Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Tetrahydropalmatine on the Pharmacokinetics of Probe Drugs for CYP1A2, 2D6 and 3A Isoenzymes in Beagle Dogs

Tetrahydropalmatine (Tet) exhibit multiple pharmacological activities and is used frequently by clinical practitioners. In this study, we evaluate the in vivo effects of single and repeated oral Tet administrations on CYP1A2, 2D6 and 3A activities in six beagle dogs in a randomized, controlled, open‐label, crossover study. A cocktail approach, with dosages of the probe drugs caffeine (3.0 mg/kg), metoprolol (2.33 mg/kg) and midazolam (0.45 mg/kg), was used to measure cytochrome P450 (CYP) metabolic activities. The cocktail was administered orally as a single dose (12 mg/kg) 1 day prior to and 4 days after repeated oral Tet administrations (12 mg/kg three times daily). The probe drugs and their metabolites in plasma were quantified simultaneously by a validated HPLC technique, and non‐compartmental parameters were used to evaluate metabolic variables for assessment of CYP inhibition or induction. Tet had no or minor impact on the pharmacokinetics and metabolism of the probe drugs caffeine and metoprolol, CYP1A2 and CYP2D6 substrates, respectively. However, Tet increased AUC0–24 h and decreased AUCratio(0–24 h) (1‐hydroxymidazolam/midazolam ratio) for midazolam statistically significant, both in single or multiple dosing of Tet, with up to 39 or 57% increase for AUC0–24 h and 29% or 22 decrease for AUCratio(0–24 h), respectively, in line with previous in vitro findings for its CYP3A4 inhibition. The extensive use of Tet and herbal medicines containing Tet makes Tet a candidate for further evaluation of CYP3A‐mediated herb–drug interactions. Copyright © 2016 John Wiley & Sons, Ltd.
Understanding women's interpretations of infant formula advertising.

BACKGROUND Exclusive breastfeeding for 6 months and continued breastfeeding for at least 1 year is recommended by all major health organizations. Whereas 74.6 percent of mothers initiate breastfeeding at birth, exclusivity and duration remain significantly lower than national goals. Empirical evidence suggests that exposure to infant formula marketing contributes to supplementation and premature cessation. The objective of this study was to explore how women interpret infant formula advertising to aid in an understanding of this association. METHODS Four focus groups were structured to include women with similar childbearing experience divided according to reproductive status: preconceptional, pregnant, exclusive breastfeeders, and formula feeders. Facilitators used a prepared protocol to guide discussion of infant formula advertisements. Authors conducted a thematic content analysis with special attention to women's statements about what they believed the advertisements said about how the products related to human milk (superior, inferior, similar) and how they reported reacting to these interpretations. RESULTS Participants reported that the advertisements conveyed an expectation of failure with breastfeeding, and that formula is a solution to fussiness, spitting up, and other normal infant behaviors. Participants reported that the advertisements were confusing in terms of how formula-feeding is superior, inferior or the same as breastfeeding. This confusion was exacerbated by an awareness of distribution by health care practitioners and institutions, suggesting provider endorsement of infant formula. CONCLUSIONS Formula marketing appears to decrease mothers' confidence in their ability to breastfeed, especially when provided by health care practitioners and institutions. Therefore, to be supportive of breastfeeding, perinatal educators and practitioners could be more effective if they did not offer infant formula advertising to mothers.
Extended venous thromboembolism prophylaxis after total hip replacement: a comparison of low-molecular-weight heparin with oral anticoagulant.

BACKGROUND Oral anticoagulants and low-molecular-weight heparin are both recommended for venous thromboembolism prophylaxis after total hip replacement. To date, these regimens have not been compared by means of clinical end points in the extended prophylaxis setting. METHODS We randomly assigned 1279 patients 3 days after total hip replacement surgery to fixed-dose subcutaneous low-molecular-weight heparin (reviparin sodium, 4200 anti-Xa IU) or adjusted-dose oral anticoagulant (international normalized ratio, 2-3; acenocoumarol) for a 6-week period. The primary end point was the failure rate, defined as the combined clinical events of a confirmed symptomatic thromboembolic event, a major hemorrhage, or death. All patients were followed up throughout the study interval. The primary objective was to compare the observed cumulative failure rate in the low-molecular-weight heparin vs oral anticoagulant group. RESULTS In the intent-to-treat population, objectively documented symptomatic thromboembolic events occurred in 15 (2.3%) of 643 patients vs 21 (3.3%) of 636 patients receiving low-molecular-weight heparin or oral anticoagulants, respectively (P =.30; 95% confidence interval for the difference, -0.8% to 2.8%). Major bleeding occurred in 9 (1.4%) of 643 patients vs 35 (5.5%) of 636 patients receiving low-molecular-weight heparin or oral anticoagulants, respectively (P =.001). The failure rate was 24 (3.7%) of 643 patients compared with 53 (8.3%) of 636 patients who received low-molecular-weight heparin or oral anticoagulants (P =.001). CONCLUSIONS A significantly higher benefit-risk ratio was observed for patients undergoing elective hip replacement who received extended out-of-hospital prophylaxis with low-molecular-weight heparin vs acenocoumarol. Low-molecular-weight heparin prophylaxis was at least as effective as oral anticoagulants, but with a marked improvement in safety.
The Economic Relevance of Chief Marketing Officers in Firms’ Top Management Teams

The presence of the Chief Marketing Officer (CMO) in the top management team (TMT) should translate into additional wealth creation for shareholders. Using performance attribution analysis, the authors construct a long-short portfolio that buys (sells) stocks of firms with (without) a CMO in the TMT and find this investment strategy would have earned risk-adjusted excess returns of approximately 3%. Additional analyses suggest the value of having a CMO in the TMT manifests primarily among firms with high operating margin, low asset turnover, high profitability, high R&D intensity and high advertising expenses. The authors conclude that having a CMO in the TMT has a positive impact on shareholder wealth.
A three-disulphide derivative of hen lysozyme. Structure, dynamics and stability.

A three-disulphide derivative of hen egg-white lysozyme was made by selective reduction and carboxymethylation of one of the four original disulphide bridges. N-Terminal sequencing and two-dimensional 1H-n.m. r. spectroscopy revealed that the disulphide bridge linking cysteine residues 6 and 127 had been modified and that the three remaining disulphide bonds were native-like in nature. Analysis of COSY and NOESY spectra indicated that the three-disulphide lysozyme (CM6.127-lysozyme retains the same secondary and tertiary structure as its four-disulphide counterpart; its stability to pH and temperature is, however, dramatically decreased. N.m. r. spectroscopy was used to characterize the thermal folding and unfolding transition of CM6.127-lysozyme. Not only is the transition still a highly co-operative event, but the enthalpy change associated with folding and unfolding resembles that of intact lysozyme when their differences in thermal stability are taken into consideration. The significance of these results in terms of the folding process of lysozyme is discussed. By contrast with authentic lysozyme, CM6.127-lysozyme was found to exist in an unfolded state at pH 2 at room temperature. N.m. r. spectroscopy and c.d. were used to characterize this state. Unlike their homologous relative, alpha-lactalbumin, which exists in a partially folded molten globule state under these conditions, only residual non-native-like structure persists in the acid-unfolded state of CM6.127-lysozyme. These results indicate that the difference in folding behaviour of lysozyme and alpha-lactalbumin cannot be accounted for simply by their differences in thermal stability.
Disposition Effect and Overconfidence in Pakistani Stock Market

In worldwide financial markets, increased trading is a more common observable factor that not goes in favor of the standard of classical economic theory based on rational agents and efficient markets. Previous research suggests that market performance operate the level of overconfidence and disposition effect because these factors shows excessive trading. We built a market-wide panel VAR model to investigate the lead-lag relationship between profitability and turnover and TSLS to check the disposition effect. Our results suggesting that investors are less overconfidence in the stock market of Karachi and disposition is also present in this stock exchange. Holding periods were longer for larger stocks and smaller for less illiquid stocks. Return of the security give effects on buy and sells level such as turnover. Hence we can say that overconfident traders mainly hold losers too long.
Regulatory and necrotic volume increase in boar spermatozoa

Spermatozoa of many species initially respond to hypotonicity as perfect osmometers. Thereafter they undergo a regulatory process resulting in a decrease in cell volume, similar to that reported for somatic cells. Regulatory volume increase (RVI), a complementary process which is assumed to occur following initial shrinkage of sperm volume after exposure to a hypertonic medium, has not yet been described in detail for spermatozoa. In this study, we investigated whether spermatozoa are able to regulate their volume after hypertonic stress and whether this ability is maintained in preserved sperm. Cell volume changes were recorded using electronic cell sizing. Sperm response to the ion channels blockers quinidine, tamoxifen, and dydeoxyforskolin, and to protein kinase/phosphatase inhibitors lavendustin, staurosporine, and vanadate was studied to investigate possible mechanisms of RVI. Annexin V staining was used in combination with propidium iodide to determine whether hypertonic stress may induce apoptosis. Overall protein tyrosine phosphorylation under hypertonic conditions was measured via flow cytometry using antiphosphotyrosine antibody. Spermatozoa exposed to hypertonic stress initially responded with an abundant subpopulation according to the perfect osmometer model and recovered their volume from this shrinkage after 20 min. RVI was inhibited by quinidine and tamoxifen, which indicates the involvement of the important cellular ions sodium and chloride in this process. Volume regulatory ability was essentially maintained during storage of liquid semen. However, the response of the sperm population was heterogeneous. A second population raised, containing spermatozoa with larger volumes, which demonstrated irregularities in the volume response with respect to osmotic challenge, ion channel blockers, and storage. Under hypertonic conditions, both protein kinase inhibitors (PKI) led to increased isotonic volumes and to elevated initial relative volumes and subsequent volume decrease. RVI was inhibited by the vanadate. Hypertonic stress did not result in an increase in early apoptotic cells, but produced a shift toward late necrotic cells. Substitution of sodium and chloride by choline and sulfate resulted in decreased isotonic volume of sperm treated with lavendustin. Tyrosine phosphorylation levels were reduced after 20 min under hypertonic conditions. It was concluded that RVI is regulated via a protein tyrosine kinase‐dependent pathway, and that dephosphorylation occurs when volume regulation is required. The necrotic volume increase (NVI) is associated with the accumulation of sodium and chloride following uncontrolled opening of the channels. The ability to regulate volume after exposure to hypertonic conditions is important for sperm functionality and can have practical applications in spermatological diagnostics and cryopreservation. © 2005 Wiley‐Liss, Inc.
Sourcing strategies of U.S. service companies : A modified transaction-cost analysis

Global procurement of services has been receiving an increasing amount of managerial attention in recent years. Service firms seem to have begun sourcing part of their service activities from abroad in much the same way as manufacturing firms have sourced components and finished goods in the past 30 years. However, little is known about the nature of service sourcing strategy. In this study, we employ a modified transaction–cost analysis to examine empirically the locational (domestic vs. global sourcing) and the ownership (internal vs. external sourcing) aspects of service sourcing strategy. In addition, performance implications on both the locational and ownership aspects of service sourcing are investigated. The results show that, similar to components and finished goods procurement, supplementary services are sourced globally, either internally or externally. Furthermore, the relationship between asset specificity and internal sourcing of supplementary services is moderated by the level of inseparability and transaction frequency. Finally, internal sourcing and foreign sourcing of supplementary services are negatively related to a service’s market performance. Copyright © 1999 John Wiley & Sons, Ltd.
Overweight in childhood and adolescence: Does it lead to airway hyperresponsiveness in adulthood?

ABSTRACT Background: Obesity is increasing worldwide among children and adolescents, and has been associated with an increased incidence of asthma. However, the mechanisms underlying this association are incompletely understood. Objective: In this cohort study we aimed to investigate whether being overweight in childhood and adolescence is associated with an increased risk of airway hyperresponsiveness (AHR), a hallmark of asthma, in early adulthood. Methods: Of 527 subjects from a random population sample of children and adolescents (7–17 years) examined at baseline, a total of 184 subjects completed the follow-up visit 20 years later and were included in the present analysis. Both visits included assessment of height and weight, case history and spirometry. At both visits, bronchial provocation tests were performed using either histamine (baseline) or methacholine (follow-up). In addition, fractional exhaled nitric oxide (FeNO) was measured at follow-up. Results: No significant difference in the prevalence of AHR at follow-up was found between subjects who were overweight or obese at baseline visit (n = 26) (pediatric definition, body mass index ≥ 85%percentile) and normal weight subjects (n = 158) (positive bronchial provocation tests: 15.4% vs. 22.2%, respectively, p = 0.35). Likewise, follow-up FeNO levels did not differ significantly between subjects who were lean and those who were overweight or obese at baseline (geometric mean (95% confidence interval [CI]) 15.1 (13.7, 16.6) parts per billion (ppb) versus 13.0 (10.6, 15.9) ppb, p = 0.23). Conclusion: In children and adolescents, being obese or overweight seems not to be associated with an increased risk of AHR or increased FeNO levels in early adulthood.
Empirical investigation of the acceptance and intended use of mobile commerce: location, personal privacy and trust

Mobile commerce (m-commerce) has expanded the scope of service for customers and businesses, alike, enabling customers to shop any time and from any place and businesses to customize their products and services based on the current location of the customer. Consideration must be given to the implications of privacy and trust in m-commerce if utilization and mutual benefit is to be derived on a lasting basis. This research project addresses the factors involved in determining the behavioral intentions of customers toward acceptance and use of m-commerce. Specifically, the study examines the influence of trust on behavioral intent and specifies a model for the acceptance and use of m-commerce. The model developed in this study is an extension of the Unified Theory of Acceptance and Use of Technology (UTAUT) model developed by Venkatesh et al. Trust is added to the model as a determinant of behavioral intent. The research instrument consists of a 50-element questionnaire created in this research project to measure the determinants of trust and other factors related to the acceptance and use of m-commerce. Following three pretests, factor analysis reveals all constructs in the final instrument meet a minimum acceptability level of 0.6. A total of 323 business students comprise the sample pool for this study. ANOVA is used to identify differences in experience levels due to gender, age, and education level. Differences regarding individual privacy sensitivity are also measured. SEM is used to test a baseline model consisting of the components identified in the UTAUT model, which explains 82% of the total variance in m-commerce acceptance. Adding the trust factors to the baseline model increases the explanation value to 84%. Four components of trust (location disclosure, opportunistic behavior, privacy policies and unsolicited messages) are tested and found to be significant. The influence of gender, age, experience level, and privacy sensitivity on trust is accomplished by segmenting the total sample into categories for analysis. Results reveal lack of support for the moderating effect of gender and support for the moderating effect of privacy sensitivity. The moderating effects of age and experience could not be fully tested.
Enhancing Relationships Within Groups: The Impact of Role Perceptions Within Logistics Teams

ABSTRACT Ten years ago, researchers in 2 separate domains called for closer examination of relationship theories: 1st in relationship marketing (D. Bejou, 1997) and 2nd in the dynamics within logistics teams (D. R. Deeter-Schmelz, 1997). Although the extant literature in relationship marketing has emerged rich in empirical and conceptual grounding, little empirical progress has been made with respect to understanding relationships among logistical team members. To that end, our study explores logistics teams and the impact that role perceptions have on their perceived functioning. In particular, the impact of role clarity on logistical team members' perceptions of effectiveness and exchange dynamics is investigated. Results of this study reveal significant differences across team role clarity levels with respect to perceived relationship effectiveness, communication quality, and communication effectiveness. Although most relationship marketing theories have been examined within the company–consumer linkage, opportunities exist for gaining insights by applying these relationship theories in intraorganizational settings.
Uninformed Trading and Information Uncertainty in the Post-IPO Market

Underpricing in the initial public offering (IPO) market has been traditionally explained as a means of attracting liquidity traders. We find strong evidence suggesting that the intensity of trading coming from these uninformed traders and the rate of idiosyncratic information arrival play important roles in determining the level of adverse selection cost of trading in the post-IPO market. Timeseries analysis reveals that this cost is lowest immediately post-IPO and it increases monotonically in the first 8–12 weeks of secondary market trading. Order flow variability and the fraction of small trades (both proxies for the extent of uninformed trading) are at their highest in the immediate aftermarket and their levels decay for the next 8–12 weeks. Our results allude to the existence of a negative relationship between underpricing and the adverse selection problem in the post-IPO market, mediated by the intensity of uninformed trading.
Fear-Avoidance Beliefs, Catastrophizing, and Distress: A Longitudinal Subgroup Analysis on Patients With Musculoskeletal Pain

PurposeThe aim of the present study was to describe fear-avoidance beliefs, catastrophizing, and emotional distress among musculoskeletal pain patients in primary healthcare and to explore the relationship of psychological risk profiles for pain, function, and sick leave from baseline through 1-year and 3-year follow-ups. MethodsRatings from 110 musculoskeletal pain patients were collected and cluster analysis was used to identify subgroups with similar patterns on fear-avoidance beliefs, catastrophizing, and emotional distress. The clusters were examined cross-sectionally and prospectively on sick leave, function, and pain. ResultsFive distinct profiles were found: “low scores cluster,” “high score cluster,” “fear-avoidance beliefs and catastrophizing cluster,” “distress only cluster,” and “medium catastrophizing cluster. ” The “low scores cluster” and “distress only cluster” had the most favorable scores on outcome variables. The analysis of common developmental pathways showed considerable stability over time. Reorganization of clusters in a psychological “high risk cluster” and a “low risk cluster” showed significant differences at 1-year and 3-year follow-ups in functional ability as well as in decreased sick leave. There were no significant differences between the groups on average pain ratings at the 2 measure points. ConclusionsDistinct profiles of catastrophizing, fear-avoidance beliefs, and emotional distress were extracted and meaningfully related to future sick leave and dysfunction outcomes. The structures of the profiles were essentially stable and became more accentuated across a 3-year period. The results underscore the need to address psychological aspects as fear-avoidance beliefs, catastrophizing, and emotional distress in the management of patients with musculoskeletal pain and may open the path for a better tailored treatment approach for this patient group.
Synchronization Error in QAM-Based FBMC System

We investigate the impact of the time offset (TO) and carrier frequency offset (CFO) on the performance of a filter bank multicarrier - quadrature amplitude modulation (FBMC-QAM) system. As opposed to conventional FBMC system where offset QAM (OQAM) is utilized due to the intrinsic interference, the FBMC-QAM system cancels the intrinsic interference based on the orthogonality conditions between the two kinds of filters. Because the FBMC-QAM system uses two kinds of filters, the effects on the TO and CFO are different compared to the conventional FBMC system. The performance of this system is degraded by TO because the two-filter orthogonality conditions are not satisfied, resulting in severe inter-symbol interference (ISI). With respect to the CFO, the orthogonality between the two filters protects from performance degradation caused by intercarrier interference (ICI). Numerical results show that FBMCQAM is more robust against CFO while it is more sensitive to TO compared to the FBMC-OQAM system.