological aging from four DNA-methylation “clocks” (Horvath, Hannum, PhenoAge, and GrimAge), a DNA-methylation Pace of Aging (DunedinPoAm), and three blood-chemistry measures (PhenoAge, Klemera-Doubal method Biological Age, and homeostatic dysregulation). We quantified Black-White disparities in healthspan from cross-sectional and longitudinal data on physical-performance tests, self-reported activities of daily living (ADL) limitations and physician-diagnosed chronic diseases, self-rated health, and survival. DNA-methylation and blood-chemistry quantifications of biological aging were moderately correlated (Pearson-r range 0.1-0.4). GrimAge, DunedinPoAm and all three blood-chemistry measures were associated with healthspan characteristics (e.g. mortality effect-size range 1.71-2.32) and showed evidence of more advanced/faster biological aging in Black compared with White participants (Cohen’s d=.4-.5). These measures accounted for 13-95% of Black-White differences in healthspan-related characteristics. Findings that Black Americans are biologically older and aging more rapidly than White Americans of the same chronological age suggest that eliminating disparities in the pace of aging can contribute building to aging health equity.

Objectives: Previous work showed that higher polyp mast cell load correlated with worse postoperative endoscopic appearance in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Polyp epithelial mast cells showed increased expression of T-cell/transmembrane immunoglobulin and mucin domain protein 3 (TIM-3), a receptor that promotes mast cell activation and cytokine production. In this study, CRSwNP patients were followed post-operatively to investigate whether mast cell burden or TIM-3 expression among mast cells can predict recalcitrant disease. Methods: Nasal polyp specimens were obtained via functional endoscopic sinus surgery (FESS) and separated into epithelial and stromal layers via enzymatic digestion. Mast cells and TIM-3-expressing mast cells were identified via flow cytometry. Mann-Whitney U tests and Cox proportional hazard models assessed whether mast cell burden and TIM-3 expression were associated with clinical outcomes, including earlier recurrence of polypoid edema and need for treatment with steroids. Results: Twenty-three patients with CRSwNP were studied and followed for 6 months after undergoing FESS. Higher mast cell levels were associated with earlier recurrence of polypoid edema: epithelial HR = 1.283 ( P = .02), stromal HR = 1.103 ( P = .02). Percent of mast cells expressing TIM-3 in epithelial or stromal layers was not significantly associated with earlier recurrence of polypoid edema. Mast cell burden and TIM-3+ expression were not significantly associated with need for future treatment with steroids post-FESS. Conclusions: Mast cell load in polyp epithelium and stroma may predict a more refractory postoperative course for CRSwNP patients. The role of TIM-3 in the chronic inflammatory state seen in CRSwNP remains unclear.

With the publication of the 4th edition of the dictionary by prof. Breitman, we have completed a great work on medical lexicography. One can disagree with the author's peculiar spelling like "gynecology", "Pasteur", etc., but one can in no way dispute the value and necessity of this manual for our time. The absence of such reference books on the book market, as well as the doctor's ignorance of a foreign language, often puts him in a difficult position when he wants to establish the exact pronunciation, spelling or meaning of a clinical term. Therefore, the dictionary of prof. Breitman will undoubtedly serve for a long time to be a reliable reference in all matters concerning clinical terminology. It is very good that the author also gives an indication of the pronunciation of surnames and proper names. At this point, everyone may be puzzled. The dictionary will solve them. In this note, we will allow ourselves to note some errors and controversies regarding terms in the interest of correcting them for the 2nd edition.