Central Michigan University

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

BACKGROUND: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. METHODS: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. RESULTS: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). CONCLUSIONS: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.).

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Turmeric, a spice that has long been recognized for its medicinal properties, has received interest from both the medical/scientific world and from culinary enthusiasts, as it is the major source of the polyphenol curcumin. It aids in the management of oxidative and inflammatory conditions, metabolic syndrome, arthritis, anxiety, and hyperlipidemia. It may also help in the management of exercise-induced inflammation and muscle soreness, thus enhancing recovery and performance in active people. In addition, a relatively low dose of the complex can provide health benefits for people that do not have diagnosed health conditions. Most of these benefits can be attributed to its antioxidant and anti-inflammatory effects. Ingesting curcumin by itself does not lead to the associated health benefits due to its poor bioavailability, which appears to be primarily due to poor absorption, rapid metabolism, and rapid elimination. There are several components that can increase bioavailability. For example, piperine is the major active component of black pepper and, when combined in a complex with curcumin, has been shown to increase bioavailability by 2000%. Curcumin combined with enhancing agents provides multiple health benefits. The purpose of this review is to provide a brief overview of the plethora of research regarding the health benefits of curcumin.

ABSTRACT This paper introduces a general class of distributions generated from the logit of the beta random variable. A special case of this family is the beta-normal distribution. The shape properties of the beta-normal distribution are discussed. Estimation of parameters of the beta-normal distribution by the maximum likelihood method is also discussed. The beta-normal distribution provides great flexibility in modeling not only symmetric heavy-tailed distributions, but also skewed and bimodal distributions. The flexibility of this distribution is illustrated by applying it to two empirical data sets and comparing the results to previously used methods.

Although workplace harassment affects the lives of many employees, until recently it has been relatively ignored in the organizational psychology literature. First, the authors introduced an attribution- and reciprocity-based model that explains the link between harassment and its potential causes and consequences. The authors then conducted a meta-analysis to examine the potential antecedents and consequences of workplace harassment. As shown by the meta-analysis, both environmental and individual difference factors potentially contributed to harassment and harassment was negatively related to the well-being of both individual employees and their employing organizations. Furthermore, harassment contributed to the variance in many outcomes, even after controlling for 2 of the most commonly studied occupational stressors, role ambiguity and role conflict.

Summary Species detection using environmental DNA ( eDNA ) has tremendous potential for contributing to the understanding of the ecology and conservation of aquatic species. Detecting species using eDNA methods, rather than directly sampling the organisms, can reduce impacts on sensitive species and increase the power of field surveys for rare and elusive species. The sensitivity of eDNA methods, however, requires a heightened awareness and attention to quality assurance and quality control protocols. Additionally, the interpretation of eDNA data demands careful consideration of multiple factors. As eDNA methods have grown in application, diverse approaches have been implemented to address these issues. With interest in eDNA continuing to expand, supportive guidelines for undertaking eDNA studies are greatly needed. Environmental DNA researchers from around the world have collaborated to produce this set of guidelines and considerations for implementing eDNA methods to detect aquatic macroorganisms. Critical considerations for study design include preventing contamination in the field and the laboratory, choosing appropriate sample analysis methods, validating assays, testing for sample inhibition and following minimum reporting guidelines. Critical considerations for inference include temporal and spatial processes, limits of correlation of eDNA with abundance, uncertainty of positive and negative results, and potential sources of allochthonous DNA . We present a synthesis of knowledge at this stage for application of this new and powerful detection method.

Objective. In the course of daily teaching responsibilities, pharmacy educators collect rich data that can provide valuable insight into student learning. This article describes the qualitative data analysis method of content analysis, which can be useful to pharmacy educators because of its application in the investigation of a wide variety of data sources, including textual, visual, and audio files. Findings. Both manifest and latent content analysis approaches are described, with several examples used to illustrate the processes. This article also offers insights into the variety of relevant terms and visualizations found in the content analysis literature. Finally, common threats to the reliability and validity of content analysis are discussed, along with suitable strategies to mitigate these risks during analysis. Summary. This review of content analysis as a qualitative data analysis method will provide clarity and actionable instruction for both novice and experienced pharmacy education researchers.

Quantitative synthesis of data from single-case designs (SCDs) is becoming increasingly common in psychology and education journals. Because researchers do not ordinarily report numerical data in addition to graphical displays, reliance on plot digitizing tools is often a necessary component of this research. Intercoder reliability of data extraction is a commonly overlooked, but potentially important, step of this process. The purpose of this study was to examine the intercoder reliability and validity of WebPlotDigitizer (Rohatgi, 2015), a web-based plot digitizing tool for extracting data from a variety of plots, including XY coordinates of interrupted time-series data. Two coders extracted 3,596 data points from 168 data series in 36 graphs across 18 studies. Results indicated high levels of intercoder reliability and validity. Implications of and recommendations based on these results are discussed in relation to researchers involved in quantitative synthesis of data from SCDs.

OBJECTIVE: To present best-practice recommendations for the prevention, recognition, and treatment of exertional heat illnesses (EHIs) and to describe the relevant physiology of thermoregulation. BACKGROUND: Certified athletic trainers recognize and treat athletes with EHIs, often in high-risk environments. Although the proper recognition and successful treatment strategies are well documented, EHIs continue to plague athletes, and exertional heat stroke remains one of the leading causes of sudden death during sport. The recommendations presented in this document provide athletic trainers and allied health providers with an integrated scientific and clinically applicable approach to the prevention, recognition, treatment of, and return-to-activity guidelines for EHIs. These recommendations are given so that proper recognition and treatment can be accomplished in order to maximize the safety and performance of athletes. RECOMMENDATIONS: Athletic trainers and other allied health care professionals should use these recommendations to establish onsite emergency action plans for their venues and athletes. The primary goal of athlete safety is addressed through the appropriate prevention strategies, proper recognition tactics, and effective treatment plans for EHIs. Athletic trainers and other allied health care professionals must be properly educated and prepared to respond in an expedient manner to alleviate symptoms and minimize the morbidity and mortality associated with these illnesses.

Graphite intercalation compounds (GICs) have attracted tremendous attention due to their exceptional properties that can be finely tuned by controlling the intercalation species and concentrations. Here, we report for the first time that potassium (K) ions can electrochemically intercalate into graphitic materials, such as graphite and reduced graphene oxide (RGO) at ambient temperature and pressure. Our experiments reveal that graphite can deliver a reversible capacity of 207 mAh/g. Combining experiments with ab initio calculations, we propose a three-step staging process during the intercalation of K ions into graphite: C → KC24 (Stage III) → KC16 (Stage II) → KC8 (Stage I). Moreover, we find that K ions can also intercalate into RGO film with even higher reversible capacity (222 mAh/g). We also show that K ions intercalation can effectively increase the optical transparence of the RGO film from 29.0% to 84.3%. First-principles calculations suggest that this trend is attributed to a decreased absorbance produced by K ions intercalation. Our results open opportunities for novel nonaqueous K-ion based electrochemical battery technologies and optical applications.

Abstract A brief historical perspective relating the discovery of dendrimers and other dendritic polymers is presented. Dendritic polymers are recognized as the fourth major class of macromolecular architecture consisting of four sub‐ classes, namely, (1) random hyperbranched, (2) dendrigrafts, (3) dendrons, and (4) dendrimers. The previous literature is reviewed with anecdotal events leading to implications for dendrimers in the emerging science of nanotechnology. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2719–2728, 2002

Importance: Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. Objective: To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19). Setting, Design, and Participants: Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement. Exposure: SARS-CoV-2. Main Outcomes and Measures: Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19. Results: Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P < .001), higher C-reactive protein level (median, 152 mg/L vs 33 mg/L; P < .001), and lower platelet count (<150 ×103 cells/μL [212/523 {41%} vs 84/486 {17%}, P < .001]). A total of 398 patients (73.8%) with MIS-C and 253 (43.8%) with COVID-19 were admitted to the intensive care unit, and 10 (1.9%) with MIS-C and 8 (1.4%) with COVID-19 died during hospitalization. Among patients with MIS-C with reduced left ventricular systolic function (172/503, 34.2%) and coronary artery aneurysm (57/424, 13.4%), an estimated 91.0% (95% CI, 86.0%-94.7%) and 79.1% (95% CI, 67.1%-89.1%), respectively, normalized within 30 days. Conclusions and Relevance: This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19.

A narrative review was conducted to examine the current state of the utilisation of telemedicine amid the current COVID-19 pandemic and to evaluate the benefits of continuing telemedicine usage in the future. A literature review was performed for articles related to telemedicine. Databases including PubMed, Google Scholar, Cochrane Library and Ovid MEDLINE were searched. Three reviewers independently performed article selection based on relevance to our topic. We included all articles between 1990 and 2020 related to telemedicine using the following keywords: 'telemedicine', 'telehealth', 'policy', 'COVID-19', 'regulation', 'rural', 'physical examination', 'future'. A total of 60 articles were identified, and through careful selection we narrowed the final number of articles to 42 based on relevance to our topic. Telemedicine has been rapidly evolving over the past several decades. Issues with regulation and reimbursement have prevented its full immersion into the healthcare system. During the current pandemic, Centers for Medicare and Medicaid services have expanded access to telemedicine services. The advantages of telemedicine moving forward include its cost-effectiveness, ability to extend access to specialty services and its potential to help mitigate the looming physician shortage. Disadvantages include lack of available technological resources in certain parts of the country, issues with security of patient data, and challenges in performing the traditional patient examination. It is critically important that changes are made to fully immerse telemedicine services into the healthcare landscape in order to be prepared for future pandemics as well as to reap the benefits of this service in the future.

There has been a considerable amount of research in the development of sustainable water treatment techniques capable of improving the quality of water. Unavailability of drinkable water is a crucial issue especially in regions where conventional drinking water treatment systems fail to eradicate aquatic pathogens, toxic metal ions and industrial waste. The research and development in this area have given rise to a new class of processes called advanced oxidation processes, particularly in the form of heterogeneous photocatalysis, which converts photon energy into chemical energy. Advances in nanotechnology have improved the ability to develop and specifically tailor the properties of photocatalytic materials used in this area. This paper discusses many of those photocatalytic nanomaterials, both metal-based and metal-free, which have been studied for water and waste water purification and treatment in recent years. It also discusses the design and performance of the recently studied photocatalytic reactors, along with the recent advancements in the visible-light photocatalysis. Additionally, the effects of the fundamental parameters such as temperature, pH, catalyst-loading and reaction time have also been reviewed. Moreover, different techniques that can increase the photocatalytic efficiency as well as recyclability have been systematically presented, followed by a discussion on the photocatalytic treatment of actual wastewater samples and the future challenges associated with it.

Earnings management is of great concern to corporate stakeholders. While numerous studies have investigated the effects of various corporate governance and audit quality variables on earnings management, empirical evidence is rather inconsistent. This meta‐analysis identifies 12 significant relationships by integrating results from 48 prior studies. For corporate governance, the independence of the board of directors and its expertise have a negative relationship with earnings management. Similar negative relationships exist between earnings management and the audit committee's independence, its size, expertise, and the number of meetings. The audit committee's share ownership has a positive effect on earnings management. For audit quality, auditor tenure, auditor size, and specialization have a negative relationship with earnings management. Auditor independence, as measured by fee ratio and total fee, is also a deterrent to earnings management.

La recherche sur les antécédents et les conséquences de l’ajustement des expatriés a été revue de façon qualitative et avec la méthode quantitative de méta‐analyse. Les prédicteurs individuels, environnementaux, reliés au travail et reliés à la famille, de l’ajustement général, interactionnel et au travail ont été analysés. L’efficacité personnelle, la fréquence des interactions dans le pays hôte, et le soutien familial ont prédit les trois types d’ajustement. De plus, des compétences élevées en relations interpersonnelles ont été associées à un meilleur ajustement à l’environnement en général. Les résultats ont également démontré que la variable “conflit de rôle”était corrélée négativement avec l’ajustement au travail alors que l’ambiguïté du rôle et la discrétion ont été associés avec l’ajustement au travail. Un modèle d’équations structurelles a été développé avec les corrélations agrégées pour illustrer les relations causales possibles impliquant un facteur général d’ajustement et les résultats des tensions au travail, la satisfaction au travail, l’engagement organisationnel, l’intention de quitter, ainsi que la performance au travail. L’hypothèse était que l’ajustement influencerait les tensions et la satisfaction au travail et que ces deux dernières variables auraient un effet sur l’engagement organisationnel, la performance et l’intention de quitter. Le modèle a bien correspondu aux données. Research on the antecedents and consequences of expatriate adjustment was reviewed using meta‐analytic methods. The antecedents and outcomes of three facets of adjustment were examined. Self‐efficacy, frequency of interaction with host nationals, and family support consistently predicted all three types of adjustment. In addition, better interpersonal skills were associated with greater adjustment to general environment. Greater cultural novelty was associated with less interactional adjustment. Role conflict, ambiguity, and discretion were also strong predictors of work adjustment. A structural equations model that illustrated causal relationships involving expatriate adjustment and outcomes of job strain, job satisfaction, organisational citizenship, intent to turnover, and job performance generated a good fit with the data.

Electronic sports, cybersports, gaming, competitive computer gaming, and virtual sports are all synonyms for the term eSports. Regardless of the term used, eSports is now becoming more accepted as a sport and gamers are being identified as athletes within society today. eSports has even infiltrated higher education in the form of an intercollegiate athletic sport, as two university athletic departments have made eSports an official varsity sport where scholarships are provided to collegiate eSports athletes. Thus, the intertwining of eSports and university athletics brings into question whether eSports should be considered sport by broader society. This article provides a brief history of eSports, a further developed definition of eSports, and a comparison of eSports to traditional philosophical and sociological definitions of sport. The purpose of this article is to provoke thought on the academically accepted definitions of sport and debate whether eSports should be considered a sport. Attention will be given to the following components of sport: play, organization, competition, skill, physicality, broad following, and institutionalization.

BACKGROUND: Our primary objective was to demonstrate the utility and feasibility of the intraoperative assessment of colon and rectal perfusion using fluorescence angiography (FA) during left-sided colectomy and anterior resection. Anastomotic leak (AL) after colorectal resection increases morbidity, mortality, and, in cancer cases, recurrence rates. Inadequate perfusion may contribute to AL. The PINPOINT Endoscopic Fluorescence Imaging System allows for intraoperative assessment of anastomotic perfusion. STUDY DESIGN: This is a prospective, multicenter, open-label, clinical trial that assessed the feasibility and utility of FA for intraoperative perfusion assessment during left-sided colectomy and anterior resection at 11 centers in the United States. RESULTS: A total of 147 patients were enrolled, of whom 139 were eligible for analysis. Diverticulitis (44%), rectal cancer (25%), and colon cancer (21%) were the most prevalent indications for surgery. The mean level of anastomosis was 10 ± 4 cm from the anal verge. Splenic-flexure mobilization was performed in 81% and high ligation of the inferior mesenteric artery in 61.9% of patients. There was a 99% success rate for FA, and FA changed surgical plans in 11 (8%) patients, with the majority of changes occurring at the time of transection of the proximal margin (7%). Overall morbidity rates were 17%. The anastomotic leak rate was 1.4% (n = 2). There were no anastomotic leaks in the 11 patients who had a change in surgical plan based on intraoperative perfusion assessment with FA. CONCLUSIONS: PINPOINT is a safe and feasible tool for intraoperative assessment of tissue perfusion during colorectal resection. There were no anastomotic leaks in patients in whom the anastomosis was revised based on inadequate perfusion with FA.

Interviewing children for investigative purposes is a specialized skill. Professional interviewers need to be able to conduct interviews that bear scrutiny from outside agencies and also serve the best interests of children. In clear, engaging language, this eye-opening book corrects the common misunderstandings about adult-child conversational exchanges and provides guidelines for interviews, based on the most up-to-date research. It also presents a flexible protocol that can be tailored to meet individual needs. Topics discussed include: The current child protection crisis The difficulties of investigating alleged abuse cases Children's strengths and weaknesses as interviewees Characteristics of the most respected protocols Children's language development and understanding of interview rules Ancillary techniques, such as the use of drawings and anatomically detailed dolls How to improve one's decision-making skills How to stay abreast of the latest research and techniques The principles outlined in his book can be generalized to a variety of situations in which the interviewer wishes to gather information untainted by the dynamics of adult-child questioning. Thus, Investigative Interviews of Children will be invaluable not only to child protection workers, lawyers, law enforcement officers, and psychologists, but also to other mental health professionals, educators, and parents.