bluuebunny/crossref_metadata_2025 huggingface dataset:
C2Maps: a network pharmacology database with comprehensive disease-gene-drug connectivity relationships
Authors: Huang Hui , Wu Xiaogang , Pandey Ragini , Li Jiao , Zhao Guoling , Ibrahim Sara , Chen Jake Y
Published: October 2012

Background

Network pharmacology has emerged as a new topic of study in recent years. It aims to study the myriad relationships among proteins, drugs, and disease phenotypes. The concept of molecular connectivity maps has been proposed to establish comprehensive knowledge links between molecules of interest in a given biological context. Molecular connectivity maps between drugs and genes/proteins in specific disease contexts can be particularly valuable, since the functional approach with these maps helps researchers gain global perspectives on both the therapeutic profiles and toxicological profiles of candidate drugs.

Methods

To assess drug pharmacological effect, we assume that "ideal" drugs for a patient can treat or prevent the disease by modulating gene expression profiles of this patient to the similar level with those in healthy people. Starting from this hypothesis, we build comprehensive disease-gene-drug connectivity relationships with drug-protein directionality (inhibit/activate) information based on a computational connectivity maps (C2Maps) platform. An interactive interface for directionality annotation of drug-protein pairs with literature evidences from PubMed has been added to the new version of C2Maps. We also upload the curated directionality information of drug-protein pairs specific for three complex diseases - breast cancer, colorectal cancer and Alzheimer disease.

Results

For relevant drug-protein pairs with directionality information, we use breast cancer as a case study to demonstrate the functionality of disease-specific searching. Based on the results obtained from searching, we perform pharmacological effect evaluation for two important breast cancer drugs on treating patients diagnosed with different breast cancer subtypes. The evaluation is performed on a well-studied breast cancer gene expression microarray dataset to portray how useful the updated C2Maps is in assessing drug efficacy and toxicity information.

Conclusions

The C2Maps platform is an online bioinformatics resource that provides biologists with directional relationships between drugs and genes/proteins in specific disease contexts based on network mining, literature mining, and drug effect annotating. A new insight to assess overall drug efficacy and toxicity can be provided by using the C2Maps platform to identify disease relevant proteins and drugs. The case study on breast cancer correlates very well with the existing pharmacology of the two breast cancer drugs and highlights the significance of C2Maps database.
Application of binding pancreatogastrostomy in laparoscopic central pancreatectomy
Authors: Defei Hong , Ying Xin , Xiujun Cai , Shuyou Peng
Published: October 2012

Background

The feasibility of binding pancreaticogastrostomy in laparoscopic central pancreatectomy is not known.

Methods

In October 2011, a female patient with a pancreatic neck mass received laparoscopic central pancreatectomy with binding pancreaticogastrostomy.

Results

The operation was successful. No complications occurred. The operative time was 210 min. Blood loss was 120 ml. On day 11 after the operation, the patient was discharged. The postoperative pathological result showed a 2 × 2 × 2-cm solid pseudopapillary tumor of the pancreas with intrapancreatic infiltration. The surgical margin was negative.

Conclusions

Laparoscopic central pancreatectomy with binding pancreaticogastrostomy might be feasible, facilitating further study in laparoscopic pancreatoduodenectomy.

Trial registration

This study was waived from trial registration because it is a retrospective analysis of medical records.
Prolonged sedentary time and physical activity in workplace and non-work contexts: a cross-sectional study of office, customer service and call centre employees
Authors: Thorp Alicia A , Healy Genevieve N , Winkler Elisabeth , Clark Bronwyn K , Gardiner Paul A , Owen Neville , Dunstan David W
Published: October 2012

Background

To examine sedentary time, prolonged sedentary bouts and physical activity in Australian employees from different workplace settings, within work and non-work contexts.

Methods

A convenience sample of 193 employees working in offices (131), call centres (36) and customer service (26) was recruited. Actigraph GT1M accelerometers were used to derive percentages of time spent sedentary (<100 counts per minute; cpm), in prolonged sedentary bouts (≥20 minutes or ≥30 minutes), light-intensity activity (100–1951 cpm) and moderate-to-vigorous physical activity (MVPA; ≥1952 cpm). Using mixed models adjusted for confounders, these were compared for: work days versus non-work days; work hours versus non-work hours (work days only); and, across workplace settings.

Results

Working hours were mostly spent sedentary (77.0%, 95%CI: 76.3, 77.6), with approximately half of this time accumulated in prolonged bouts of 20 minutes or more. There were significant (p<0.05) differences in all outcomes between workdays and non-work days, and, on workdays, between work- versus non-work hours. Results consistently showed “work” was more sedentary and had less light-intensity activity, than “non-work”. The period immediately after work appeared important for MVPA. There were significant (p<0.05) differences in all sedentary and activity outcomes occurring during work hours across the workplace settings. Call-centre workers were generally the most sedentary and least physically active at work; customer service workers were typically the least sedentary and the most active at work.

Conclusion

The workplace is a key setting for prolonged sedentary time, especially for some occupational groups, and the potential health risk burden attached requires investigation. Future workplace regulations and health promotion initiatives for sedentary occupations to reduce prolonged sitting time should be considered.
Fast responsive, optical trace level ammonia sensor for environmental monitoring
Authors: Abel Tobias , Ungerböck Birgit , Klimant Ingo , Mayr Torsten
Published: October 2012

Background

Ammonia is a ubiquitous chemical substance which is created in technical and biological processes and harmful to many different organisms. One specific problem is the toxicity of ammonia in fish at levels of 25 μg/l - a very common issue in today’s aqua culture. In this study we report a development of a fast responsive, optical ammonia sensor for trace concentrations.

Results

Different hydrogels have been investigated as host polymers for a pH based sensing mechanism based on fluorescent dyes. A porous hydrophobic fluoropolymer membrane was used as an ion barrier cover layer to achieve a good ammonia permeability. The sensor’s sensitivity towards ammonia as well as crosssensitivity towards pH-value and salinity, and the temperature dependency have been determined. Two different methods to reference fluorescence signals have been employed to eliminate intensity-based measurement drawbacks.

Conclusion

The presented sensor features high sensitivity and a fast response even at concentrations near 1 ppb. No cross sensitivity towards pH and salinity could be observed and temperature dependency was determined as compensateable. Both referencing approaches prove themselves to be able to provide a simple use of the sensor for in-field applications.
Production of four Neurospora crassa lytic polysaccharide monooxygenases in Pichia pastoris monitored by a fluorimetric assay
Authors: Kittl Roman , Kracher Daniel , Burgstaller Daniel , Haltrich Dietmar , Ludwig Roland
Published: October 2012

Background

Recent studies demonstrate that enzymes from the glycosyl hydrolase family 61 (GH61) show lytic polysaccharide monooxygenase (PMO) activity. Together with cellobiose dehydrogenase (CDH) an enzymatic system capable of oxidative cellulose cleavage is formed, which increases the efficiency of cellulases and put PMOs at focus of biofuel research. Large amounts of purified PMOs, which are difficult to obtain from the native fungal producers, are needed to study their reaction kinetics, structure and industrial application. In addition, a fast and robust enzymatic assay is necessary to monitor enzyme production and purification.

Results

Four pmo genes from Neurospora crassa were expressed in P. pastoris under control of the AOX1 promoter. High yields were obtained for the glycosylated gene products PMO-01867, PMO-02916 and PMO-08760 (>300 mg L-1), whereas the yield of non-glycosylated PMO-03328 was moderate (~45 mg L-1). The production and purification of all four enzymes was specifically followed by a newly developed, fast assay based on a side reaction of PMO: the production of H2O2 in the presence of reductants. While ascorbate is a suitable reductant for homogeneous PMO preparations, fermentation samples require the specific electron donor CDH.

Conclusions

P. pastoris is a high performing expression host for N. crassa PMOs. The pmo genes under control of the native signal sequence are correctly processed and active. The novel CDH-based enzyme assay allows fast determination of PMO activity in fermentation samples and is robust against interfering matrix components.
Mucin (Muc) expression during pancreatic cancer progression in spontaneous mouse model: potential implications for diagnosis and therapy
Authors: Rachagani Satyanarayana , Torres María P , Kumar Sushil , Haridas Dhanya , Baine Michael , Macha Muzafar A , Kaur Sukhwinder , Ponnusamy Moorthy P , Dey Parama , Seshacharyulu Parthasarathy , Johansson Sonny L , Jain Maneesh , Wagner Kay-Uwe , Batra Surinder K
Published: October 2012

Background

Pancreatic cancer (PC) is a lethal malignancy primarily driven by activated Kras mutations and characterized by the deregulation of several genes including mucins. Previous studies on mucins have identified their significant role in both benign and malignant human diseases including PC progression and metastasis. However, the initiation of MUC expression during PC remains unknown because of lack of early stage tumor tissues from PC patients.

Methods

In the present study, we have evaluated stage specific expression patterns of mucins during mouse PC progression in (KrasG12D;Pdx1-Cre (KC)) murine PC model from pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDAC) by immunohistochemistry and quantitative real-time PCR.

Results

In agreement with previous studies on human PC, we observed a progressive increase in the expression of mucins particularly Muc1, Muc4 and Muc5AC in the pancreas of KC (as early as PanIN I) mice with advancement of PanIN lesions and PDAC both at mRNA and protein levels. Additionally, mucin expression correlated with the increased expression of inflammatory cytokines IFN-γ (p < 0.0062), CXCL1 (p < 0.00014) and CXCL2 (p < 0.08) in the pancreas of KC mice, which are known to induce mucin expression. Further, we also observed progressive increase in inflammation in pancreas of KC mice from 10 to 50 weeks of age as indicated by the increase in the macrophage infiltration. Overall, this study corroborates with previous human studies that indicated the aberrant overexpression of MUC1, MUC4 and MUC5AC mucins during the progression of PC.

Conclusions

Our study reinforces the potential utility of the KC murine model for determining the functional role of mucins in PC pathogenesis by crossing KC mice with corresponding mucin knockout mice and evaluating mucin based diagnostic and therapeutic approaches for lethal PC.
p130Cas/Cyclooxygenase-2 axis in the control of mesenchymal plasticity of breast cancer cells
Authors: Bisaro Brigitte , Montani Maura , Konstantinidou Georgia , Marchini Cristina , Pietrella Lucia , Iezzi Manuela , Galiè Mirco , Orso Francesca , Camporeale Annalisa , Colombo Shana M , Di Stefano Paola , Tornillo Giusy , Camacho-Leal Maria P , Turco Emilia , Taverna Daniela , Cabodi Sara , Amici Augusto , Defilippi Paola
Published: October 2012

Introduction

Intrinsic plasticity of breast carcinoma cells allows them to undergo a transient and reversible conversion into mesenchymal cells to disseminate into distant organs, where they can re-differentiate to an epithelial-like status to form a cohesive secondary mass. The p130Cas scaffold protein is overexpressed in human ER+ and HER2+ breast cancer where it contributes to cancer progression, invasion and resistance to therapy. However, its role in regulating mesenchymal aggressive breast cancer cells remains to be determined. The aim of this study was to investigate the molecular and functional involvement of this adaptor protein in breast cancer cell plasticity.

Methods

We used silencing strategies and rescue experiments to evaluate phenotypic and biochemical changes from mesenchymal to epithelial traits in breast tumor cell lines. In the mouse A17 cell model previously related to mesenchymal cancer stem cells and basal-like breast cancer, we biochemically dissected the signaling pathways involved and performed functional in vivo tumor growth ability assays. The significance of the signaling platform was assessed in a human setting through the use of specific inhibitors in aggressive MDA-MB-231 subpopulation LM2-4175 cells. To evaluate the clinical relevance of the results, we analyzed publicly available microarray data from the Netherlands Cancer Institute and from the Koo Foundation Sun Yat-Sen Cancer Center.

Results

We show that p130Cas silencing induces loss of mesenchymal features, by downregulating Vimentin, Snail, Slug and Twist transcriptional factors, resulting in the acquirement of epithelial-like traits. Mechanistically, p130Cas controls Cyclooxygenase-2 transcriptional expression, which in turn contributes to p130Cas-dependent maintenance of mesenchymal phenotype. This cascade of events also compromises in vivo tumor growth through inhibition of cell signaling controlling cell cycle progression. c-Src and JNK kinases are sequential players in p130Cas/ Cyclooxygenase-2 axis and their pharmacological inhibition is sufficient to downregulate Cyclooxygenase-2 leading to an epithelial phenotype. Finally, in silico microarray data analysis indicates that p130Cas and Cyclooxygenase-2 concomitant overexpression predicts poor survival and high probability of breast tumor recurrence.

Conclusions

Overall, these data identify a new p130Cas/Cyclooxygenase-2 axis as a crucial element in the control of breast tumor plasticity, opening new therapeutic strategies leading to inhibition of these pathways in aggressive breast carcinoma.
Aberrations in translational regulation are associated with poor prognosis in hormone receptor-positive breast cancer
Authors: Meric-Bernstam Funda , Chen Huiqin , Akcakanat Argun , Do Kim-Anh , Lluch Ana , Hennessy Bryan T , Hortobagyi Gabriel N , Mills Gordon B , Gonzalez-Angulo Ana Maria
Published: October 2012

Introduction

Translation initiation is activated in cancer through increase in eukaryotic initiation factor 4E (eIF4E), eIF4G, phosphorylated eIF4E-binding protein (p4E-BP1) and phosphorylated ribosomal protein S6 (pS6), and decreased programmed cell death protein 4 (pdcd4), a translational inhibitor. Further, translation elongation is deregulated though alterations in eukaryotic elongation factor 2 (eEF2) and eEF2 kinase (eEF2K). We sought to determine the association of these translational aberrations with clinical-pathologic factors and survival outcomes in hormone receptor-positive breast cancer.

Methods

Primary tumors were collected from 190 patients with Stage I to III hormone receptor-positive breast cancer. Expression of eIF4E, eIF4G, 4E-BP1, p4E-BP1 T37/46, p4E-BP1 S65, p4E-BP1 T70, S6, pS6 S235/236, pS6 S240/244, pdcd4, eEF2 and eEF2K was assessed by reverse phase protein arrays. Univariable and multivariable analyses for recurrence-free survival (RFS) and overall survival (OS) were performed.

Results

High eEF2, S6, pS6 S240/244, p4E-BP1 T70, and low pdcd4 were significantly associated with node positivity. Median follow-up for living patients was 96 months.

High p4E-BP1 T36/47, p4E-BP1 S65, p4E-BP1 T70 and 4E-BP1 were associated with worse RFS. High p4E-BP1 T70 and pS6 S235/236, and low pdcd4, were associated with worse OS. In multivariable analysis, in addition to positive nodes, p4E-BP1 S65 remained a significant predictor of RFS (HR = 1.62, 95% CI = 1.13-2.31; P = 0.008). In addition to age, pS6 S235/236 (HR = 1.73, 95% CI = 1.03-2.90, P = 0.039), eEF2K (HR = 2.19, 95% CI = 1.35-3.56, P = 0.002) and pdcd4 (HR = 0.42, 95% CI = 0.25-0.70, P = 0.001) were associated with OS.

Conclusions

Increased pS6, p4E-BP1, eEF2K and decreased pdcd4 are associated with poor prognosis in hormone receptor-positive breast cancer, suggesting their role as prognostic markers and therapeutic targets.
Mechanisms underlying ICU muscle wasting and effects of passive mechanical loading
Authors: Llano-Diez Monica , Renaud Guillaume , Andersson Magnus , Marrero Humberto Gonzales , Cacciani Nicola , Engquist Henrik , Corpeño Rebeca , Artemenko Konstantin , Bergquist Jonas , Larsson Lars
Published: October 2012

Introduction

Critically ill ICU patients commonly develop severe muscle wasting and impaired muscle function, leading to delayed recovery, with subsequent increased morbidity and financial costs, and decreased quality of life for survivors. Critical illness myopathy (CIM) is a frequently observed neuromuscular disorder in ICU patients. Sepsis, systemic corticosteroid hormone treatment and post-synaptic neuromuscular blockade have been forwarded as the dominating triggering factors. Recent experimental results from our group using a unique experimental rat ICU model show that the mechanical silencing associated with CIM is the primary triggering factor. This study aims to unravel the mechanisms underlying CIM, and to evaluate the effects of a specific intervention aiming at reducing mechanical silencing in sedated and mechanically ventilated ICU patients.

Methods

Muscle gene/protein expression, post-translational modifications (PTMs), muscle membrane excitability, muscle mass measurements, and contractile properties at the single muscle fiber level were explored in seven deeply sedated and mechanically ventilated ICU patients (not exposed to systemic corticosteroid hormone treatment, post-synaptic neuromuscular blockade or sepsis) subjected to unilateral passive mechanical loading for 10 hours per day (2.5 hours, four times) for 9 ± 1 days.

Results

These patients developed a phenotype considered pathognomonic of CIM; that is, severe muscle wasting and a preferential myosin loss (P < 0.001). In addition, myosin PTMs specific to the ICU condition were observed in parallel with an increased sarcolemmal expression and cytoplasmic translocation of neuronal nitric oxide synthase. Passive mechanical loading for 9 ± 1 days resulted in a 35% higher specific force (P < 0.001) compared with the unloaded leg, although it was not sufficient to prevent the loss of muscle mass.

Conclusion

Mechanical silencing is suggested to be a primary mechanism underlying CIM; that is, triggering the myosin loss, muscle wasting and myosin PTMs. The higher neuronal nitric oxide synthase expression found in the ICU patients and its cytoplasmic translocation are forwarded as a probable mechanism underlying these modifications. The positive effect of passive loading on muscle fiber function strongly supports the importance of early physical therapy and mobilization in deeply sedated and mechanically ventilated ICU patients.
Choice and rejection of psychiatry as a career: surveys of UK medical graduates from 1974 to 2009
Authors: Goldacre Michael J. , Fazel Seena , Smith Fay , Lambert Trevor
Published: October 2012

Background

Recruitment of adequate numbers of doctors to psychiatry is difficult.

Aims

To report on career choice for psychiatry, comparing intending psychiatrists with doctors who chose other clinical careers.

Method

Questionnaire studies of all newly qualified doctors from all UK medical schools in 12 qualification years between 1974 and 2009 (33 974 respondent doctors).

Results

One, three and five years after graduation, 4–5% of doctors specified psychiatry as their first choice of future career. This was largely unchanged across the 35 years. Comparing intending psychiatrists with doctors who chose other careers, factors with a greater influence on psychiatrists' choice included their experience of the subject at medical school, self-appraisal of their own skills, and inclinations before medical school. In a substudy of doctors who initially considered but then did not pursue specialty choices, 72% of those who did not pursue psychiatry gave ‘job content’ as their reason compared with 33% of doctors who considered but did not pursue other specialties. Historically, more women than men have chosen psychiatry, but the gap has closed over the past decade.

Conclusions

Junior doctors' views about psychiatry as a possible career range from high levels of enthusiasm to antipathy, and are more polarised than views about other specialties. Shortening of working hours and improvements to working practices in other hospital-based specialties in the UK may have reduced the relative attractiveness of psychiatry to women doctors. The extent to which views of newly qualified doctors about psychiatry can be modified by medical school education, and by greater exposure to psychiatry during student and early postgraduate years, needs investigation.
Determination of Binding Constants for Inclusion Complexes of Cyclodextrins with Organic Solvents, Ethylene Glycol, and Its Related Compounds by Means of 1H NMR Spectroscopy
Authors: Yoshikiyo Keisuke , Matsui Yoshihisa , Yamamoto Tatsuyuki
Published: October 2012

The binding constants (Ka’s) for the complexation of α- and β-cyclodextrins (α- and β-CDs) with some hydrophilic organic solvents such as methanol, dimethyl sulfoxide, acetone, etc., were successfully determined in D2O by following changes in the 1H NMR chemical shift of the C(3)–H signal of CD, using the C(1)–H signal as an internal reference. The Ka value obtained for a β-CD–methanol complex was 0.088 mol−1 dm3 at 298 K, which is, as we know, the smallest among Ka’s measured thus far for CD complexes. The same method was also applied to the determination of Ka’s for the complexation of α-CD with ethylene glycol and some related compounds. It was revealed that these molecules were certainly included within the cavity of α-CD, though the Ka values are fairly small.
A Useful and Convenient Synthetic Protocol for Iodination of Organic Substrates Using a Combination of Vanadyl Acetylacetonate, Hydrogen Peroxide, and Sodium Iodide
Authors: Khan Abu T , Ali Shahzad
Published: October 2012

A wide variety of organic substrates can be iodinated selectively in good yields by employing a combination of vanadyl acetylacetonate, hydrogen peroxide, and sodium iodide at ice-bath temperature. Good yield, selectivity, use of cost effective reagents, and mild and environmentally benign reaction conditions are some of the major advantages of this protocol.
Synthesis of a Novel Ruthenium Sensitizer Bearing an ortho-Dicarboxyphenyl Group as an Anchoring Unit for Dye-sensitized Solar Cells
Authors: Ozawa Hironobu , Oura Shohei , Shimizu Ryosuke , Arakawa Hironori
Published: October 2012

A novel ruthenium sensitizer TUS-20, which is a structural analog of black dye, bearing an ortho-dicarboxyphenylterpyridine as an anchoring unit to TiO2 surface has been synthesized. Adsorption rate of TUS-20 was much faster, and the maximum amount of dye adsorption was larger than that of black dye. The dye-sensitized solar cell with TUS-20 exhibited 7.3% conversion efficiency under AM 1.5 (100 mW cm−2) irradiation.
Fabrication of Large Porous ZSM-5 Bulk Bodies by a One-pot Hydrothermal Method
Authors: Igi Eisaku , Kameshima Yoshikazu , Nishimoto Shunsuke , Miyake Michihiro
Published: October 2012

The fabrication of large ZSM-5 bulk bodies by a hydrothermal method was investigated. The results reveal that porous ZSM-5 bulk bodies with sizes of the order of centimeters could be prepared by the one-pot hydrothermal method using raw materials for synthesizing ZSM-5 powder. Machinability tests and mechanical strength measurements suggest that the bulk bodies obtained are promising as practical materials.
Gelation of Poly(l-lactic acid) Induced by Complex Crystallization with Solvents
Authors: Matsuda Yasuhiro , Fukatsu Akinobu , Tasaka Shigeru
Published: October 2012

Gels of poly(l-lactic acid) (PLLA) in several solvents, including N,N-dimethylformamide (DMF) were formed by cooling solutions of PLLA. Polarizing optical micrographs showed the formation of spherulites of PLLA in the gels below 70 °C. The storage modulus of the gel decreased abruptly below 70 °C, which suggest that the crystalline structure of PLLA prevented the flow of DMF and induced the gelation. The X-ray diffraction (XRD) patterns of the gels were similar to those of the ε-crystals of PLLA which were induced by the formation of complex crystallization with DMF. The mechanism of the formation of the gel is discussed based on the experimental data.
Formation of Planar Bilayer Membranes on Solid Supports Using Peptide Gemini Surfactants
Authors: Umezaki Katsunari , Sakai Shunsuke , Koeda Shuhei , Yamamoto Yasushi , Kondo Masaharu , Ikeda Atsushi , Dewa Takehisa , Taga Keijiro , Tanaka Toshiki , Mizuno Toshihisa
Published: October 2012

Peptide-based gemini surfactants, called PG-surfactants, consisting of a tri- or tetra-Asp peptide core and acetylated dodecylamine-conjugated Cys residues at both the N- and C-terminal ends (D3C12 and D4C12), form a stable planar bilayer membrane on a solid support. From the DLS and TEM analyses, D3C12 and D4C12 have a tendency to form bilayer morphologies in a buffer solution, which reflects their tendency to form a stable planar bilayer membrane.
Lipschitz Games
Authors: Azrieli Yaron , Shmaya Eran
Published: October 2012

The Lipschitz constant of a finite normal-form game is the maximal change in some player's payoff when a single opponent changes his strategy. We prove that games with small Lipschitz constant admit pure ϵ-equilibria, and pinpoint the maximal Lipschitz constant that is sufficient to imply existence of a pure ϵ-equilibrium as a function of the number of players in the game and the number of strategies of each player. Our proofs use the probabilistic method.
Persistently Optimal Policies in Stochastic Dynamic Programming with Generalized Discounting
Authors: Jaśkiewicz A. , Matkowski J. , Nowak A. S.
Published: October 2012

In this paper we study a Markov decision process with a nonlinear discount function. First, we define a utility on the space of trajectories of the process in the finite and infinite time horizon and then take their expected values. It turns out that the associated optimization problem leads to a nonstationary dynamic programming and an infinite system of Bellman equations, which result in obtaining persistently optimal policies. Our theory is enriched by examples.
Impact of Variety and Distribution System Characteristics on Inventory Levels at U.S. Retailers
Authors: Rajagopalan Sampath
Published: October 2012

Over the past six decades, numerous analytical models have been developed to determine optimal inventory levels. These models predict that inventories carried by a retailer should be a function of the product variety carried by the retailer, distribution system characteristics, economies of scale, etc. A few recent empirical studies have explored the impact of some of these factors on aggregate inventories at U.S. retailers. Building on these works, this study empirically explores the role of key factors such as product variety, number of stores, and number of warehouses in explaining inventory levels at U.S. retailers using data obtained from both primary and secondary sources. We find that variety as measured by the number of stock-keeping units carried and number of stores is associated with higher inventories, whereas scale economies are associated with lower inventories. We do not find the number of warehouses to be significant in explaining inventory levels. Increased demand fluctuations are also associated with higher inventories, although the effects are less robust. The significant variables together with retailer segment identifiers explain a substantial fraction of the variance in inventory levels and can be potentially useful to managers in benchmarking their inventory levels.
Avoiding Inadvertent Intravenous Injection of Oral Liquids; Medication within Intravenous Tubing may be Overlooked; Searching by Drug Name Gives Information on Wrong Drug
Authors: Cohen Michael R. , Smetzer Judy L.
Published: October 2012

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs.

Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below.

Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications.
Which Comes First CPOE or eMAR? A Retrospective Analysis of Health Information Technology Implementation
Authors: Sullins Amanda K. , Richard Ashley A. , Manasco Kalen B. , Phillips Marjorie S. , Gomez Tad A.
Published: October 2012

Purpose

The objective of this study was to determine whether the order of implementation of computerized prescriber order entry (CPOE) and electronic medication administration records (eMAR) into a health care facility would impact the medication error rate at an academic medical center.

Methods

A single academic medical center implemented CPOE first in one of its facilities (CPOE-first facility) and eMAR first in the other facility (eMAR-first facility). We conducted a retrospective chart review of patients admitted during designated data collection time periods (baseline, after the first intervention, and after both CPOE and eMAR). The primary outcome was defined as the change in medication error rate from baseline to the first intervention (either CPOE or eMAR). Secondary aims included evaluating final medication error rate and the severity and origin of detected errors.

Results

In the eMAR-first facility, the medication error rate decreased by 22.6% from baseline after only eMAR was introduced (odds ratio [OR], 1.4; P < .05). The CPOE-first facility showed a 13.3% reduction in the medication error rate after only CPOE was introduced (OR, 1.18; P = .24). Both hospitals demonstrated a significant decrease in medication error rates from baseline to after both CPOE and eMAR were implemented. Additionally, eMAR seemed to reduce errors reaching the patient to a greater extent than CPOE.

Conclusion

The integration of eMAR prior to CPOE resulted in a greater reduction in medication errors during the implementation of computerized health care technology. Because eMAR also reduced errors reaching the patient, we recommend initiating health information technology implementation with eMAR prior to CPOE.
Lorcaserin Hydrochloride
Authors: Cada Dennis J. , Levien Terri L. , Baker Danial E.
Published: October 2012

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. Subscribers to The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The November 2012 monograph topics are on vincristine sulfate liposome injection; ZIV-aflibercept; icosapent ethyl; prednisone delayed-release tablets; and elvitegravir, cobicistat, emtricitabine, tenofovir DF. The DUE/MUE is on vincristine sulfate liposome.
Emphasising the European Union's Commitment to Cancer Research: A Helicopter View of the Seventh Framework Programme for Research and Technological Development
Authors: Loo Jan-Willem , Trzaska Dominika , Berkouk Karim , Vidal Maria , Draghia-Akli Ruxandra
Published: October 2012

This article discusses the efforts undertaken in the European Union toward basic, translational, and clinical cancer research on prevention, early diagnosis, prognosis, treatment, cancer control, quality of life, and survivorship.
AKI in a Hospitalized Patient with Cellulitis
Authors: Perazella Mark A.
Published: October 2012

AKI occurs commonly in hospitalized patients with multiple comorbidities. In this Attending Rounds, a woman with AKI in the setting of an infection, use of antibiotics and other medications, bacteremia, and hypotension is considered. Such patients lead to a broad differential diagnosis for AKI including prerenal AKI, acute tubular injury/acute tubular necrosis, infection-related GN, and drug-induced acute interstitial nephritis. The roles of an accurate history, physical examination, laboratory data, and kidney biopsy are highlighted in establishing the correct diagnosis in such patients.
Self-Efficacy of US High School Teachers Teaching the Federal Budget, National Debt and Budget Deficit: A Mixed-Methods Case Study
Authors: Marri Anand R. , Ahn Meesuk , Fletcher Jeffrey , Heng Tang T. , Hatch Thomas
Published: October 2012

This study examined US high school social studies teachers' self-efficacy in teaching the federal budget, national debt and budget deficit prior to and after implementing a pilot curriculum on these topics. The authors examined 24 teachers' topical knowledge, inquiry-based instructional skills in democratic-dialogue-focused lessons and attitudes in civic engagement activities by using baseline and post-self-efficacy surveys, and interviews. The findings revealed that the implemented pilot curriculum had no effect on teachers' confidence of topical knowledge in teaching the topics, while a positive effect was found in the confidence of teachers in facilitating democratic dialogue. Additionally, after using the curriculum, teachers showed an increase in their belief that citizens can make a difference in society. The qualitative data from interviews with the teachers confirmed the survey results, and the teachers' positive perceptions of the curriculum experience suggested an overall success of the curriculum experience for teachers' self-efficacy. The authors believe the findings are suggestive of a process of learning that teachers themselves undertake in mastering content knowledge. An understanding of how teachers confront economic and public policy teaching tools and increases in self-efficacy may result in more empowered teachers and informed students.
Education, Ethics and Religion: A Case Study
Authors: Crawford Keith A.
Published: October 2012

While many nations have abandoned religious proselytising within public schools, within Australia instruction in the doctrine of particular religious faiths is enshrined in laws dating from the late nineteenth century and remains for the majority of children attending primary schools a weekly part of their educational experience. However, recent years have seen a number of initiatives that have called into question the historically privileged hegemonic dominance enjoyed by religious instruction. This article analyses one such challenge – the controversy generated by the introduction of a secular-based ethics education course in New South Wales primary schools. Employing a Gramscian view of hegemony as an organising principle, the article aims to illustrate how ideological and political support for and against the ethics course is emblematic of hegemonic conflict centring upon the historical, ideological and political status of what is called Special Religious Education within New South Wales schools.
Pupils' Political Knowledge regarding the European Union
Authors: Oberle Monika
Published: October 2012

Young people's competencies to be enhanced by civic education in order to enable them to take part in society as active citizens have been intensely discussed by the scientific community. While the specific way of integrating political knowledge into theoretical models of competency is debated as a controversial issue, its relevance is generally accepted. In spite of its widely accepted salience, the empirical investigation of political knowledge is less developed than one might expect, partially due to measurement difficulties. The study presented here focuses on the political knowledge of German pupils in secondary and grammar schools, looking at both their objective and subjective (perceived, self-evaluated) knowledge with regard to the European Union (EU). The potential influence of various predicators on both types of knowledge – such as gender, cultural capital, migration background, school grade, news consumption, class climate and attitudes towards the EU – is determined and analysed. Furthermore, the design of the study allows for investigation of whether some factors systematically affect the relation between objective and subjective political knowledge – in other words, whether members of certain subgroups evaluate their individual EU knowledge differently. Among other implications, this would put the adequacy of self-reported knowledge as a proxy indicator for objective political knowledge into question.
Pursuing Better Childhoods and Futures through Curriculum: Utopian Visions in the Development of Australia's Early Years Learning Framework
Authors: Sumsion Jennifer , Grieshaber Susan
Published: October 2012

In recent years, globalised curriculum discourses have given rise to local curriculum texts that convey and produce particularised imaginings and narratives, as well as hopes for, and expectations of, young children, their childhoods and their futures. In this article, the authors employ concepts from utopian studies and Deleuzeguattarian concepts of assemblage, rhizomes and lines (supple, rigid and lines of flight) to undertake a preliminary and partial rhizomatic mapping of utopian visions of better childhoods and futures evident in the development of the Early Years Learning Framework, Australia's first national curriculum for early childhood settings. Drawing on the perspective of policy makers, News Corporation, the public, politicians, academics and practitioners who shaped the development of the Framework, the authors seek alternatives to the well-rehearsed dichotomies that so often characterise and confine curriculum politics and debates, and ways of exploring spaces between the possible and not (yet) possible.
Auditor-Provided Nonaudit Services and Audit Effectiveness and Efficiency: Evidence from Pre- and Post-SOX Audit Report Lags
Authors: Knechel W. Robert , Sharma Divesh S.
Published: October 2012

The Sarbanes-Oxley Act of 2002 (SOX) effectively bars an auditor from providing nonaudit services to an audit client based on the belief that the resulting economic bonding undermines the auditor's independence and quality of the audit (U.S. House of Representatives 2002). The accounting profession has strongly debated this view and counter-argues that auditor-provided nonaudit services benefit the client. We contribute to this debate by examining the effect of auditor-provided nonaudit services on the effectiveness and efficiency of the audit. We find that higher nonaudit service fees are associated with shorter audit report lags—a potential indicator of audit efficiency—prior to the passage of SOX, but such effects dissipate after SOX. We find that discretionary accruals and financial restatements—potential indicators of audit effectiveness—do not increase when shorter audit lags occur in conjunction with high nonaudit service fees. We also find that the firms with the highest levels of nonaudit service fees prior to SOX have the largest increase in audit lags after SOX. These results suggest that there is some merit to the profession's argument that auditor-provided nonaudit services benefit clients without leading to a loss of audit effectiveness.

Data Availability: All data are publicly available from sources identified in the text.
Audit Firm Governance: Do Transparency Reports Reveal Audit Quality?
Authors: Deumes Rogier , Schelleman Caren , Vander Bauwhede Heidi , Vanstraelen Ann
Published: October 2012

As a result of legal and regulatory requirements, audit firms in certain jurisdictions have recently started issuing transparency reports containing information on audit firm governance. In this study we investigate whether audit firm governance disclosure is associated with actual audit quality. Based on a sample of transparency reports of 103 audit firms in a number of EU countries, we find that there is variation in the extent and type of governance disclosures across audit firms. We, however, do not find an association with actual audit quality, apart from a weak association with an audit firm's statement on the effectiveness of its internal quality control system.

Data Availability: All data are available from public sources indicated in the study.
Investors' Response to Revelations of Prior Uncorrected Misstatements
Authors: Omer Thomas C. , Shelley Marjorie K. , Thompson Anne M.
Published: October 2012

This study examines investors' response to the disclosure of prior-period waived misstatements under Staff Accounting Bulletin (SAB) No. 108, Considering the Effects of Prior Year Misstatements When Quantifying Misstatements in the Current Year. Misstatement correction decisions typically are not observable, and financial statement users have little insight into the disposition of identified misstatements, a dimension of audit and financial statement quality. We find that investors respond negatively to the disclosure of SAB No. 108 misstatements, and this response is associated with the current-period auditor initially waiving the misstatement and client importance. Although SAB No. 108 misstatements were waived under prevailing materiality guidance, our findings suggest that investors interpret SAB No. 108 misstatements as indicating lower perceived audit quality.

Data Availability: Data are available from the sources indicated in the text.
Peninsula Effects on Birds in a Coastal Landscape: Are Coves More Species Rich than Lobes?
Authors: Riffell Sam , Keas Brian , Burton Thomas
Published: October 2012

Peninsula effects - decreasing richness with increasing distance along peninsula lobes - have been identified for many taxa on large peninsulas. Peninsula effects are caused by differences in colonization and extinction predicted by island biogeography or by environmental gradients along the peninsula. We compared species-area regressions for cove patches (i.e., mainland) to regressions for lobe patches (i.e., on peninsula tips) for wet meadow birds along a highly interdigitated shoreline (northern Lake Huron, USA). We conducted analysis both with and without accounting for variation in habitat and landscape characteristics (i.e., environmental gradients) of wet meadows. Species-area regressions for coves did not differ from lobes, nor did these results differ when we accounted for gradients. Similarly, few species were more abundant in coves. Peninsula effects may have been lacking because lobe patches were located ≈ 800 m on average from the mainland, and birds are highly mobile and can easily sample patches over these distances. One important caveat was that wet meadow patches > 5 ha were located in coves, so coves would still be important considerations in conservation plans because of the contribution of large patches to reproductive success, dispersal and population dynamics.
Exogenous hormone use, reproductive factors, and risk of intracranial meningioma in females
Authors: Claus Elizabeth B. , Calvocoressi Lisa , Bondy Melissa L. , Wrensch Margaret , Wiemels Joseph L. , Schildkraut Joellen M.
Published: October 2012

Object

The 2-fold higher incidence of meningioma in women compared with men has long suggested a role for hormonally mediated risk factors, but specific mechanisms remain elusive.

Methods

The study included data obtained in 1127 women 29–79 years of age with intracranial meningioma diagnosed among residents of Connecticut, Massachusetts, North Carolina, the San Francisco Bay Area, and 8 Texas counties between May 1, 2006, and October 6, 2011, and data obtained in 1092 control individuals who were frequency matched for age group and geography with meningioma patients.

Results

No association was observed for age at menarche, age at menopause, or parity and meningioma risk. Women who reported breastfeeding for at least 6 months were at reduced risk of meningioma (OR 0.78, 95% CI 0.63–0.96). A significant positive association existed between meningioma risk and increased body mass index (p < 0.01) while a significant negative association existed between meningioma risk and current smoking (p < 0.01). Among premenopausal women, current use of oral contraceptives was associated with an increased risk of meningiomas (OR 1.8, 95% CI 1.1–2.9), while current use of hormone replacement therapy among postmenopausal women was not associated with a significant elevation in risk (OR 1.1, 95% CI 0.74–1.67). There was no association between use of fertility medications and meningioma risk.

Conclusions

The authors' study confirms associations for body mass index, breastfeeding, and cigarette smoking but provides little evidence for associations of reproductive and menstrual factors with meningioma risk. The relationship between current use of exogenous hormones and meningioma remains unclear, limited by the small numbers of patients currently on oral hormone medications and a lack of hormone receptor data for meningioma tumors.
Symptomatic postsurgical cerebrospinal fluid leak treated by aspiration and epidural blood patch under ultrasound guidance in 2 adolescents
Authors: Fridley Jared S. , Jea Andrew , Glover Chris D. , Nguyen Kim P.
Published: October 2012

Cerebrospinal fluid leakage causing a pseudomeningocele is a well-recognized complication after spine surgery. The repair of pseudomeningocele in a symptomatic patient is usually accomplished with direct open surgical repair of the durotomy, prolonged lumbar drainage, and/or placement of an epidural blood patch. The authors highlight a unique method of pseudomeningocele repair by presenting 2 cases of adolescent girls with symptomatic lumbar pseudomeningoceles. In both cases ultrasound was used to guide the aspiration of CSF from each pseudomeningocele and to apply the epidural blood patch. Both patients had complete and immediate resolution of symptoms. The authors found ultrasound to be a useful tool to assess the extent of the CSF leakage, to determine the degree of aspiration of the extradural CSF, and to confirm the injection of the blood into the epidural space and the space created by the pseudomeningocele.