Butler University

This document represents the first collaboration between 2 organizations-the American Society for Parenteral and Enteral Nutrition and the Society of Critical Care Medicine-to describe best practices in nutrition therapy in critically ill children. The target of these guidelines is intended to be the pediatric critically ill patient (>1 month and <18 years) expected to require a length of stay >2-3 days in a PICU admitting medical, surgical, and cardiac patients. In total, 2032 citations were scanned for relevance. The PubMed/MEDLINE search resulted in 960 citations for clinical trials and 925 citations for cohort studies. The EMBASE search for clinical trials culled 1661 citations. In total, the search for clinical trials yielded 1107 citations, whereas the cohort search yielded 925. After careful review, 16 randomized controlled trials and 37 cohort studies appeared to answer 1 of the 8 preidentified question groups for this guideline. We used the GRADE criteria (Grading of Recommendations, Assessment, Development, and Evaluation) to adjust the evidence grade based on assessment of the quality of study design and execution. These guidelines are not intended for neonates or adult patients. The guidelines reiterate the importance of nutrition assessment-particularly, the detection of malnourished patients who are most vulnerable and therefore may benefit from timely intervention. There is a need for renewed focus on accurate estimation of energy needs and attention to optimizing protein intake. Indirect calorimetry, where feasible, and cautious use of estimating equations and increased surveillance for unintended caloric underfeeding and overfeeding are recommended. Optimal protein intake and its correlation with clinical outcomes are areas of great interest. The optimal route and timing of nutrient delivery are areas of intense debate and investigations. Enteral nutrition remains the preferred route for nutrient delivery. Several strategies to optimize enteral nutrition during critical illness have emerged. The role of supplemental parenteral nutrition has been highlighted, and a delayed approach appears to be beneficial. Immunonutrition cannot be currently recommended. Overall, the pediatric critical care population is heterogeneous, and a nuanced approach to individualizing nutrition support with the aim of improving clinical outcomes is necessary.

Urbanization contributes to the loss of the world's biodiversity and the homogenization of its biota. However, comparative studies of urban biodiversity leading to robust generalities of the status and drivers of biodiversity in cities at the global scale are lacking. Here, we compiled the largest global dataset to date of two diverse taxa in cities: birds (54 cities) and plants (110 cities). We found that the majority of urban bird and plant species are native in the world's cities. Few plants and birds are cosmopolitan, the most common being Columba livia and Poa annua. The density of bird and plant species (the number of species per km(2)) has declined substantially: only 8% of native bird and 25% of native plant species are currently present compared with estimates of non-urban density of species. The current density of species in cities and the loss in density of species was best explained by anthropogenic features (landcover, city age) rather than by non-anthropogenic factors (geography, climate, topography). As urbanization continues to expand, efforts directed towards the conservation of intact vegetation within urban landscapes could support higher concentrations of both bird and plant species. Despite declines in the density of species, cities still retain endemic native species, thus providing opportunities for regional and global biodiversity conservation, restoration and education.

No abstract available.

PRELIMINARY REMARKS (INTENT OF GUIDELINES) A.S.P.E.N. and SCCM are both nonprofit organizations composed of multidisciplinary healthcare professionals. The mission of A.S.P.E.N. is to improve patient care by advancing the science and practice of clinical nutrition and metabolism. The mission of SCCM is to secure the highest quality care for all critically ill and injured patients. Guideline Limitations: These A.S.P.E.N.−SCCM Clinical Guidelines are based on general conclusions of health professionals who, in developing such guidelines, have balanced potential benefits to be derived from a particular mode of medical therapy against certain risks inherent with such therapy. However, practice guidelines are not intended as absolute requirements. The use of these practice guidelines does not in any way project or guarantee any specific benefit in outcome or survival. The judgment of the healthcare professional based on individual circumstances of the patient must always take precedence over the recommendations in these guidelines. The guidelines offer basic recommendations that are supported by review and analysis of the current literature, other national and international guidelines, and a blend of expert opinion and clinical practicality. The population of critically ill patients in an intensive care unit (ICU) is not homogeneous. Many of the studies on which the guidelines are based are limited by sample size, patient heterogeneity, variability in disease severity, lack of baseline nutritional status, and insufficient statistical power for analysis. Periodic Guideline Review and Update: This particular report is an update and expansion of guidelines published by A.S.P.E.N. and SCCM in 2009 (1). Governing bodies of both A.S.P.E.N. and SCCM have mandated that these guidelines be updated every three to five years. The database of randomized controlled trials (RCTs) that served as the platform for the analysis of the literature was assembled in a joint "harmonization process" with the Canadian Clinical Guidelines group. Once completed, each group operated separately in their interpretation of the studies and derivation of guideline recommendations (2). The current A.S.P.E.N. and SCCM guidelines included in this paper were derived from data obtained via literature searches by the authors through December 31, 2013. Although the committee was aware of landmark studies published after this date, these data were not included in this manuscript. The process by which the literature was evaluated necessitated a common end date for the search review. Adding a last-minute landmark trial would have introduced bias unless a formalized literature search was re-conducted for all sections of the manuscript. Target Patient Population for Guideline: The target of these guidelines is intended to be the adult (≥ 18 years) critically ill patient expected to require a length of stay (LOS) greater than 2 or 3 days in a medical ICU (MICU) or surgical ICU (SICU). The current guidelines were expanded to include a number of additional subsets of patients who met the above criteria, but were not included in the previous 2009 guidelines. Specific patient populations addressed by these expanded and updated guidelines include organ failure (pulmonary, renal, and liver), acute pancreatitis, surgical subsets (trauma, traumatic brain injury [TBI], open abdomen [OA], and burns), sepsis, postoperative major surgery, chronic critically ill, and critically ill obese. These guidelines are directed toward generalized patient populations but, like any other management strategy in the ICU, nutrition therapy should be tailored to the individual patient. Target Audience: The intended use of these guidelines is for all healthcare providers involved in nutrition therapy of the critically ill, primarily physicians, nurses, dietitians, and pharmacists. Methodology: The authors compiled clinical questions reflecting key management issues in nutrition therapy. A committee of multidisciplinary experts in clinical nutrition composed of physicians, nurses, pharmacists, and dietitians was jointly convened by the two societies. Literature searches were then performed using key words (critically ill, critical care, intensive care, nutrition, enteral, parenteral, tube feeding, and those related to assigned topics such as pancreatitis, sepsis, etc.) to evaluate the quality of evidence supporting a response to those questions, which were then used to derive a subsequent treatment recommendation. The literature search included MEDLINE, PubMed, Cochrane Database of Systemic Reviews, the National Guidelines Clearing House and an Internet search using the Google search engine for scholarly articles through an end date of December 31, 2013 (including ePub publications). While preference was given to RCTs, other forms of resource material were used to support the response, including nonrandomized cohort trials, prospective observational studies, and retrospective case series. Use of publications was limited to full-text articles available in English on adult humans. For all included RCTs, two readers completed data abstraction forms (DAFs) examining the data and assessing the quality of the research methodology to produce a shared evaluation achieved by consensus for each study (example of DAF provided in the supplemental data, Supplemental Digital Content 1, https://links.lww.com/CCM/B571). DAFs were constructed only for RCTs. When the strongest available evidence was a published meta-analysis, the studies from the meta-analysis were used to determine the quality of the evidence and assessed by two evidence assessors. The data from included trials were entered into Review Manager 5.2 software to create forest plots aggregating the effect size for each intervention and outcome (3). The key forest plots supporting the recommendation are included throughout the text and in the supplement data (Supplemental Digital Content 1, https://links.lww.com/CCM/B571). No new forest plots were created when a meta-analysis was evaluated. Since release of the 2009 A.S.P.E.N. and SCCM Clinical Guidelines, the concepts of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group have been adopted (4–7). A full description of the methodology has been previously published (4). The data from the Review Manager analysis was uploaded to GRADEPro software (8), where the body of evidence for a given intervention and outcome was evaluated for overall quality. One analyst created each GRADE table that was then independently confirmed by a second analyst. The GRADE tables are provided in the supplement data (Supplemental Digital Content 1, https://links.lww.com/CCM/B571). Due to the inordinately large number of RCTs evaluated, observational studies were critically reviewed, but not utilized to construct the GRADE tables. However, in the few cases where observational studies were the only available evidence in a population, their quality of evidence was reviewed, using GRADE (Table 1). When no RCT or observational study was available to answer a question directly, consensus of the author group on the best clinical practice approach was used, and the recommendation was designated "based on expert consensus."TABLE 1: Type of EvidenceA recommendation for clinical practice was based on both the best available evidence and the risks and benefits to patients. While small author teams developed each recommendation and provided the supporting rationale, a full discussion by the entire author group followed, and every committee member was polled anonymously for their agreement with the recommendation. Achievement of consensus was arbitrarily set at 70% agreement of authors with a particular recommendation. Only one recommendation (H3a) did not meet this level of agreement, with a final consensus of 64%. All other consensus-based recommendations reached a level of agreement of 80% or higher. As with all A.S.P.E.N. and SCCM clinical guidelines, this manuscript was subjected to rigorous peer review by clinical content experts from all the practice disciplines that would use the guidelines, both internal and external to the organizations. A summary of the guidelines is presented in the supplement data (Supplemental Digital Content 1, https://links.lww.com/CCM/B571). A nutrition bundle based on the top guidelines (as voted on by the committee) for the bedside practitioner is presented in Table 2.TABLE 2: Bundle StatementsCONFLICT OF INTEREST All authors completed both an A.S.P.E.N. and SCCM conflict of interest form for copyright assignment and financial disclosure. There was no input or funding from industry, nor were any industry representatives present at any of the committee meetings. DEFINITIONS Nutrition Therapy refers specifically to the provision of either enteral nutrition (EN) by enteral access device and/or parenteral nutrition (PN) by central venous access. Standard therapy (STD) refers to provision of IV fluids, no EN or PN, and advancement to oral diet as tolerated. INTRODUCTION The significance of nutrition in the hospital setting (and especially the ICU) cannot be overstated. Critical illness is typically associated with a catabolic stress state in which patients demonstrate a systemic inflammatory response coupled with complications of increased infectious morbidity, multiple organ dysfunction, prolonged hospitalization, and disproportionate mortality. Over the past three decades, exponential advances have been made in the understanding of the molecular and biological effects of nutrients in maintaining homeostasis in the critically ill population. Traditionally, nutrition support in the critically ill population was regarded as adjunctive care designed to provide exogenous fuels to preserve lean body mass and support the patient throughout the stress response. Recently this strategy has evolved to represent nutrition therapy, in which the feeding is thought to help attenuate the metabolic response to stress, prevent oxidative cellular injury, and favorably modulate immune responses. Improvement in the clinical course of critical illness may be achieved by early EN, appropriate macro- and micronutrient delivery, and meticulous glycemic control. Delivering early nutrition support therapy, primarily by the enteral route, is seen as a proactive therapeutic strategy that may reduce disease severity, diminish complications, decrease LOS in the ICU, and favorably impact patient outcomes. A. NUTRITION ASSESSMENT Question: Does the use of a nutrition risk indicator identify patients who will most likely benefit from nutrition therapy? A1. Based on expert consensus, we suggest a determination of nutrition risk (for example, Nutritional Risk Score [NRS-2002], NUTRIC score) be performed on all patients admitted to the ICU for whom volitional intake is anticipated to be insufficient. High nutrition risk identifies those patients most likely to benefit from early EN therapy. Rationale: Poor outcomes have been associated with inflammation generated by critical illness that leads to deterioration of nutrition status and malnutrition (9). However, malnutrition in the critically ill has always been difficult to define. An international consensus group modified definitions to recognize the impact of inflammation. Objective measures of baseline nutrition status have been described by A.S.P.E.N. and the Academy of Nutrition and Dietetics (10, 11). On the other hand, nutrition risk is easily defined and more readily determined by evaluation of baseline nutrition status and assessment of disease severity. All hospitalized patients are required to undergo an initial nutrition screen within 48 hours of admission. However, patients at higher nutrition risk in an ICU setting require a full nutrition assessment. Many screening and assessment tools are used to evaluate nutrition status, such as the Mini Nutritional Assessment (MNA), the Malnutrition Universal Screening Tool (MUST), the Short Nutritional Assessment Questionnaire (SNAQ), the Malnutrition Screening Tool (MST), and the Subjective Global Assessment (SGA) (12). However, only the NRS-2002 and the NUTRIC score determine both nutrition status and disease severity. Although both scoring systems were based on retrospective analysis, they have been used to define nutrition risk in RCTs in critically ill patients (13–16). Patients at "risk" are defined by an NRS-2002 > 3 and those at "high risk" with a score ≥ 5; or a NUTRIC score ≥ 5 (if interleukin-6 is not included, otherwise ≥ 6) (13, 18). Interleukin-6 is rarely available as a component for the NUTRIC score; therefore, Heyland et al has shown a NUTRIC score ≥ 5 still indicates high nutrition risk (19). Two prospective nonrandomized studies show that patients at high nutrition risk are more likely to benefit from early EN with improved outcome (reduced nosocomial infection, total complications, and mortality) than patients at low nutrition risk (13, 18). While widespread use and supportive evidence is somewhat lacking to date, improvement in these scoring systems may increase their applicability in the future by providing guidance as to the role of EN and PN in the ICU. Question: What additional tools, components or surrogate markers provide useful information when performing nutrition assessments in critically ill adult patients? A2. Based on expert consensus, we suggest that nutritional assessment include an evaluation of comorbid conditions, function of the gastrointestinal (GI) tract, and risk of aspiration. We suggest not using traditional nutrition indicators or surrogate markers, as they are not validated in critical care. Rationale: In the critical care setting, the traditional serum protein markers (albumin, prealbumin, transferrin, retinol-binding protein) are a reflection of the acute phase response (increases in vascular permeability and reprioritization of hepatic protein synthesis) and do not accurately represent nutrition status in the ICU setting (20). Anthropometrics are not reliable in assessment of nutrition status or adequacy of nutrition therapy (21). Individual levels of calcitonin, C-reactive protein (CRP), IL-1, tumor necrosis factor (TNF), IL-6, and citrulline are still investigational and should not be used as surrogate markers. Ultrasound is emerging as a tool to expediently measure muscle mass and determine changes in muscle tissue at bedside in the ICU, given its ease of use and availability (22, 23). A CT scan provides a precise quantification of skeletal muscle and adipose tissue depots; however it is quite costly unless a scan taken for other purposes is used to determine body composition (24, 25). Both may be valuable future tools to incorporate into nutrition assessment; however, validation and reliability studies in ICU patients are still pending. Assessment of muscle function is still in its infancy. Its measurement, reproducibility, and applicability are still being validated for use in critically ill patients, and may be of value in the future. Question: What is the best method for determining energy needs in the critically ill adult patient? A3a. We suggest that indirect calorimetry (IC) be used to determine energy requirements, when available and in the absence of variables that affect the accuracy of measurement. [Quality of Evidence: Very Low] A3b. Based on expert consensus, in the absence of IC, we suggest that a published predictive equation or a simplistic weight-based equation (25–30 kcal/kg/day) be used to determine energy requirements. (See section Q for obesity recommendations.) Rationale: Clinicians should determine energy requirements in order to establish the goals of nutrition therapy. Energy requirements may be calculated either through simplistic formulas (25–30 kcal/kg/day), published predictive equations, or IC. The applicability of IC may be limited at most institutions by availability and cost. Variables in the ICU that affect the timing and accuracy of IC measurements include the presence of air leaks or chest tubes, supplemental oxygen (e.g., nasal cannula, bilevel positive airway pressure), ventilator settings (fractional inspiratory oxygen and positive end-expiratory pressure), continuous renal replacement therapy (CRRT), anesthesia, physical therapy, and excessive movement (26). More than 200 predictive equations have been published in the literature, with accuracy rates ranging from 40–75% when compared to IC, and no single equation emerges as being more accurate in an ICU (27–32). Predictive equations are less accurate in obese and underweight patients (33–36). Equations derived from testing hospital patients (Penn State, Ireton-Jones, Swinamer) are no more accurate than equations derived from testing normal volunteers (Harris-Benedict, Mifflin St. Jeor) (37). The poor accuracy of predictive equations is related to many non-static variables affecting energy expenditure in the critically ill patient, such as weight, medications, treatments, and body temperature. The only advantage of using weight-based equations over other predictive equations is simplicity. However, in critically ill patients following aggressive volume resuscitation or in the presence of edema or anasarca, clinicians should use dry or usual body weight in these equations. Additional energy provided by dextrose-containing fluids and lipid-based medications such as propofol should be accounted for when deriving nutrition therapy regimens to meet target energy goals. Achieving energy balance as guided by IC measurements compared to predictive equations may lead to more appropriate nutrition intake. While two RCTs (38, 39) that met our inclusion criteria (with data from 161 patients) showed that higher mean intake of energy and protein were provided in IC-directed study patients compared to controls whose nutrition therapy was directed by predictive equations, issues with study design prevent a stronger recommendation for use of IC. In a study of burn patients, use of IC-directed nutrition therapy helped provide the minimal effective intake, avoiding the excesses of overfeeding seen in controls whose therapy was directed by the Curreri formula. Complications between groups (diarrhea and hyperglycemia) were no different, but traditional outcome parameters were not evaluated (38). A second study in general ICU patients used both EN and PN to meet target energy goals determined by IC measurement or a weight-based predictive equation (25 kcal/kg/day) (39). While the IC-directed energy goal was no different than the value obtained by predictive equation (1976 ± 468 vs 1838 ± 468 kcal/day, respectively, p = 0.60), only study patients were monitored vigilantly by an ICU dietitian, while controls were managed by standard of care (less frequent ICU dietitian monitoring), which led to significantly more energy and protein per in the study patients. The toward in study patients compared to controls = p = is difficult to in of their increased with to ICU LOS vs p = and of vs p = (38, by IC or by predictive equations, energy expenditure should be more than per and to energy and protein intake should be used Question: protein provision be monitored independently from energy provision in critically ill adult patients? Based on expert consensus, we suggest an evaluation of adequacy of protein provision be Rationale: In the critical care setting, protein to be the most for supporting immune and maintaining lean body For most critically ill patients, protein requirements are higher than energy requirements and are not easily met by provision of enteral have a high Patients with EN to frequent may benefit from protein The to protein should be based on an assessment of adequacy of protein intake. equations (e.g., may be used to adequacy of protein provision by the of protein to that especially when balance studies are not available to needs section protein markers (albumin, prealbumin, transferrin, are not validated for determining adequacy of protein provision and should not be used in the critical care setting in this EN Question: What is the benefit of early EN in critically ill adult patients compared to or this therapy? We that nutrition support therapy in the form of early EN be within hours in the critically ill patient who is to volitional intake. [Quality of Evidence: Very Low] Rationale: EN the of the by maintaining between the and the release of as and EN by maintaining and supporting the mass of and that the tissue and in to tissue at such as the and in permeability from of is a that is within hours of the major or The of the permeability changes include increased of with risk for systemic infection, and greater of multiple organ As disease in permeability are and the enteral of feeding is more likely to favorably impact outcome parameters of infection, organ and hospital LOS The specific for providing EN are to modulate stress and the systemic immune response, and attenuate disease Additional of EN therapy may include use of the as a for the of and use of enteral as an effective for stress previous data from RCTs early One meta-analysis of trials by Heyland showed a toward = p = when EN was within 48 hours compared to of EN after that A second meta-analysis of trials by showed in infectious = p = and hospital LOS p = when early EN was on within hours of ICU A meta-analysis of trials by showed a in = p = and = p = but no in multiple organ failure when early EN was within hours of to the ICU, compared to EN after that an updated meta-analysis of RCTs that met our inclusion criteria the provision of early EN EN, all on with on of early EN was associated with a in = p = and infectious = p = compared to early EN EN or 1: enteral nutrition (EN) vs EN, 2: enteral nutrition (EN) vs EN, infectious a in outcome between the use of EN or PN for adult critically ill patients? We suggest the use of EN over PN in critically ill patients who require nutrition support therapy. [Quality of Evidence: to Very Low] Rationale: In the of critically ill patients it is and to use EN of The effects of EN compared to PN are in RCTs a of patient populations in critical including injury, major surgery, and acute While few studies have shown a effect on the most outcome effect from EN is a in infectious and central in most patient and in patients) and ICU previous EN to PN showed in infectious with use of EN complications = p = and hospital LOS mean = p = were seen with use of EN compared to PN in one of the by of the showed no in between the two of nutrition support therapy One meta-analysis by showed a significantly = p = a significantly higher of infectious complications = p = with use of PN compared to EN In studies patients that met our inclusion criteria, on which was shown to be significantly less with EN than PN = p ICU LOS was with EN compared to PN by one full = to p = LOS and were not significantly These in outcome from the of feeding from studies and may diminish in the future with in glycemic medical management and new nutrition (EN) vs parenteral nutrition infectious the clinical evidence of required to EN in critically ill adult patients? Based on expert consensus, we suggest in the of and patient while should be evaluated when EN, of should not be required to of Rationale: The literature the that and evidence of or are not required for of in the ICU setting in of patients, on the medications, and metabolic state of ICU and postoperative are related to of the and mass of has been defined (e.g., absence or high etc.) and to in to of patients on are only of and do not to or The for EN of the of is based on studies of which critically ill surgical patients) the and of EN within the initial hours of to the ICU. or may greater disease and Patients with normal have been shown to have ICU than those with or vs vs ICU LOS has been shown to increase with greater number of of days when to days with of of EN is with a greater number of of A greater number of of may increased as EN is and may clinical Question: What is the level of of EN within the for critically ill patients? does the level of of EN affect patient We that the level of be in the in those critically ill patients at high risk for section or those who have shown to [Quality of Evidence: to Based on expert consensus we suggest in most critically ill patients, it is to EN in the Rationale: EN therapy in the is and may decrease the to of The of level of the of the feeding tube is in the different of the or or the within the may be determined by patient within ICU and of small enteral access and

Amid soaring health spending, there is growing interest in workplace disease prevention and wellness programs to improve health and lower costs. In a critical meta-analysis of the literature on costs and savings associated with such programs, we found that medical costs fall by about $3.27 for every dollar spent on wellness programs and that absenteeism costs fall by about $2.73 for every dollar spent. Although further exploration of the mechanisms at work and broader applicability of the findings is needed, this return on investment suggests that the wider adoption of such programs could prove beneficial for budgets and productivity as well as health outcomes.

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.

Philosophers of science typically associate the causal-mechanical view of scientific explanation with the work of Railton and Salmon. In this paper I shall argue that the defects of this view arise from an inadequate analysis of the concept of mechanism. I contrast Salmon's account of mechanisms in terms of the causal nexus with my own account of mechanisms, in which mechanisms are viewed as complex systems. After describing these two concepts of mechanism, I show how the complex-systems approach avoids certain objections to Salmon's account of causal-mechanical explanation. I conclude by discussing how mechanistic explanations can provide understanding by unification.

The authors argue that perceptions of service quality vary across cultural groups, as defined by each culture’s position on Hofstede’s dimensions. They explicitly map the relationship between service quality perceptions and cultural dimension positions and draw the implications for international service market segmentation. They also test the hypotheses constituting their theoretical analysis. They show that the importance of SERVQUAL dimensions is correlated with Hofstede’s cultural dimensions. They also used the correlation coefficients to compute a Cultural Service Quality Index that could be used to segment international service markets and allocate resources across segments.

Examines the relative importance of service recovery in determining overall satisfaction and behavioral intentions. Recommendations include suggestions for implementing a service recovery program and for encouraging dissatisfied customers to complain.

This book argues for a new image of nature and of science—one that understands both natural and social phenomena to be the product of mechanisms, and that suggests that much of the work of natural and social scientists involves discovering, describing, and explaining how these mechanisms work. The book explores the interplay between ontological questions about mechanisms as things in the world and methodological questions about how these mechanisms can be characterized. Ontologically, mechanisms are understood to be collections of entities whose organized activities and interactions give rise to phenomena. This minimal conception of mechanism is abstract enough to encompass most of the wide variety of things that scientists have called mechanisms. While mechanisms are particular things, localized in space and time, the models that scientists use to describe them must be abstract and idealized. The mechanistic approach provides new ways of thinking about traditional metaphysical questions—for instance, about the nature of objects, part-whole and cause-effect relations, properties and universals, natural kinds, and laws of nature. It also suggests novel approaches for thinking about methodological questions concerning scientific representation, causal inference, reduction, and scientific explanation. The New Mechanical Philosophy offers the promise of a better understanding of the sources of both the unity and diversity of science.

We develop and estimate a medium scale macroeconomic model that allows for unemployment and staggered nominal wage contracting. In contrast to most existing quantitative models, employment adjustment is on the extensive margin and the employment of existing workers is efficient. Wage rigidity, however, affects the hiring of new workers. The former is introduced via the staggered Nash bargaining setup of Gertler and Trigari (2006) . A robust finding is that the model with wage rigidity provides a better description of the data than does a flexible wage version. Overall, the model fits the data roughly as well as existing quantitative macroeconomic models, such as Smets and Wouters (2007) or Christiano, Eichenbaum, and Evans (2005) . More work is necessary, however, to ensure a robust identification of the key labor market parameters.

A large number of studies have attempted to identify factors that are correlated with exporting success. However, much controversy exists about the key determinants of export performance and their relative importance. A major reason for this lack of consensus is the absence of a unified measure for capturing export performance. In this study, an attempt is made to develop a generalized export performance measure, the EXPERF scale, that can be applied to multiple countries. Results from a survey of top executives of U.S. and Japanese exporters support a three-dimensional scale for measuring export performance. The three dimensions of the export performance (EXPERF) scale are financial export performance, strategic export performance, and satisfaction with export venture. Implications of the study for further research and managerial practice are also discussed.

Abstract Some firms grow very rapidly; others much more slowly. Potential explanations for differences in performance levels between high growth firms and low growth firms operating in the same industry are sought by comparing the firms' founding strategies. Results indicate that founding strategies of high and low growth firms differ systematically among the firms studied.

Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables.

Many open access journals have a reputation for being of low quality and being dishonest with regard to peer review and publishing costs. Such journals are labeled “predatory” journals. This study examines author profiles for some of these “predatory” journals as well as for groups of more well‐recognized open access journals. We collect and analyze the publication record, citation count, and geographic location of authors from the various groups of journals. Statistical analyses verify that each group of journals has a distinct author population. Those who publish in “predatory” journals are, for the most part, young and inexperienced researchers from developing countries. We believe that economic and sociocultural conditions in these developing countries have contributed to the differences found in authorship between “predatory” and “nonpredatory” journals.

Some recent studies have shown that culture influences how consumers perceive service quality. Others have shown the relationship between perceived service quality and behavioral intentions. In this article, the authors study how culture influences behavioral intentions toward services on the basis of services marketing and cross-cultural psychology literature. They tested and found that customers from cultures with lower individualism or higher uncertainty avoidance tend to have a higher intention to praise if they received superior service. On the other hand, the same groups tend not to switch, give negative word of mouth, or complain even if they received poor service quality. Customers from cultures with higher individualism or lower uncertainty avoidance tend to switch, engage in negative word of mouth, or complain if they received poor service quality. But they do not tend to praise when they received superior service. Managerial implications, contribution, and future research directions are also discussed.

The developments of the open-source OpenMolcas chemistry software environment since spring 2020 are described, with a focus on novel functionalities accessible in the stable branch of the package or via interfaces with other packages. These developments span a wide range of topics in computational chemistry and are presented in thematic sections: electronic structure theory, electronic spectroscopy simulations, analytic gradients and molecular structure optimizations, ab initio molecular dynamics, and other new features. This report offers an overview of the chemical phenomena and processes OpenMolcas can address, while showing that OpenMolcas is an attractive platform for state-of-the-art atomistic computer simulations.

Intraperitoneal injection of a sublethal dose of lipopolysaccharide (LPS) into mice resulted in the appearance of tumor necrosis factor (TNF) in the serum within 45 min. Maximal serum TNF was detected by 1 h, and by 3-4 h TNF levels were no longer significantly above baseline. Injection of mice with an additional dose of LPS at 4 h resulted in no further increase in serum TNF. The in vivo kinetics of TNF appearance correlated with in vitro studies in which TNF mRNA was detected in murine peritoneal macrophages 30 min after LPS stimulation. The increase in serum TNF was not detected in mice treated with dexamethasone, 3 mg/kg, prior to LPS stimulation. The decrease in TNF correlated with the appearance of significant amounts of endogenous serum corticosterone which were maximal by 3 h. Further evidence for the role of endogenous steroids in the modulation of serum TNF levels was obtained in studies with adrenalectomized or hypophysectomized mice. Compared to sham-operated animals, serum TNF levels remain elevated 5 h post LPS stimulation in adrenalectomized or hypophysectomized mice. In contrast with the transient increase in TNF, serum IL 1 was maximal 4 h post LPS injection and remained elevated at 24 h. In vitro studies with primary cultures of human peripheral blood monocytes and human umbilical cord vein endothelial cells demonstrated that LPS-induced monocyte IL 1 levels were reduced approximately 5-fold by 10(-7) M dexamethasone while dexamethasone had only minimal effects on endothelial cell IL 1. Therefore, the in vitro data would suggest that the maintenance of elevated IL 1 levels coincident with the appearance of endogenous corticosteroids during LPS shock is related to the synthesis of IL 1 by both monocyte-macrophages and non-myeloid cell populations including endothelial cells.

This study examined how restricted and repetitive behaviors and interests (RRBs) developed over time in a sample of children with autism spectrum disorders (ASD). One hundred ninety-two children referred for a diagnosis of autism at age 2, and 22 children with nonspectrum development disorders were evaluated with a battery of cognitive and diagnostic measures at age 2 and subsequently at ages 3, 5, and 9. Factor analysis of the RRB items on the Autism Diagnostic Interview-Revised revealed two RRB factors at each wave of data collection, one comprising "repetitive sensorimotor" (RSM) behaviors and the other "insistence on sameness" (IS) behaviors. For children with ASD, RSM scores remained relatively high over time, indicating consistent severity, whereas IS scores started low and increased over time, indicating worsening. Having a higher nonverbal intelligence (NVIQ) at age 2 was associated with milder concurrent RSM behaviors and with improvement in these behaviors over time. There was no relationship between NVIQ at age 2 and IS behaviors. However, milder social/communicative impairment, at age 2 was associated with more severe concurrent IS behaviors. Trajectory analysis revealed considerable heterogeneity in patterns of change over time for both kinds of behaviors. These findings are discussed in terms of their implications for our understanding of RRBs in ASD and other disorders, making prognoses about how RRBs will develop in children with ASD as they get older, and using RRBs to identify ASD phenotypes in genetic studies.

Purpose The paper aims to examine the effect of good corporate governance practices on corporate transparency and performance of Malaysian listed companies. Design/methodology/approach Samples were selected using matched‐sampling method and hierarchical regression was employed to test the relationship between among corporate governance mechanism, transparency and performance. Findings Corporate governance factors have a strong predicting power on company performance, mainly due to debt monitoring and foreign ownership. However, there is a significant negative relation between audit quality and performance. The results find that performance is not associated with the level of disclosure and timely reporting. The results indicate that disclosure and timeliness are not significant contributing factors in the relationship between corporate governance and market performance. Research limitations/implications The data covers a one‐year period of 2002 only. This paper deals only with “one‐way” causality running from corporate governance mechanisms to performance, even though, there is evidence of “reverse‐way” and “two‐way” causality in governance literature. Practical implications This paper indicates that internal governance mechanisms are not important determinants to corporate performance. However, governance in forms of debt monitoring and foreign ownership have significant influence on corporate performance. Transparency (i.e. disclosure and timeliness of reporting) is not a significant mediating variable between corporate governance and performance. Originality/value Distinct from previous empirical research as the disclosure level is measured using self‐designed corporate governance index. Apart from a study conducted in an Asian setting of Malaysia, the study also tests transparency as a mediating variable between corporate governance and performance