Indiana University South Bend

Presented are a profile of a sample of earnings manipulators, their distinguishing characteristics, and a suggested model for detecting manipulation. The model's variables are designed to capture either the financial statement distortions that can result from manipulation or preconditions that might prompt companies to engage in such activity. The results suggest a systematic relationship between the probability of manipulation and some financial statement variables. This evidence is consistent with the usefulness of accounting data in detecting manipulation and assessing the reliability of reported earnings. The model identifies approximately half of the companies involved in earnings manipulation prior to public discovery. Because companies that are discovered manipulating earnings see their stocks plummet in value, the model can be a useful screening device for investment professionals. The screening results, however, require determination of whether the distortions in the financial statement numbers result from earnings manipulation or have another structural root.

Environmental DNA (eDNA) refers to the genetic material that can be extracted from bulk environmental samples such as soil, water, and even air. The rapidly expanding study of eDNA has generated unprecedented ability to detect species and conduct genetic analyses for conservation, management, and research, particularly in scenarios where collection of whole organisms is impractical or impossible. While the number of studies demonstrating successful eDNA detection has increased rapidly in recent years, less research has explored the ''ecology'' of eDNA-myriad interactions between extraorganismal genetic material and its environment-and its influence on eDNA detection, quantification, analysis, and application to conservation and research. Here, we outline a framework for understanding the ecology of eDNA, including the origin, state, transport, and fate of extraorganismal genetic material. Using this framework, we review and synthesize the findings of eDNA studies from diverse environments, taxa, and fields of study to highlight important concepts and knowledge gaps in eDNA study and application. Additionally, we identify frontiers of conservation-focused eDNA application where we see the most potential for growth, including the use of eDNA for estimating population size, population genetic and genomic analyses via eDNA, inclusion of other indicator biomolecules such as environmental RNA or proteins, automated sample collection and analysis, and consideration of an expanded array of creative environmental samples. We discuss how a more complete understanding of the ecology of eDNA is integral to advancing these frontiers and maximizing the potential of future eDNA applications in conservation and research.

Using data from 17 years of a large and nationally representative panel study from Germany, the authors examined whether there is a set point for life satisfaction (LS)--stability across time, even though it can be perturbed for short periods by life events. The authors found that 24% of respondents changed significantly in LS from the first 5 years to the last 5 years and that stability declined as the period between measurements increased. Average LS in the first 5 years correlated .51 with the 5-year average of LS during the last 5 years. Height, weight, body mass index, systolic and diastolic blood pressure, and personality traits were all more stable than LS, whereas income was about as stable as LS. Almost 9% of the sample changed an average of 3 or more points on a 10-point scale from the first 5 to last 5 years of the study.

BACKGROUND: We observed that the prodrug clopidogrel was less effective in inhibiting platelet aggregation with coadministration of atorvastatin during point-of-care platelet function testing. Because atorvastatin is metabolized by cytochrome P450 (CYP) 3A4, we hypothesized that clopidogrel might be activated by CYP3A4. METHODS AND RESULTS: Platelet aggregation was measured in 44 patients undergoing coronary artery stent implantation treated with clopidogrel or clopidogrel plus pravastatin or atorvastatin, and in 27 volunteers treated with clopidogrel and either erythromycin or troleandomycin, CYP3A4 inhibitors, or rifampin, a CYP3A4 inducer. Atorvastatin, but not pravastatin, attenuated the antiplatelet activity of clopidogrel in a dose-dependent manner. Percent platelet aggregation was 34+/-23, 58+/-15 (P=0.027), 74+/-10 (P=0.002), and 89+/-7 (P=0.001) in the presence of clopidogrel and 0, 10, 20, and 40 mg of atorvastatin, respectively. Erythromycin attenuated platelet aggregation inhibition (55+/-12 versus 42+/-12% platelet aggregation; P=0.002), as did troleandomycin (78+/-18 versus 45+/-18% platelet aggregation; P<0.0003), whereas rifampin enhanced platelet aggregation inhibition (33+/-18 versus 56+/-20% platelet aggregation, P=0.001). CONCLUSIONS: CYP3A4 activates clopidogrel. Atorvastatin, another CYP3A4 substrate, competitively inhibits this activation. Use of a statin not metabolized by CYP3A4 and point-of-care platelet function testing may be warranted in patients treated with clopidogrel.

BACKGROUND: Interindividual variability of platelet inhibition after aspirin or clopidogrel administration has been described. Additionally, aspirin resistance and clopidogrel resistance occur in some individuals. Because the prodrug clopidogrel is activated by hepatic cytochrome P450 (CYP) 3A4, we hypothesized that interindividual variability in clopidogrel efficacy might be related to interindividual differences in CYP3A4 metabolic activity. METHODS AND RESULTS: Platelet aggregation was measured before and after clopidogrel treatment in 32 patients undergoing coronary artery stent implantation and in 35 healthy volunteers. The erythromycin breath test was used to measure CYP3A4 activity in vivo in 25 of the healthy volunteers. Individual platelet aggregation was studied in 10 healthy volunteers after the coadministration of clopidogrel and rifampin (a CYP3A4 inducer). Clopidogrel nonresponders, low responders, and responders were defined by a relative inhibition of adenosine diphosphate (20 micromol/L)-induced platelet aggregation of <10%, 10% to 29%, and > or =30%, respectively. Among patients, 22% were clopidogrel nonresponders, 32% were low responders, and 47% were responders. Among volunteers, 16% were nonresponders, 12% were low responders, and 72% were responders. Percent platelet aggregation after clopidogrel inversely correlated with CYP3A4 activity (r=-0.6, P=0.003). Improved platelet inhibition in volunteers resistant to clopidogrel was observed with the coadministration of clopidogrel and rifampin. CONCLUSIONS: Clopidogrel administration results in interindividual variability in platelet inhibition, which correlates with CYP3A4 metabolic activity. Measurement of antiplatelet drug efficacy with a point-of-care device and alternative antithrombotic strategies for aspirin or clopidogrel nonresponders and low responders could reduce the incidence of thrombotic events that continue to occur despite oral antiplatelet therapy.

BACKGROUND: We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy. METHODS: In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3-receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide-doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point. RESULTS: In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P=0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P=0.002), and the overall 120-hour period (37% vs. 22%, P=0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P=0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2. CONCLUSIONS: Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.).

Intermittent-flow respirometry is an experimental protocol for measuring oxygen consumption in aquatic organisms that utilizes the best features of closed (stop-flow) and flow-through respirometry while eliminating (or at least reducing) some of their inherent problems. By interspersing short periods of closed-chamber oxygen consumption measurements with regular flush periods, accurate oxygen uptake rate measurements can be made without the accumulation of waste products, particularly carbon dioxide, which may confound results. Automating the procedure with easily available hardware and software further reduces error by allowing many measurements to be made over long periods thereby minimizing animal stress due to acclimation issues. This paper describes some of the fundamental principles that need to be considered when designing and carrying out automated intermittent-flow respirometry (e.g. chamber size, flush rate, flush time, chamber mixing, measurement periods and temperature control). Finally, recent advances in oxygen probe technology and open source automation software will be discussed in the context of assembling relatively low cost and reliable measurement systems.

Abstract The purpose of this research was to construct scales to measure the Islamic work ethic and individualism and to provide evidence of these scales' reliability and validity. Three steps were involved: a literature search to develop statements pertaining to the Islamic work ethic and individualism; screening of the initial statements by Islamic experts; and actual administration of the refined statements to a sample of 150 Arab students. The results of a reliability test and correlation analysis indicated that both scales were reliable and that the Islamic Work Ethic Scale was positively and significantly correlated with the Individualism Scale.

The Greenland shark (Somniosus microcephalus), an iconic species of the Arctic Seas, grows slowly and reaches >500 centimeters (cm) in total length, suggesting a life span well beyond those of other vertebrates. Radiocarbon dating of eye lens nuclei from 28 female Greenland sharks (81 to 502 cm in total length) revealed a life span of at least 272 years. Only the smallest sharks (220 cm or less) showed signs of the radiocarbon bomb pulse, a time marker of the early 1960s. The age ranges of prebomb sharks (reported as midpoint and extent of the 95.4% probability range) revealed the age at sexual maturity to be at least 156 ± 22 years, and the largest animal (502 cm) to be 392 ± 120 years old. Our results show that the Greenland shark is the longest-lived vertebrate known, and they raise concerns about species conservation.

SIGNIFICANCE: Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not, administration of antioxidants is ineffective, suggesting that our current understanding of the underlying regulatory processes is incomplete. Recent Advances: Similar to reactive oxygen species and reactive nitrogen species, reactive sulfur species are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism, and mitochondrial function. To rationalize the complexity of chemical interactions of reactive species with themselves and their targets and help define their role in systemic metabolic control, we here introduce a novel integrative concept defined as the reactive species interactome (RSI). The RSI is a primeval multilevel redox regulatory system whose architecture, together with the physicochemical characteristics of its constituents, allows efficient sensing and rapid adaptation to environmental changes and various other stressors to enhance fitness and resilience at the local and whole-organism level. CRITICAL ISSUES: To better characterize the RSI-related processes that determine fluxes through specific pathways and enable integration, it is necessary to disentangle the chemical biology and activity of reactive species (including precursors and reaction products), their targets, communication systems, and effects on cellular, organ, and whole-organism bioenergetics using system-level/network analyses. FUTURE DIRECTIONS: Understanding the mechanisms through which the RSI operates will enable a better appreciation of the possibilities to modulate the entire biological system; moreover, unveiling molecular signatures that characterize specific environmental challenges or other forms of stress will provide new prevention/intervention opportunities for personalized medicine. Antioxid. Redox Signal. 00, 000-000.

Computed tomography enables 3D anatomic imaging at a high spatial resolution, but requires delivery of an x-ray contrast agent to distinguish tissues with similar or low x-ray attenuation. Gold nanoparticles (AuNPs) have gained recent attention as an x-ray contrast agent due to exhibiting a high x-ray attenuation, nontoxicity and facile synthesis and surface functionalization for colloidal stability and targeted delivery. Potential diagnostic applications include blood pool imaging, passive targeting and active targeting, where actively targeted AuNPs could enable molecular imaging by computed tomography. This article summarizes the current state of knowledge for AuNP x-ray contrast agents within a paradigm of key structure-property-function relationships in order to provide guidance for the design of AuNP contrast agents to meet the necessary functional requirements in a particular application. Functional requirements include delivery to the site of interest (e.g., blood, tumors or microcalcifications), nontoxicity during delivery and clearance, targeting or localization at the site of interest and contrast enhancement for the site of interest compared with surrounding tissues. Design is achieved by strategically controlling structural characteristics (composition, mass concentration, size, shape and surface functionalization) for optimized properties and functional performance. Examples from the literature are used to highlight current design trade-offs that exist between the different functional requirements.

Hydrogen sulfide (H(2)S) is rapidly emerging as a biologically significant signaling molecule. Studies published before 2000 report low or undetectable H(2)S (usually as total sulfide) levels in blood or plasma, whereas recent work has reported sulfide concentrations between 10 and 300 microM, suggesting it acts as a circulating signal. In the first series of experiments, we used a recently developed polarographic sensor to measure the baseline level of endogenous H(2)S gas and turnover of exogenous H(2)S gas in real time in blood from numerous animals, including lamprey, trout, mouse, rat, pig, and cow. We found that, contrary to recent reports, H(2)S gas was essentially undetectable (<100 nM total sulfide) in all animals. Furthermore, exogenous sulfide was rapidly removed from blood, plasma, or 5% bovine serum albumin in vitro and from intact trout in vivo. To determine if blood H(2)S could transiently increase, we measured oxygen-dependent H(2)S production by trout hearts in vitro and in vivo. H(2)S has been shown to mediate ischemic preconditioning (IPC) in mammals. IPC is present in trout and, unlike mammals, the trout myocardium obtains its oxygen from relatively hypoxic systemic venous blood. In vitro, myocardial H(2)S production was inversely related to Po(2), whereas we failed to detect H(2)S in ventral aortic blood from either normoxic or hypoxic fish in vivo. These results provide an autocrine or paracrine mechanism for myocardial coupling of hypoxia to H(2)S in IPC, i.e., oxygen sensing, but they fail to provide any evidence that H(2)S signaling is mediated by the circulation.

Online retailers are increasingly using information technologies to provide value-added services to customers. Prominent examples of these services are online recommender systems and consumer feedback mechanisms, both of which serve to reduce consumer search costs and uncertainty associated with the purchase of unfamiliar products. The central question we address is how recommender systems affect sales. We take into consideration the interaction among recommendations, sales, and price. We then develop a robust empirical model that incorporates the indirect effect of recommendations on sales through retailer pricing, potential simultaneity between sales and recommendations, and a comprehensive measure of the strength of recommendations. Applying the model to a panel data set collected from two online retailers, we found that the strength of recommendations has a positive effect on sales. Moreover, this effect is moderated by the recency effect, where more recently released recommended items positively affect the cross-selling efforts of sellers. We also show that recommender systems help to reinforce the long-tail phenomenon of electronic commerce, and obscure recommendations positively affect cross-selling. We also found a positive effect of recommendations on prices. These results suggest that recommendations not only improve sales but they also provide added flexibility to retailers to adjust their prices. A comparative analysis reveals that recommendations have a higher effect on sales than does consumer feedback. Our empirical results show that providing value-added services, such as digital word of mouth and recommendations, allows retailers to charge higher prices while at the same time increasing demand by providing more information regarding the quality and match of products.

New data are reported from the operation of a 4.0-kg ${\mathrm{CF}}_{3}\mathrm{I}$ bubble chamber in the 6800-foot-deep SNOLAB underground laboratory. The effectiveness of ultrasound analysis in discriminating alpha-decay background events from single nuclear recoils has been confirmed, with a lower bound of $&gt;99.3%$ rejection of alpha-decay events. Twenty single nuclear recoil event candidates and three multiple bubble events were observed during a total exposure of 553 kg-days distributed over three different bubble nucleation thresholds. The effective exposure for single bubble recoil-like events was 437.4 kg-days. A neutron background internal to the apparatus, of known origin, is estimated to account for five single nuclear recoil events and is consistent with the observed rate of multiple bubble events. The remaining excess of single bubble events exhibits characteristics indicating the presence of an additional background. These data provide new direct detection constraints on WIMP-proton spin-dependent scattering for WIMP masses $&gt;20\text{ }\text{ }\mathrm{GeV}/{\mathrm{c}}^{2}$ and demonstrate significant sensitivity for spin-independent interactions.

Though the mainstream organizational literature has advanced in the last 20 years with the integration of transformational and distributed leadership theories, as well as genuine attempts at comprehensive models, the public sector literature has lagged, especially in utilizing large‐scale empirical studies. This study takes advantage of a very large government data set to test the utility of one of the best known theories, the “full range” leadership theory of Bernard Bass. It addresses three important research questions: How inclusive is Bass’s operational definition of leadership? How much of an impact do Bass’s leadership competencies have on follower satisfaction? Finally, how important is transformational leadership compared to transactional leadership in government settings? The results indicate that Bass’s broad definition of leadership comes quite close to capturing what federal employees perceive to be effective leadership. The relationship between good leadership in an organization and follower satisfaction is also presented as an important outcome in the federal government. Finally, both transactional and transformational leadership are perceived as important in the federal government, although transformational leadership is considered slightly more important even after shifting one important factor, individualized consideration, back to the transactional model.

New results are reported from the operation of the PICO-60 dark matter detector, a bubble chamber filled with 52 kg of C3F8 located in the SNOLAB underground laboratory. As in previous PICO bubble chambers, PICO-60 C3F8 exhibits excellent electron recoil and alpha decay rejection, and the observed multiple-scattering neutron rate indicates a single-scatter neutron background of less than 1 event per month. A blind analysis of an efficiency-corrected 1167-kg-day exposure at a 3.3-keV thermodynamic threshold reveals no single-scattering nuclear recoil candidates, consistent with the predicted background. These results set the most stringent direct-detection constraint to date on the WIMP-proton spin-dependent cross section at 3.4 10 -41 cm 2 for a 30-GeV c -2 WIMP, more than one order of magnitude improvement from previous PICO results.

Hospice care professionals (HCPs) experience a large number of stressors in their work settings. The purpose of this study was to investigate the relationship between self-care, compassion fatigue, burnout, and compassion satisfaction among HCPs. Thirty-seven HCPs were surveyed regarding their levels of compassion satisfaction, compassion fatigue, and burnout. Respondents also reported the types of self-care activities in which they took part. Results indicated a relationship between self-care strategies and lower levels of burnout and compassion fatigue, and higher levels of compassion satisfaction. Several suggestions are offered for continued research and practice in the hospice care field.

We use the Survey of Doctorate Recipients to examine the question of who in US universities is patenting. Because standard methods of estimation are not directly applicable, we use a zero-inflated negative binomial model to estimate the patent equation, using instruments for the number of articles to avoid problems of endogeneity. We also estimate the patent model using the generalized method of moments estimation of count data models with endogenous regressors. We find work context and field to be important predictors of the number of patent applications. We also find patents to be positively and significantly related to the number of publications. This finding is robust to the choice of instruments and method of estimation. The cross-sectional nature of the data preclude an examination of whether a trade-off exists between publishing and patenting, holding individual characteristics constant over time. But the strong cross-sectional correlation that we find does not suggest that commercialization has come at the expense of placing knowledge in the public domain.

Final results are reported from operation of the PICO-60 ${\mathrm{C}}_{3}{\mathrm{F}}_{8}$ dark matter detector, a bubble chamber filled with 52 kg of ${\mathrm{C}}_{3}{\mathrm{F}}_{8}$ located in the SNOLAB underground laboratory. The chamber was operated at thermodynamic thresholds as low as 1.2 keV without loss of stability. A new blind 1404-kg-day exposure at 2.45 keV threshold was acquired with approximately the same expected total background rate as the previous 1167-kg-day exposure at 3.3 keV. This increased exposure is enabled in part by a new optical tracking analysis to better identify events near detector walls, permitting a larger fiducial volume. These results set the most stringent direct-detection constraint to date on the weakly interacting massive particle (WIMP)-proton spin-dependent cross section at $3.2\ifmmode\times\else\texttimes\fi{}1{0}^{\ensuremath{-}41}\text{ }{\mathrm{cm}}^{2}$ for a 25 GeV WIMP, improving on previous PICO results for 3--5 GeV WIMPs by an order of magnitude.

Abstract This study uses Event History methodology to examine factors that may contribute to the instability of joint ventures between U.S. multinationals and foreign companies. Using joint venture contract renegotiation as a proxy for instability, it finds statistically significant support for hypotheses that joint ventures are more unstable when partners start out with uneven shares of equity and when the contracts have been renegotiated before. Contract renegotiation is also more likely in relatively open economies than in countries that impose restrictions on direct investment.