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Irinotecan (CPT-11), a first-line chemotherapy for advanced colorectal cancer, causes serious diarrhea in patients receiving treatment. The underlying mechanism has been shown that the active metabolite of CPT-11, SN-38, is metabolized to the inactive metabolite SN-38 glucuronide (SN-38 G) during hepatic glucuronidation, and subsequently is exported into the intestine, where SN-38 G is hydrolyzed by bacterial β-glucuronidase (βG) to be SN-38, thus leading to intestinal toxicity. Thus, inhibition of the intestinal bacterial βG activity is expected to prevent CPT-11-induced diarrhea. However, the effects of such inhibition on serum pharmacokinetics of SN-38, the key determinant of CPT-11 treatment, are uncertain. Here, we determined the effects of a potent E. coli βG (eβG)-specific inhibitor pyrazolo[4,3-c]quinoline derivative (TCH-3562) for the potential use in preventing CPT-11-induced diarrhea. TCH-3562 exhibited efficacious inhibitory potency of endogenous βG activity in two anaerobes, Eubacteriumsp. and Peptostreptococcus anaerobius. Oral administration of TCH-3562 also effectively reduced the bacterial βG activity in mice intestine. Moreover, pharmacokinetic analysis of TCH-3562 revealed a relatively low amount of TCH-3562 was detected in the plasma whereas the majority of TCH-3562 was found in the feces. Importantly, co-treatment of CPT-11 and TCH-3562 did not decrease active SN-38 level in mice plasma. Finally, we established that TCH-3562 as an adjuvant treatment showed protective effects on CPT-11-induced diarrhea and had no negative effects on the therapeutic efficacy of CPT-11 in tumor-bearing mice. Therefore, inhibition of the intestinal bacterial βG activity by the specific inhibitor, TCH-3562, is promising to prevent CPT-11-induced diarrhea while maintaining its anti-tumor efficacy that may have clinical potentials for the treatment with CPT-11.

The aim of the study was to evaluate changes in late-luteal appetite for highly sweet (HS) and highly salty and fatty (HSF) foods in women with premenstrual dysphoric disorder (PMDD). After initial assessment in a psychiatric interview, the premenstrual symptoms screening tool (PSST) was used to identify women with moderate-to-severe premenstrual symptoms. Sixty-seven women with PMDD and 74 healthy controls were evaluated in the early-follicular and late-luteal (pre-menstrual) phases of the menstrual cycle. Because the PSST is designed to assess symptoms only in the late-luteal phase, an 11-point Likert scale was used to rate PMDD symptoms once a week in the evaluation mentioned previously and the following two menstrual cycles. Participants were shown pictures of 15 highly sweet (HS) and 15 highly salty and fatty (HSF) foods, desire to eat each food was rated on an eleven-point Likert scale (0, "none at all"; 10, "extreme desire"), and sweet-food craving was rated using the food craving-state questionnaire. Emotional responses to the foods were measured with a four-point Likert scale we previously validated. Depression, irritability, and impulsivity were measured with standard psychiatric instruments. Women with PMDD, but not control women, had late-luteal phase elevations in desire to eat HS food, sweet-food craving and emotional responses to HS foods. Desire to eat for HSF foods did not differ significantly across the menstrual cycle between groups. There were significant correlations between emotional responses to and desire to eat HS foods. Moreover, late-luteal phase irritability and impulsivity scores were associated with desire to eat HS foods. These data suggest that targeted assessment of increased late-luteal appetites for HS foods may facilitate clinical interventions in women with PMDD.

Acquirers facing strong union power tend to acquire target firms with cash rather than equity or a mix of cash and equity. A one standard deviation increase in the union power faced by the acquirer increases the odds of choosing cash payment by a factor ranging from 1.26 to 1.57. The effect is stronger when: the acquiring firm is located in states without the right-to-work laws; the interests of managers are more aligned with shareholders in acquiring firms; and acquiring firms’ asset specificity is high. When union power is strong, acquirers making cash payment are associated with a significantly positive announcement return. In addition, they are less likely to experience labor strikes or declines in operating performance, and more likely to obtain wage concessions in collective bargaining in the post-acquisition period than acquirers using other methods of payment. These findings suggest that cash payment allows acquirers to reduce excess liquidity and strengthen their bargaining power with unions.

This study investigates the relations between corporate governance structures, level of diversification, and excess value of the U.S. banks for 2003–2008. Our analysis produces several major findings. First, diversified banks are different from specialized banks in their board structure, monitoring function of audit committee, and the level of antitakeover provisions. Second, governance mechanisms are associated with bank diversification: as the level of diversification increases, board independence, institutional ownership, and managerial entrenchment decrease whereas the ratio of certified inside board directors significantly increases. Our results show that governance structure—particularly the leadership structure, the ratio of certified inside directors on the board, and the level of managerial entrenchment—plays an important role in determining the excess value of diversified banks. The findings provide some insights for bank policymakers, including the proper design or regulation of bank governance structures, which is critical to bank performance because regulation is no longer a substitute for bank governance.

It is more challenging to design peptide drugs than small molecules through molecular docking and in silico analysis. Here, we developed a structure-based approach with various computational and analytical techniques to optimize cancer-targeting peptides for molecular imaging and therapy. We first utilized a peptide-binding protein database to identify GRP78, a specific cancer cell-surface marker, as a target protein for the lead, L-peptide. Subsequently, we used homologous modeling and molecular docking to identify a peptide-binding domain within GRP78 and optimized a series of peptides with a new protein-ligand scoring program, HotLig. Binding of these peptides to GRP78 was confirmed using an oriented immobilization technique for the Biacore system. We further examined the ability of the peptides to target cancer cells through in vitro binding studies with cell lines and clinical cancer specimens, and in vivo tumor imaging and targeted chemotherapeutic studies. MicroSPECT/CT imaging revealed significantly greater uptake of (188)Re-liposomes linked to these peptides as compared with non-targeting (188)Re-liposomes. Conjugation with these peptides also significantly increased the therapeutic efficacy of Lipo-Dox. Notably, peptide-conjugated Lipo-Dox significantly reduced stem-cell subpopulation in xenografts of breast cancer. The structure-based optimization strategy for peptides described here may be useful for developing peptide drugs for cancer imaging and therapy.

A new architecture of a pentaplexer transceiver module which can be used in GPON/GEPON and RFoG triple play optical networks with supporting of the multiple optical wavelengths of 1310 nm, 1490 nm, 1550 nm, 1610 nm, and 1650 nm, is proposed. By using diffractive grating elements combing with market readily available GRIN (Gradient-Index) lens, grating, mirrors, beamsplitter, LDs (Laser Diodes), and PDs (Photodetectors), the proposed design have the advantages of low cost, high efficiency/performance, easy design and manufacturing, over the contemporary triplex transceivers which are made of multilayer filters or waveguides that increase the complexity of manufacturing and reduce the performance efficiency. With the proposed design, a pentaplexer system can accommodate GPON/GEPON, RFoG, and monitoring integration services, total five optical wavelength channels into a hybrid-integrated TO-CAN package platform with sufficient efficiency.

A novel autostereoscopic display system with the characteristics of variable viewing distance control, real-time 2D/3D switchable display, and adjustable lens pitch using an acousto-optic lens (AOL) is proposed. With the unique property of an AOL array, the proposed system can provide viewers to select suitable viewing distances by adjusting the acoustic signal that is applied to the AOL array. With the same property, the system can also be adjusted with an appropriate interpupillary distance (IPD) for personal entertainment applications. The proposed system with adjustable lens pitch, can adopt to different display panels with various resolutions and/or composited images. The operation principle of the system is analyzed with a set of design parameters and a set of simulation results to facilitate the implementation of the system and to verify the validity of the approach.

This paper investigates whether firms’ pollution records influence their financing costs. Evidence shows that lending banks demand significantly higher loan spreads, higher total borrowing costs, shorter loan maturities, smaller loan sizes, and greater collateral from firms with higher levels of chemical releases. The costly effects are stronger for firms with higher default risk and weaker corporate governance. Additonal results show that polluting firms face higher future stock volatility. This evidence supports the view that banks consider firms’ chemical releases when they make lending decisions.

This study complements the governance literature by investigating how Taiwan listed firms adjusted their governance structure to cope with the 2008 financial crisis. The results from the principal component analysis (PCA) suggest that there are significant differences in the factor scores, such as Board Power (of the Largest Shareholders), Information Transparency and Related Party Transactions; the changes in a firm's operating performance are associated with the changes in the scores of the governance factors during the financial crisis. The empirical evidence shows that Taiwan's listed firms adopted new governance structures to better cope with the challenges associated with the financial crisis in 2008.

Summary Aim The aim of the study was to develop and validate an instrument to evaluate nurses' knowledge and to understand the obstacles that they encounter when administering resuscitation medications. Background Insufficient knowledge is a major factor in nurses' drug administration errors. Resuscitation involves situations in which doctors issue oral orders, and is inherently highly stressful. Sufficient knowledge is vital for nurses if they are to respond quickly and accurately when administering resuscitation medications. Methods A cross-sectional study was conducted. A questionnaire (20 true-false questions) developed from literature and expert input, and validated by subject experts and one pilot study, was used to evaluate nurses' knowledge of resuscitation medications. Stratified sampling and descriptive statistics were applied. Results A total of 188 nurses participated. The overall correct answer rate was 70.5% and the greater the nurse's work experience the higher the score. Only 8% of nurses considered themselves to have sufficient knowledge and 73.9% hoped to gain more training about resuscitation medications. The leading obstacle reported was “interruption of the drug administration procedure on resuscitation” (62.8%). Seventeen out of 20 questions achieved a discriminatory power of over 0.36, indicating good to excellent questions. In the study, a total of 16 resuscitation medication errors were reported by the participants, in which the errors involved atropine (five cases), epinephrine (three cases) and others (eight cases). The errors mainly involved misinterpretation of orders, insufficient knowledge and confusing certain drugs for other look-alike drugs. Conclusion Evidence-based results strongly suggest that nurses have insufficient knowledge and could benefit from longer working experience and additional training about resuscitation medications. Further research to validate the instrument is needed and the education of nurses regarding resuscitation medications is recommended.

Using a Taiwan dataset with restrictive family definitions, we examine the relation between family presence and corporate investment policy. Our analysis centers on two incentives that potentially lead to differences in investment policy between family firms and nonfamily firms: family owners' risk aversion and their real option to invest. Our findings indicate that family firms devote significantly more resources to total investment activity and RD and the investment policy appears to be driven by the significantly stronger relation between total investment and idiosyncratic risk for families with more real options (i.e., investment opportunities). Our robustness tests using IV-3SLS regressions provide further support of the real option argument. Further testing indicates that family firms receive more patents/patent citations per RD suggesting that active family control (holding top management position) may explain the higher R&D efficiency associated with family firms. To our knowledge, this paper is the first of its kind to propose the real option argument to explain the relation between family presence and firm investment policy.

This paper empirically examines how labor unions affect investment-cash flow sensitivity using samples from the US covering the period of 1984–2009. We find a significant positive union effect using a q model of investment. The capital expenditures of firms are 1.71 times more sensitive to internal cash flows when unionization rates increase one standard deviation from the mean. This effect holds when we control for other proxies of financial constraints. In addition, unionized firms are associated with lower cash–cash flow sensitivity, which suggests that the higher investment-cash flow sensitivity in unionized firms is primarily driven by the incentive of these firms to reduce liquidity and enhance bargaining power against the union. We also show that the above union effects become more pronounced during labor contract negotiation years.

This study explores the effectiveness of an educational intervention on nurses' knowledge regarding the administration of high-alert medications.Nurses' insufficient knowledge is considered to be one of the most significant factors contributing to medication errors. Most medication errors cause no harm to patients, but the incorrect administration of high-alert medications can result in serious consequences. A previous study by the same authors validated 20 true/false questions concerning high-alert medications and suggested that the topic be taught to nurses (Hsaio, et al., 2010. Nurses' knowledge of high-alert medications: Instrument development and validation. Journal of Advanced Nursing, 66(1), 177-199.).A randomized controlled trial was employed in 2009 in Taiwan. Twenty-one hospital wards and 232 nurses were randomized to control and intervention groups. The sixty-minute educational intervention was based on the viewing of a Powerpoint file developed for this study. The results were compared pre-intervention and six weeks post-intervention by means of a test comprising the 20 questions regarding high-alert medications.The pre-intervention baseline data for correct answer rate was 75.8% (mean; n=232). After the intervention, the post-test showed significant improvement in the intervention group (n=113) (pre vs. post; 77.2±15.5 vs. 94.7±7.6; paired t=10.82, p0.0001) but not in the control group (n=112) (pre vs. post; 74.3±14.7 vs. 75.5±14.2; paired t=0.60; p=0.247).Educational intervention appears to be effective in strengthening nurses' knowledge of high-alert medications. The Powerpoint file presented teaching material which is both suitable and feasible for hospital-based continuing education.

In this paper, we examine how firms react to their competitors’ highly publicized achievements in product innovations. We use the renowned annual R&D 100 Award granted by R&D Magazine since 1965, which has come to be known as the “Oscar of Innovation”, to measure impactful product innovations by rival industry participants. We find that a firm’s propensity to acquire another firm significantly increases following R&D awards won by competitors. A causal interpretation of our finding is supported by the use of the Uniform Trade Secrets Act (UTSA), which exogenously enhances trade secret protection at the state-level, as an instrumental variable. The increase in acquisitiveness driven by innovation envy is stronger for firms with fewer financial constraints, greater technology competition, and more overconfident CEOs.

We examine how various aspects of corporate governance structures affect the capital allocation inefficiency that drives the value discounts of diversified firms. Diversified firms with more effective internal or external governance mechanisms experience more efficient investment allocations at both the firm and segment levels and show less of a diversification discount. The efficiency of the investment allocation process is better for diversified firms with high board independence, low board busyness, high institutional ownership, high outside director ownership, high CEO equity-based pay, high audit quality, and strong shareholder rights. The results hold after controlling for other potential influences. Our evidence suggests that corporate governance considerations are important in assessing the relation between investment efficiency and firm value for diversified firms.

We follow the measurement of Campbell et al. (2011) for managerial optimism and investigate the influences of the different levels of managerial optimism on improving the investment efficiency when firms tend to under-invest or over-invest. The results indicate that an under-invested firm with a CEO that has a high level of managerial optimism can improve the firm's investment efficiency by reducing the degree of underinvestment, further increasing the value of a firm.

Synopsis This paper explores mothering practices and experiences among Southeast Asian women residing in Taiwan. This qualitative study used a series of focus group sessions with photographic documentation to collect information. The transition to motherhood illustrates a dynamics process of gender and international relations and hierarchies. Maternal practices and challenges of these immigrant women were organized into five domains: “A mother is prized because of her son”, “I am a mother, not a paid nanny”, “Raising children, Taiwanese style”, “Shared mothering”, and “Immigrant mothering—More challenges, more promises”. The experiences and adaptation of mothering are mediated by a family's socio-economic situation, the power dynamic within the family, and the support and acceptance received from the dominant society. These findings have important implications for healthcare services and immigration policies.

Various environmental hazards and metals are liberated either into bottom ash or carried away with gases and subsequently trapped in fly ash. Many studies have reported an increase of DNA damage is related to hazardous exposure of municipal waste incinerators. By detecting DNA damage, we compared the DNA migration imposed in workers potentially exposed to hazardous substances, including PCDD/Fs, metals, and silica particles, at a bottom ash recovery plant and fly ash treatment plants in Taiwan. Higher tail moment (TMOM) was found in workers at fly ash treatment plants (7.55) than in the workers in bottom ash plants (2.64), as well as those in blue collar was higher than in white collar workers (5.72 vs. 3.95). Meanwhile, the significantly higher DNA damage was also shown in workers with high integrated exposure score than those with low. The air samplings for particle mass, Cr, and Al concentrations also showed the higher levels in fly ash treatment plants than in the workers in bottom ash plants. Meanwhile, the air samplings inside the two plants suggested that the particle size might be important to affect the workers inhaling the metal into the human body and finally caused to their DNA damage. The data concluded that an elevated DNA damage may be expected in workers at fly ash treatment plants than those at bottom ash plants; however, the occupational hazards in both types of plants, especially at different particle size interval, need more thorough assessment in future studies.

Objective This study compared the risk of adverse pregnancy outcome—including preterm births, low birth weight (LBW), large-gestational-age (LGA), and small-gestational-age (SGA)—among mothers with schizophrenia receiving typical, atypical, and no antipsychotics during pregnancy. They were all compared with control subjects. Methods We used population-based data from the Taiwan National Health Insurance Research Database and birth certificate registry covering the years 2001 to 2003. In total, 696 mothers with schizophrenia and 3480 matched unaffected mothers were included for analysis. After adjusting for characteristics of mother, father, and infants, multivariate logistic regression analyses were performed to examine the risk of LBW, preterm gestation, SGA, and LGA, comparing mothers with schizophrenia and unaffected mothers. Results After adjusting for potential confounders, the odds of LBW and SGA for unaffected mothers respectively were 0.72 (95% CI = 0.50–0.88) and 0.81 (95% CI = 0.64–0.92) times those of mothers with schizophrenia who had not receiving antipsychotics during pregnancy. There was no significant difference in the risk of LBW, preterm births, LGA, and SGA babies compared to mothers with schizophrenia receiving atypical antipsychotics during pregnancy and those not receiving antipsychotics. However, mothers with schizophrenia receiving typical antipsychotics during pregnancy had higher odds of preterm birth (OR = 2.46, 95% CI = 1.50–4.11) compared to those not receiving antipsychotics. Conclusions The data suggest that the risks for LBW and SGA among mothers with schizophrenia are not affected by antipsychotic use. Women who receive treatment with typical antipsychotics during pregnancy are at slightly higher risk of preterm birth.

Objective To evaluate the benefits of the national stroke postacute care (PAC) program on clinical outcomes and subsequent healthcare utilization. Design Propensity score-matched case-control study using the National Health Insurance data. Participants A total of 1480 stroke cases receiving PAC services and 3159 matched controls with similar stroke severity but without PAC services. Measurements Demographic characteristics, functional outcomes (modified Rankin Scale, Barthel Index, Lawton-Brody Instrumental Activities of Daily Living, Functional Oral Intake Scale, Mini-Nutritional Assessment, Berg Balance Test, Usual Gait Speed Test, 6-Minute Walk Test, Fugl-Meyer Assessment (modified sensation and motor), Mini-Mental State Examination, Motor Activity Log, and the Concise Chinese Aphasia Test), subsequent healthcare utilization (90-day stroke re-admission and emergency department visits), and 90-day mortality. Results After propensity score matching, baseline characteristics, stroke severity, and status of healthcare utilization before index stroke admission were similar between cases and controls. After PAC services, the case group obtained significant improvement in all functional domains and may have reduced subsequent disability. Among all functional assessments, balance was the most significantly improved domain and was suggestive for the reduction of subsequent falls risk and related injuries. Compared with controls, patients receiving PAC services had significantly lower 90-day hospital re-admissions [11.1% vs 21.0%, adjusted odds ratio (aOR) 0.47 with 95% confidence interval (CI) 0.34–0.64], stroke-related re-admissions (2.1% vs 8.8%, aOR 0.22, 95% CI 0.12–0.41), and emergency department visits (13.5% vs 24.0%, aOR 0.49, 95% CI 0.37–0.65), but the 90-day mortality rate remained similar between groups (1.4% case group vs 2.0% control group, aOR 0.68, 95% CI 0.29–1.62). Conclusions PAC significantly improved the recovery of stroke patients in all functional domains through the program, with universal interorganizational staff training, periodic functional assessment, and high-intensity rehabilitation. Further longitudinal research is needed to evaluate the long-term survival benefits and healthcare utilization.

Lateral compartmentalization of membrane proteins into microdomains regulates signal transduction; however, structural determinants are incompletely understood. Membrane glycoproteins bind galectins in proportion to the number (i.e. NX(S/T) sites) and degree of GlcNAc branching within attached N-glycans, forming a molecular lattice that negatively regulates T cell function and autoimmunity. We find that in resting T cells, partition of CD45 inside and T cell receptor (TCR)/CD4-Lck/Zap-70 outside microdomains is positively and negatively regulated by the galectin lattice and actin cytoskeleton, respectively. In the absence of TCR ligands, the galectin lattice counteracts F-actin to retain CD45 in microdomains while concurrently blocking TCR/CD4-Lck/Zap-70 partition to microdomains by preventing a conformational change in the TCR that recruits Nck/Wiscott Aldrich Syndrome (WASp)/SLP76/F-actin/CD4 to TCR. The counterbalancing activities of the galectin lattice and actin cytoskeleton negatively and positively regulate Lck activity in resting cells and CD45 versus TCR clustering and signaling at the early immune synapse, respectively. Microdomain-localized CD45 inactivates Lck and inhibits TCR signaling at the early immune synapse. Thus, the galectin lattice and actin cytoskeleton interact on opposing sides of the plasma membrane to control microdomain structure and function, coupling basal growth signaling with thresholds to activation.

The purpose of this study is to investigate the feasibility of developing e-learning and to examine reasons for adopting or rejecting e-learning as an alternative way to conduct continuing education (CE) for public health nurses (PHNs). A nationwide-based cross-sectional study was conducted with a randomly selected sample of 233 PHNs in Taiwan. A structured questionnaire was used to collect data by mailing methods. The majority of PHNs (88.84%, n=207) showed an affirmative intention towards adopting e-learning as their one way of CE. Reasons for adopting e-learning included achieving life learning, fulfilling personal interests, time-saving, based on job needs, information diversity, flexible in time and space, self-regulatory learning, cost-effectiveness, less impact on family duties and life. Twenty-six PHNs (11.16%) who rejected e-learning as their way of CE indicated main reasons including poor computer competence, lack of personal computer and without internet access, heavy work load, heavy family duties, conflict with personal preference, heavy economic burden, lack of motivation, and low self-control. This study reveals a high feasibility of developing e-learning that coexists with other CE models (e.g. traditional instruction). Reasons analyses provide directions for decreasing barriers for developing a learning model of this new medium for nurses' CE.

Autoimmunity is a complex trait disease where the environment influences susceptibility to disease by unclear mechanisms. T cell receptor clustering and signaling at the immune synapse, T cell proliferation, CTLA-4 endocytosis, T(H)1 differentiation, and autoimmunity are negatively regulated by beta1,6GlcNAc-branched N-glycans attached to cell surface glycoproteins. Beta1,6GlcNAc-branched N-glycan expression in T cells is dependent on metabolite supply to UDP-GlcNAc biosynthesis (hexosamine pathway) and in turn to Golgi N-acetylglucosaminyltransferases Mgat1, -2, -4, and -5. In Jurkat T cells, beta1,6GlcNAc-branching in N-glycans is stimulated by metabolites supplying the hexosamine pathway including glucose, GlcNAc, acetoacetate, glutamine, ammonia, or uridine but not by control metabolites mannosamine, galactose, mannose, succinate, or pyruvate. Hexosamine supplementation in vitro and in vivo also increases beta1,6GlcNAc-branched N-glycans in naïve mouse T cells and suppresses T cell receptor signaling, T cell proliferation, CTLA-4 endocytosis, T(H)1 differentiation, experimental autoimmune encephalomyelitis, and autoimmune diabetes in non-obese diabetic mice. Our results indicate that metabolite flux through the hexosamine and N-glycan pathways conditionally regulates autoimmunity by modulating multiple T cell functionalities downstream of beta1,6GlcNAc-branched N-glycans. This suggests metabolic therapy as a potential treatment for autoimmune disease.