bluuebunny/crossref_metadata_2025 huggingface dataset:
Triple antiplatelet therapy for preventing vascular events: a systematic review and meta-analysis
Authors: Geeganage Chamila , Wilcox Robert , Bath Philip MW
Published: June 2010

Background

Dual antiplatelet therapy is usually superior to mono therapy in preventing recurrent vascular events (VEs). This systematic review assesses the safety and efficacy of triple antiplatelet therapy in comparison with dual therapy in reducing recurrent vascular events.

Methods

Completed randomized controlled trials investigating the effect of triple versus dual antiplatelet therapy in patients with ischaemic heart disease (IHD), cerebrovascular disease or peripheral vascular disease were identified using electronic bibliographic searches. Data were extracted on composite VEs, myocardial infarction (MI), stroke, death and bleeding and analysed with Cochrane Review Manager software. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using random effects models.

Results

Twenty-five completed randomized trials (17,383 patients with IHD) were included which involving the use of intravenous (iv) GP IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban), aspirin, clopidogrel and/or cilostazol. In comparison with aspirin-based therapy, triple therapy using an intravenous GP IIb/IIIa inhibitor significantly reduced composite VEs and MI in patients with non-ST elevation acute coronary syndromes (NSTE-ACS) (VE: OR 0.69, 95% CI 0.55-0.86; MI: OR 0.70, 95% CI 0.56-0.88) and ST elevation myocardial infarction (STEMI) (VE: OR 0.39, 95% CI 0.30-0.51; MI: OR 0.26, 95% CI 0.17-0.38). A significant reduction in death was also noted in STEMI patients treated with GP IIb/IIIa based triple therapy (OR 0.69, 95% CI 0.49-0.99). Increased minor bleeding was noted in STEMI and elective percutaneous coronary intervention (PCI) patients treated with GP IIb/IIIa based triple therapy. Stroke events were too infrequent for us to be able to identify meaningful trends and no data were available for patients recruited into trials on the basis of stroke or peripheral vascular disease.

Conclusions

Triple antiplatelet therapy based on iv GPIIb/IIIa inhibitors was more effective than aspirin-based dual therapy in reducing VEs in patients with acute coronary syndromes (STEMI and NSTEMI). Minor bleeding was increased among STEMI and elective PCI patients treated with a GP IIb/IIIa based triple therapy. In patients undergoing elective PCI, triple therapy had no beneficial effect and was associated with an 80% increase in transfusions and an eightfold increase in thrombocytopenia. Insufficient data exist for patients with prior ischaemic stroke and peripheral vascular disease and further research is needed in these groups of patients.
Long-term mortality prediction after operations for type A ascending aortic dissection
Authors: Macrina Francesco , Puddu Paolo E , Sciangula Alfonso , Totaro Marco , Trigilia Fausto , Cassese Mauro , Toscano Michele
Published: June 2010

Background

There are few long-term mortality prediction studies after acute aortic dissection (AAD) Type A and none were performed using new models such as neural networks (NN) or support vector machines (SVM) which may show a higher discriminatory potency than standard multivariable models.

Methods

We used 32 risk factors identified by Literature search and previously assessed in short-term outcome investigations. Models were trained (50%) and validated (50%) on 2 random samples from a consecutive 235-patient cohort. NN were run only on patients with complete data for all included variables (N = 211); SVM on the overall group. Discrimination was assessed by receiver operating characteristic area under the curve (AUC) and Gini's coefficients along with classification performance.

Results

There were 84 deaths (36%) occurring at 564 ± 48 days (95%CI from 470 to 658 days). Patients with complete variables had a slightly lower death rate (60 of 211, 28%). NN classified 44 of 60 (73%) dead patients and 147 of 151 (97%) long-term survivors using 5 covariates: immediate post-operative chronic renal failure, circulatory arrest time, the type of surgery on ascending aorta plus hemi-arch, extracorporeal circulation time and the presence of Marfan habitus. Global accuracies of training and validation NN were excellent with AUC respectively 0.871 and 0.870 but classification errors were high among patients who died. Training SVM, using a larger number of covariates, showed no false negative or false positive cases among 118 randomly selected patients (error = 0%, AUC 1.0) whereas validation SVM, among 117 patients, provided 5 false negative and 11 false positive cases (error = 22%, AUC 0.821, p < 0.01 versus NN results). An html file was produced to adopt and manipulate the selected parameters for practical predictive purposes.

Conclusions

Both NN and SVM accurately selected a few operative and immediate post-operative factors and the Marfan habitus as long-term mortality predictors in AAD Type A. Although these factors were not new per se, their combination may be used in practice to index death risk post-operatively with good accuracy.
Rituximab ameliorated severe hearing loss in Cogan's syndrome: a case report
Authors: Orsoni Jelka G , Laganà Bruno , Rubino Pierangela , Zavota Laura , Bacciu Salvatore , Mora Paolo
Published: June 2010

Background

Rituximab is a monoclonal antibody inducing depletion of B lymphocytes and presently approved for the treatment of non-Hodgkin's lymphoma and rheumatoid arthritis. Here is the first report of the use of this drug in a case of Cogan's syndrome (CS).

Case Presentation

a 25-year-old Italian woman was referred with conjunctival hyperaemia, interstitial keratitis, moderate bilateral sensorineural hearing loss accompanied by tinnitus, dizziness, nausea and vertigo, poorly responsive to oral and topical steroidal therapy. Diagnosis of typical CS was made. The administration of a combined immunosuppressive treatment resolved ocular inflammation, dizziness, nausea, and vertigo but gave little results in controlling progressive hearing loss. A noticeable improvement in hearing function was documented by pure tone audiometry after infusion of Rituximab.

Discussion

in CS, hearing function is often the most difficult parameter to control with therapy. A positive effect of Rituximab on was observed in our case. The drug also allowed to significantly reduce the number of adjuvant immunosuppressive medications.
Protein interaction network topology uncovers melanogenesis regulatory network components within functional genomics datasets
Authors: Ho Hsiang , Milenković Tijana , Memišević Vesna , Aruri Jayavani , Pržulj Nataša , Ganesan Anand K
Published: June 2010

Background

RNA-mediated interference (RNAi)-based functional genomics is a systems-level approach to identify novel genes that control biological phenotypes. Existing computational approaches can identify individual genes from RNAi datasets that regulate a given biological process. However, currently available methods cannot identify which RNAi screen "hits" are novel components of well-characterized biological pathways known to regulate the interrogated phenotype. In this study, we describe a method to identify genes from RNAi datasets that are novel components of known biological pathways. We experimentally validate our approach in the context of a recently completed RNAi screen to identify novel regulators of melanogenesis.

Results

In this study, we utilize a PPI network topology-based approach to identify targets within our RNAi dataset that may be components of known melanogenesis regulatory pathways. Our computational approach identifies a set of screen targets that cluster topologically in a human PPI network with the known pigment regulator Endothelin receptor type B (EDNRB). Validation studies reveal that these genes impact pigment production and EDNRB signaling in pigmented melanoma cells (MNT-1) and normal melanocytes.

Conclusions

We present an approach that identifies novel components of well-characterized biological pathways from functional genomics datasets that could not have been identified by existing statistical and computational approaches.
Expression of the zic1, zic2, zic3, and zic4 genes in early chick embryos
Authors: McMahon Ariel R , Merzdorf Christa S
Published: June 2010

Background

The zic genes encode a family of transcription factors with important roles during early development. Since little is known about zic gene expression in chick embryos, we have characterized the expression patterns of the zic1, zic2, zic3, and zic4 (zic1-4) genes during neurulation and somitogenesis.

Findings

We used in situ hybridization to analyze the expression patterns of the zic1-4 genes during early chick development (HH stages 7-19). The zic1-3 genes showed both overlapping and gene-specific expression patterns along the length of the dorsal neural tube and in the dorsal parts of the somites. In addition, unique expression domains of zic genes included: zic2 in the neural plate, periotic mesoderm and limb buds; zic3 in the paraxial mesoderm surrounding the neural plate, in presomitic mesoderm and in the most recently formed epithelial somites; zic2 and zic3 in developing eyes. zic4 expression was limited to dorsal fore- and midbrain regions and, unlike the expression of the zic1-3 genes, zic4 expression was not detected in the hindbrain and trunk. This was in contrast to more extensive zic4 expression in other vertebrates.

Conclusions

The zic1-3 genes were expressed in both overlapping and unique domains within the neural tube, somites and other ectoderm and mesoderm-derived structures in the future head and trunk. zic4 expression, however, was limited to dorso-anterior regions of the future brain. This is the first comprehensive study of zic1-4 gene expression in chick embryos during neurulation and somitogenesis.
Relationships between foot type and dynamic rearfoot frontal plane motion
Authors: Chuter Vivienne H
Published: June 2010

Background

The Foot Posture Index (FPI) provides an easily applicable, validated method for quantifying static foot posture. However there is limited evidence relating to the ability of the FPI to predict dynamic foot function. This study aimed to assess the relationship between dynamic rearfoot motion and FPI scores in pronated and normal foot types.

Methods

40 participants were recruited with equal numbers of pronated and normal foot types as classified by their FPI score. Three dimensional rearfoot motion was collected for each of the participants. Dynamic maximum rearfoot eversion was correlated with the total FPI score across all participants and within the normal and pronated foot types. Linear correlations were performed between components of the total FPI scores measuring frontal plane rearfoot position and maximum rearfoot eversion. The capacity of the total FPI score to predict maximum frontal plane motion of the rearfoot was investigated using linear regression analysis.

Results

The correlation between the total FPI score and maximum rearfoot eversion was strongly positive (r = 0.92, p < 0.05). Correlation performed on data subsets demonstrated the pronated foot type (FPI = +6 to +9) and maximum rearfoot eversion angle were more strongly positively correlated (r = 0.81, p < 0.05) than the normal foot type (FPI = 0 to +5) and maximum rearfoot eversion (r = 0.76, p < 0.05). Correlations between frontal plane rearfoot FPI score and frontal plane motion during gait were strongly positive, (r = 0.79 p < 0.05 pronated group, r = 0.71 p < 0.05 normal group), however were less strong than the total FPI score and rearfoot motion. Linear regression analysis demonstrated a significant and strong relationship between the total FPI score and maximum rearfoot eversion (r2 = 0.85, p < 0.001).

Conclusions

The results of this study suggest the FPI has strong predictive ability for dynamic rearfoot function. This will assist in clinical screening and research by allowing easy classification by functional foot type. Positive correlations between frontal plane rearfoot measurements and maximum rearfoot eversion suggest the FPI may identify dominant planar components of dynamic rearfoot motion and warrants further investigation.
Alternative management of diabetic ketoacidosis in a Brazilian pediatric emergency department
Authors: Savoldelli Roberta D , Farhat Sylvia CL , Manna Thais D
Published: June 2010

DKA is a severe metabolic derangement characterized by dehydration, loss of electrolytes, hyperglycemia, hyperketonemia, acidosis and progressive loss of consciousness that results from severe insulin deficiency combined with the effects of increased levels of counterregulatory hormones (catecholamines, glucagon, cortisol, growth hormone). The biochemical criteria for diagnosis are: blood glucose > 200 mg/dl, venous pH <7.3 or bicarbonate <15 mEq/L, ketonemia >3 mmol/L and presence of ketonuria. A patient with DKA must be managed in an emergency ward by an experienced staff or in an intensive care unit (ICU), in order to provide an intensive monitoring of the vital and neurological signs, and of the patient's clinical and biochemical response to treatment. DKA treatment guidelines include: restoration of circulating volume and electrolyte replacement; correction of insulin deficiency aiming at the resolution of metabolic acidosis and ketosis; reduction of risk of cerebral edema; avoidance of other complications of therapy (hypoglycemia, hypokalemia, hyperkalemia, hyperchloremic acidosis); identification and treatment of precipitating events. In Brazil, there are few pediatric ICU beds in public hospitals, so an alternative protocol was designed to abbreviate the time on intravenous infusion lines in order to facilitate DKA management in general emergency wards. The main differences between this protocol and the international guidelines are: intravenous fluid will be stopped when oral fluids are well tolerated and total deficit will be replaced orally; if potassium analysis still indicate need for replacement, it will be given orally; subcutaneous rapid-acting insulin analog is administered at 0.15 U/kg dose every 2-3 hours until resolution of metabolic acidosis; approximately 12 hours after treatment initiation, intermediate-acting (NPH) insulin is initiated at the dose of 0.6-1 U/kg/day, and it will be lowered to 0.4-0.7 U/kg/day at discharge from hospital.
A model for the molecular organisation of the IS911 transpososome
Authors: Rousseau Philippe , Tardin Catherine , Tolou Nathalie , Salomé Laurence , Chandler Mick
Published: June 2010

Tight regulation of transposition activity is essential to limit damage transposons may cause by generating potentially lethal DNA rearrangements. Assembly of a bona fide protein-DNA complex, the transpososome, within which transposition is catalysed, is a crucial checkpoint in this regulation. In the case of IS911, a member of the large IS3 bacterial insertion sequence family, the transpososome (synaptic complex A; SCA) is composed of the right and left inverted repeated DNA sequences (IRR and IRL) bridged by the transposase, OrfAB (the IS911-encoded enzyme that catalyses transposition). To characterise further this important protein-DNA complex in vitro, we used different tagged and/or truncated transposase forms and analysed their interaction with IS911 ends using gel electrophoresis. Our results allow us to propose a model in which SCA is assembled with a dimeric form of the transposase. Furthermore, we present atomic force microscopy results showing that the terminal inverted repeat sequences are probably assembled in a parallel configuration within the SCA. These results represent the first step in the structural description of the IS911 transpososome, and are discussed in comparison with the very few other transpososome examples described in the literature.
Only one independent genetic association with rheumatoid arthritis within the KIAA1109-TENR-IL2-IL21 locus in Caucasian sample sets: confirmation of association of rs6822844with rheumatoid arthritis at a genome-wide level of significance
Authors: Hollis-Moffatt Jade E , Chen-Xu Michael , Topless Ruth , Dalbeth Nicola , Gow Peter J , Harrison Andrew A , Highton John , Jones Peter BB , Nissen Michael , Smith Malcolm D , van Rij Andre , Jones Gregory T , Stamp Lisa K , Merriman Tony R
Published: June 2010

Introduction

The single nucleotide polymorphism (SNP) rs6822844 within the KIAA1109-TENR-IL2-IL21 gene cluster has been associated with rheumatoid arthritis (RA). Other variants within this cluster, including rs17388568 that is not in linkage disequilibrium (LD) with rs6822844, and rs907715 that is in moderate LD with rs6822844 and rs17388568, have been associated with a number of autoimmune phenotypes, including type 1 diabetes (T1D). Here we aimed to: one, confirm at a genome-wide level of significance association of rs6822844 with RA and, two, evaluate whether or not there were effects independent of rs6822844 on RA at the KIAA1109-TENR-IL2-IL21 locus.

Methods

A total of 842 Australasian RA patients and 1,115 controls of European Caucasian ancestry were genotyped for rs6822844, rs17388568 and rs907715. Meta-analysis of these data with published and publicly-available data was conducted using STATA.

Results

No statistically significant evidence for association was observed in the Australasian sample set for rs6822844 (odds ratio (OR) = 0.95 (0.80 to 1.12), P = 0.54), or rs17388568 (OR = 1.03 (0.90 to 1.19), P = 0.65) or rs907715 (OR = 0.98 (0.86 to 1.12), P = 0.69). When combined in a meta-analysis using data from a total of 9,772 cases and 10,909 controls there was a genome-wide level of significance supporting association of rs6822844 with RA (OR = 0.86 (0.82 to 0.91), P = 8.8 × 10-8, P = 2.1 × 10-8 including North American Rheumatoid Arthritis Consortium data). Meta-analysis of rs17388568, using a total of 6,585 cases and 7,528 controls, revealed no significant association with RA (OR = 1.03, (0.98 to 1.09); P = 0.22) and meta-analysis of rs907715 using a total of 2,689 cases and 4,045 controls revealed a trend towards association (OR = 0.93 (0.87 to 1.00), P = 0.07). However, this trend was not independent of the association at rs6822844.

Conclusions

The KIAA1109-TENR-IL2-IL21 gene cluster, that encodes an interleukin (IL-21) that plays an important role in Th17 cell biology, is the 20th locus for which there is a genome-wide (P ≤ 5 ×10-8) level of support for association with RA. As for most other autoimmune diseases, with the notable exception of T1D, rs6822844 is the dominant association in the locus. The KIAA1109-TENR-IL2-IL21 locus also confers susceptibility to other autoimmune phenotypes with a heterogeneous pattern of association.
Notochordal cell conditioned medium stimulates mesenchymal stem cell differentiation toward a young nucleus pulposus phenotype
Authors: Korecki Casey L , Taboas Juan M , Tuan Rocky S , Iatridis James C
Published: June 2010

Introduction

Mesenchymal stem cells (MSCs) offer promise for intervertebral disc (IVD) repair and regeneration because they are easily isolated and expanded, and can differentiate into several mesenchymal tissues. Notochordal (NC) cells contribute to IVD development, incorporate into the nucleus pulposus (NP), and stimulate mature disc cells. However, there have been no studies investigating the effects of NC cells on adult stem cell differentiation. The premise of this study is that IVD regeneration is more similar to IVD development than to IVD maintenance, and we hypothesize that soluble factors from NC cells differentiate MSCs to a phenotype characteristic of nucleus pulposus (NP) cells during development. The eventual clinical goal would be to isolate or chemically/recombinantly produce the active agent to induce the therapeutic effects, and to use it as either an injectable therapy for early intervention on disc disease, or in developing appropriately pre-differentiated MSC cells in a tissue engineered NP construct.

Methods

Human MSCs from bone marrow were expanded and pelleted to form high-density cultures. MSC pellets were exposed to either control medium (CM), chondrogenic medium (CM with dexamethasone and transforming growth factor, (TGF)-β3) or notochordal cell conditioned medium (NCCM). NCCM was prepared from NC cells maintained in serum free medium for four days. After seven days culture, MSC pellets were analyzed for appearance, biochemical composition (glycosaminoglycans and DNA), and gene expression profile (sox-9, collagen types-II and III, laminin-β1 and TIMP1(tissue inhibitor of metalloproteinases-1)).

Results

Significantly higher glycosaminoglycan accumulation was seen in NCCM treated pellets than in CM or TGFβ groups. With NCCM treatment, increased gene expression of collagen III, and a trend of increasing expression of laminin-β1 and decreased expression of sox-9 and collagen II relative to the TGFβ group was observed.

Conclusions

Together, results suggest NCCM stimulates mesenchymal stem cell differentiation toward a potentially NP-like phenotype with some characteristics of the developing IVD.
A curve-fitting technique for determining dispersion characteristics of guided elastic waves
Authors: Tang Xiao-Ming , Li Chen , Patterson Douglas J.
Published: June 2010

We have developed a novel curve-fitting method to estimate dispersion characteristics of guided elastic waves and investigate its application to field wireline and logging while drilling (LWD) acoustic data processing. In an elastic waveguide such as a fluid-filled borehole with a logging tool, the frequency dispersion of a guided-wave mode is characterized by a monotonically varying dispersion curve bounded by its low- and high-frequency limits. The detailed behavior of the curves relates to various elastic/acoustic parameters of the complicated waveguide structure. The novelty of the proposed technique is that it simulates the multiparameter dispersion curve using a simple analytical function that has only four parameters. By adjusting the four parameters to fit the actual wave dispersion data, the wave’s dispersion characteristics can be satisfactorily determined. The result of this simple approach leads to several important applications in acoustic logging. The first is to correct the dispersion effect in the shear-wave velocity from wireline dipole acoustic logging. The second application obtains P-wave velocity from the dispersive leaky compressional-wave data from wireline or LWD measurements. Third, the technique is applied to obtain shear-wave velocity from LWD quadrupole shear-wave logging. Finally, the technique is applicable to layered waveguide structures encountered in surface seismic exploration.
Simulation of triaxial induction measurements in dipping, invaded, and anisotropic formations using a Fourier series expansion in a nonorthogonal system of coordinates and a self-adaptive hp finite-element method
Authors: Nam Myung Jin , Pardo David , Torres-Verdín Carlos
Published: June 2010

Borehole triaxial induction instruments were designed to diagnose and measure rock electrical conductivity parallel and perpendicular to the bedding plane. Experience has shown that the interpretation of triaxial induction measurements often requires numerical modeling for a proper diagnosis of rock electrical conductivity anisotropy in the presence of geometric effects such as dipping wells, layer boundaries, and invasion. We introduce a new algorithm to simulate triaxial induction measurements that combines a Fourier series expansion in a nonorthogonal system of coordinates with a 2D goal-oriented, self-adaptive, high-order [Formula: see text] finite-element method. This procedure enables the accurate and reliable simulation of triaxial induction measurements across reservoir rock formations with extreme contrasts of electrical conductivity while reducing the 3D computational complexity associated with deviated wells. Numerical results indicate that borehole dip effects on triaxial induction measurements are larger than on standard coaxial induction measurements. The sensitivity of triaxial induction measurements to transversely isotropic rock formations decreases with increasing dip angle.
The nuclear protein Waharan is required for endosomal-lysosomal trafficking inDrosophila
Authors: Lone Mohiddin , Kungl Theresa , Koper Andre , Bottenberg Wolfgang , Kammerer Richard , Klein Melanie , Sweeney Sean T. , Auburn Richard P. , O'Kane Cahir J. , Prokop Andreas
Published: June 2010

Here we report Drosophila Waharan (Wah), a 170-kD predominantly nuclear protein with two potential human homologues, as a newly identified regulator of endosomal trafficking. Wah is required for neuromuscular-junction development and muscle integrity. In muscles, knockdown of Wah caused novel accumulations of tightly packed electron-dense tubules, which we termed ‘sausage bodies’. Our data suggest that sausage bodies coincide with sites at which ubiquitylated proteins and a number of endosomal and lysosomal markers co-accumulate. Furthermore, loss of Wah function generated loss of the acidic LysoTracker compartment. Together with data demonstrating that Wah acts earlier in the trafficking pathway than the Escrt-III component Drosophila Shrb (snf7 in Schizosaccharomyces pombe), our results indicate that Wah is essential for endocytic trafficking at the late endosome. Highly unexpected phenotypes result from Wah knockdown, in that the distribution of ubiquitylated cargos and endolysosomal morphologies are affected despite Wah being a predominant nuclear protein. This finding suggests the existence of a relationship between nuclear functions and endolysosomal trafficking. Future studies of Wah function will give us insights into this interesting phenomenon.
Enhancing search efficiency by means of a search filter for finding all studies on animal experimentation in PubMed
Authors: Hooijmans Carlijn R , Tillema Alice , Leenaars Marlies , Ritskes-Hoitinga Merel
Published: June 2010

Collecting and analysing all available literature before starting an animal experiment is important and it is indispensable when writing a systematic review (SR) of animal research. Writing such review prevents unnecessary duplication of animal studies and thus unnecessary animal use (Reduction). One of the factors currently impeding the production of ‘high-quality’ SRs in laboratory animal science is the fact that searching for all available literature concerning animal experimentation is rather difficult. In order to diminish these difficulties, we developed a search filter for PubMed to detect all publications concerning animal studies. This filter was compared with the method most frequently used, the PubMed Limit: Animals, and validated further by performing two PubMed topic searches. Our filter performs much better than the PubMed limit: it retrieves, on average, 7% more records. Other important advantages of our filter are that it also finds the most recent records and that it is easy to use. All in all, by using our search filter in PubMed, all available literature concerning animal studies on a specific topic can easily be found and assessed, which will help in increasing the scientific quality and thereby the ethical validity of animal experiments.
The Maximum Possible EVPI
Authors: Drezner Zvi
Published: June 2010

In this note we calculate the maximum EVPI for any probability distribution for the states of the world. This maximum EVPI is an upper bound for the EVPI with given probabilities and thus an upper bound for any partial information about the states of the world.
Case Article—MotherLand Air: Using Experiential Learning to Teach Revenue Management Concepts
Authors: Metters Richard , Vargas Vicente , Weaver Sherry
Published: June 2010

The MotherLand Air case and game provide students with a first-hand experience in revenue management. The game is conducted in the classroom, and students, who have the opportunity to prepare in advance, work in teams. During the exercise, students make and revise pricing and protection-level decisions over a six-month, predeparture time horizon for two simulated flights. The case provides an introduction to nested reservation systems and overbooking and pricing polices.

Case Teaching Note: Interested Instructors please see the Instructor Materials page for access to the restricted materials. To maintain the integrity and usefulness of cases published in ITE, unapproved distribution of the case teaching notes and other restricted materials to any other party is prohibited.
Case Article—Starting with Good Inputs: Unconstraining Demand Data in Revenue Management
Authors: Ferguson Mark , Queenan Carrie
Published: June 2010

Sales of goods and services are often limited by supply. This limitation restricts the knowledge of the true parameter values for the underlying demand distributions, values needed to calculate optimal protection levels in a revenue management system. We provide a teaching module and a case study to introduce students to the dangers of using “constrained demand.” The teaching module illustrates the negative financial impact of failing to unconstrain demand data. The case study provides realistic constrained demand data that students can use to practice unconstraining methods, such as the commonly used averaging method. We have used these materials successfully in MBA and executive education classes on revenue management.

Case Teaching Note: Interested Instructors please see the Instructor Materials page for access to the restricted materials. To maintain the integrity and usefulness of cases published in ITE, unapproved distribution of the case teaching notes and other restricted materials to any other party is prohibited.
Case Article—Introductory Integrative Cases on Airline Revenue Management
Authors: Shumsky Robert A.
Published: June 2010

This case article summarizes two case series. Each case series includes three subcases and has an associated teaching note. These six short cases introduce many of the concepts that underlie the practice of airline revenue management: protection levels, overbooking, customer buy-up and buy-down behavior, network controls, bid prices, and the spiral-down effect. The cases are integrative in the sense that they reinforce many of the fundamental concepts taught in business programs, such as the formulation of statistical models, customer segmentation, the meaning of shadow prices in optimization, and the impact of model errors on real-world decisions. The cases also use many of the basic skills and tools taught in business programs: data analysis and forecasting, simulation, and optimization. By applying these tools, the cases move students quickly beyond the standard newsvendor-style formulation of the revenue management problem. Because the cases require students to apply these tools to interesting and relatively complex revenue management problems, the tools themselves gain more credibility among the students.

Case Teaching Note: Interested Instructors please see the Instructor Materials page for access to the restricted materials. To maintain the integrity and usefulness of cases published in ITE, unapproved distribution of the case teaching notes and other restricted materials to any other party is prohibited.
Web-based Simulations for Teaching Queueing, Little's Law, and Inventory Management
Authors: Dobson Gregory , Shumsky Robert
Published: June 2010

We describe and make available three web-based simulations that help to teach concepts related to process flow and variability. These programs simulate, (i) a G/G/1 queue, (ii) a single-stage process to demonstrate the long-run validity of Little's Law and (iii) a continuous-time reorder point/reorder quantity inventory system. All of the simulations are interactive, for they allow users to change system parameters by moving simple sliders. The simulations do not require specialized software to run and are available through any web browser. We offer evidence of how the simulations have helped the students to learn, including documentation from a web-based exercise with the queueing simulation that was completed by 74 students.

This document describes three web-based simulations that help students understand the dynamics of continuoustime systems subject to variability. The simulations have been useful in introductory MBA operations management courses, and they would also be appropriate for undergraduate courses in operations research and operations management. Given that the simulations are simple to use and entertaining to watch, they may also be appropriate for high school students to motivate the study of operations research.

This document describes the simulations, the pedagogical goals that motivated their development, alternate teaching tools that are available to instructors, and how we have used the simulations in the classroom. We end with a description of how the models helped our students to learn the concepts, including a summary of the students' answers to a set of web-based exercises with one of the simulations.
An Interactive Excel VBA Example for Teaching Statistics Concepts
Authors: Tsai Weiyu , Wardell Don G.
Published: June 2010

It is often challenging for business students to learn abstract statistical concepts and apply these concepts to their work. Three concepts in particular that we have found difficult to communicate effectively are the Central Limit Theorem, interval estimation and hypothesis testing. To improve the effectiveness of teaching these fundamental statistical concepts, we developed a Visual Basic for Applications (VBA) driven Excel spreadsheet that is built around one simple business scenario. The scenario involves setting the filling speed in a cereal filling plant. The faster the filling speed, the larger the variation in cereal box weights and the higher the chance of having an out-of-control filling process. On the other hand, the lower the filling speed, the less efficient the plant is at utilizing capacity. Through interactively finding the optimal filling speed, students are exposed to these key statistics concepts as well as random sampling techniques. Hence, we integrate the illustration of three important statistical concepts in one simple yet practical business scenario. Moreover, the Excel VBAdriven example demonstrates several Excel statistical formulae that are useful to business students. We conducted an in-class open-book quiz to two sections of professional MBA students to assess teaching effectiveness of this interactive example. The results showed that the scores of those using the interactive VBA demo were superior to those exposed to more traditional techniques at 10% significance level. A follow-up on-line feedback survey further supported the usage of the Excel VBA-driven example in enhancing student learning.
Integrating Spreadsheet Engineering in a Management Science Course: A Hierarchical Approach
Authors: Grossman Thomas A.
Published: June 2010

Business students who rely on spreadsheets can use management science only to the extent that they can build a spreadsheet model of an unstructured business situation. Spreadsheets are the primary vehicle for analytical work in business, are advantageous for modeling and model representation, and are used by management science practitioners as well as end-user modelers. There is a common misperception that spreadsheets are somehow “easy” to use. However, the spreadsheet is a powerful rapid development computer programming language that requires software engineering for serious work. People struggle to efficiently build effective, transferable spreadsheet models. Students need certain spreadsheet engineering principles that they do not know, but value highly when they learn them. Spreadsheet engineering can be taught using a hierarchical “Skills, Capabilities and Practices Model.” Low-level “Skills” need to be evaluated and fixed early in a spreadsheetoriented management science course. High-level “Capabilities” and “Practices” should be integrated throughout the course. Embracing spreadsheet engineering provides a magnificent opportunity for management science instructors to increase relevance and student satisfaction while increasing the likelihood of management science application by our graduates.
Integrating MS/OR Modeling into an ERP Course
Authors: Flowers A. Dale
Published: June 2010

ERP is a subject with widespread applicability in industry, and one that presents challenges for companies to successfully implement. In this paper, I describe a graduate course in Enterprise Resource Planning (ERP) systems that integrates a whole series of MS/OR based case studies into the course, where all the cases are from the same company. The cases range from detailed and operational issues such as the bill of material explosion to more strategic issues such as hierarchical production planning and distribution network design. The data rich environment that ERP systems create is very fertile ground for the development and implementation of decision support systems via MS/OR modeling. This is an opportunity our profession should not overlook. This integrated set of case studies is facilitated via the use of one multi-function modeling package that makes it easy for students to use for the semester long course. The course is highly rated in the teaching evaluations that students complete, and the anecdotal feedback is that it is good preparation for the business world.
Using AMPL for Teaching the TSP
Authors: Lee Jon , Raffensperger John F.
Published: June 2010

In this paper, we discuss the use of AMPL in teaching students about the traveling salesman problem (TSP). The paper gives suggestions for pedagogical devices, homework assignments and exams, PowerPoint presentations, and a convenient package of AMPL models and scripts. The AMPL files include different formulations for the TSP, its relaxations, scripts for its solution, and - particularly useful in class - scripts for visualization of those solutions using SVG. We have a special focus on visualization, to provide convenient ways for students to view and report their solutions. We observe that the TSP is such a classical O.R. problem, that it can play a central role in an undergraduate course about integer programming.
Introducing Integer Modeling with Excel Solver
Authors: Pachamanova Dessislava
Published: June 2010

This article suggests ideas for introducing integer modeling of fixed (entry) costs with Excel Solver to business students. The presented example uses concepts from accounting, such as assessing distribution channel profitability, and blends them with management science techniques. The effectiveness of the software use is in integrating it successfully into a comprehensive discussion about assumptions, modeling, limitations, software pitfalls, validation, and implications for managerial decision making.
An Electronic Teaching Assistant for Basic Operations Management Methods
Authors: Scheubrein Ralph J. , Kulturel-Konak Sadan
Published: June 2010

Software packages are frequently used to support the teaching of quantitative methods. In one possible approach, the educator demonstrates how to use a software package which implements the method considered in the lecture. In an alternative approach, students have to implement the considered method on their own. A popular type of software package used in Master of Business Administration classes for the second approach is the spreadsheet, since students can “program” in an intuitive way by entering formulas in the cells of the worksheet. While letting students implement a method on their own normally takes much longer than just a demonstration by the educator, it can be argued that the students develop a better understanding of the method through active learning. In this context, the spreadsheet-based tutoring system ExcelTutor was developed to help students learn the steps necessary to compute the results of a specific method. After a student has formulated the method on his or her own, ExcelTutor verifies the correctness of the final results and provides feedback on the time needed for the implementation.
Intravenous Artesunate for the Treatment of Severe Malaria
Authors: Hess Karl M , Goad Jeffery A , Arguin Paul M
Published: June 2010

Objective:

To review the pharmacodynamics and pharmacotherapeutic use of intravenous artesunate for the treatment of severe malaria.

Data Sources:

Literature was retrieved through PubMed (1999–March 2010), MEDLINE (1996–March 2010), and the Centers for Disease Control and Prevention (CDC), using the search terms artemisinin, artesunate, malaria, and severe malaria. In addition, reference citations from publications identified were reviewed.

Study Selection and Data Extraction:

All articles in English that were identified from the data sources were reviewed. Focus was placed on postmarketing trials examining the safety and efficacy of artesunate in comparison with other regimens.

Data Synthesis:

The treatment of severe malaria requires prompt, safe, and effective intravenous antimalarials. Many oral and intravenous agents are available worldwide for the treatment of malaria; however, quinidine has been the only option for parenteral therapy in the US. Furthermore, this product's lack of availability as well as its adverse safety profile have created a treatment option gap. Recently, intravenous artesunate was approved by the Food and Drug Administration (FDA) for investigational drug use and distribution by the CDC. Three major studies regarding the use of intravenous artesunate are reviewed, in addition to the World Health Organization's malaria treatment guidelines. While there are no published head-to-head trials of intravenous artesunate versus intravenous quinidine for severe malaria, several international studies comparing intravenous quinine and artesunate concluded that artesunate has the highest treatment success, with lower incidence of adverse events. In addition, other literature is reviewed regarding counterfeit and other issues associated with artesunate.

Conclusions:

Artesunate, a new antimalarial currently available through the CDC, appears to be highly effective, better tolerated than quinidine, and not hampered by accessibility issues. If it were to be FDA approved and commercially available, it would be the preferred agent for the treatment of severe malaria in the US.
Methylation-Specific Loop-Mediated Isothermal Amplification for Detecting Hypermethylated DNA in Simplex and Multiplex Formats
Authors: Zerilli Francesco , Bonanno Cinzia , Shehi Erlet , Amicarelli Giulia , Adlerstein Daniel , Makrigiorgos G Mike
Published: June 2010

BACKGROUND

Aberrant DNA methylation of gene promoters and the associated silencing of tumor suppressor genes are recognized as mechanisms contributing to tumor development. Therefore, detection of promoter hypermethylation is becoming important for diagnosis, prognosis, and aiding the design of cancer therapies. We describe a novel isothermal method for the detection of DNA hypermethylation.

METHODS

Methylation-specific loop-mediated isothermal amplification (MS-LAMP) is a novel adaptation of LAMP. MS-LAMP was used for the highly specific detection of hypermethylated CpGs in the promoters of the CDKN2A [cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)], GATA5 (GATA binding protein 5), and DAPK1 (death-associated protein kinase 1) genes. The reactions occurred under isothermal conditions with 3 primer sets specific for methylated promoters. Both turbidimetry and fluorescence were used for detection. The MS-LAMP assay was validated with bisulfite-treated plasmid and genomic DNA controls of known methylation status and was applied to detect hypermethylation in 18 clinical tumor samples. A multiplex MS-LAMP for CDKN2A, GATA5, and DAPK1 was also validated with the aid of synthetic positive and negative controls.

RESULTS

The MS-LAMP assay showed high specificity with plasmid and genomic DNA targets in reactions carried out in <1 h. The assay had a detection limit of approximately 30 copies of methylated target sequence and a selectivity of 0.5% methylated DNA in a mixture with unmethylated DNA. Compared with methylation-specific PCR, the MS-LAMP assay detected lower rates of methylation in lung adenocarcinoma samples. Simultaneous multiplex detection of hypermethylation in the 3 targets (CDKN2A, GATA5, and DAPK1) was readily achieved with the MS-LAMP assay in both the turbidimetric and fluorescence detection formats.

CONCLUSIONS

MS-LAMP provides a highly specific isothermal method for methylation detection and is well suited for multiplex approaches.
Estimation of the Minimal Preanalytical Uncertainty for 15 Clinical Chemistry Serum Analytes
Authors: Sylte Marit Sverresdotter , Wentzel-Larsen Tore , Bolann Bjørn J
Published: June 2010

BACKGROUND

We sought a model to estimate preanalytical uncertainty of blood samples collected and processed by using optimal procedures.

METHODS

Optimal preanalytical handling of blood samples included use of a loosely fastened tourniquet, wide bore needles, recommended clotting time and centrifugation speed, and minimal storage before analysis. Blood was collected from each arm of 20 volunteers into 2 rapid-serum tubes and 2 serum-separation tubes. Linear mixed-effects models were used to estimate the between-venipuncture SD, the preanalytical SD (excluding venipuncture), the measurement repeatability SD, and systematic differences between the tubes and between venipunctures.

RESULTS

No significant systematic differences were found between successive venipunctures. However, statistically significant mean differences were seen between serum-separation tubes and rapid-serum tubes for 7 of the 15 analytes. The preanalytical SD (excluding venipuncture) for lactate dehydrogenase (3.2 U/L, 95% CI 2.8–3.7) was significantly higher than the SD for measurement repeatability (1.9 U/L, 95% CI 1.7–2.1). For potassium both the preanalytical SD (excluding venipuncture) (0.092 mmol/L, 95% CI 0.080–0.11) and the between-venipuncture SD (0.075 mmol/L, 95% CI 0.048–0.12) were significantly higher than the measurement-repeatability SD (0.031 mmol/L, 95% CI 0.028–0.035). For glucose the between-venipuncture SD (0.20 mmol/L, 95% CI 0.14–0.27) was significantly higher than the preanalytical SD (excluding venipuncture) (0.07 mmol/L, 95% CI 0.06–0.08), and the measurement repeatability SD (0.057 mmol/L, 95% CI 0.051–0.064).

CONCLUSIONS

By applying linear mixed-effects models we have estimated the minimal preanalytical uncertainty that will influence all patient results.
Lipoprotein(a) and Risk of Type 2 Diabetes
Authors: Mora Samia , Kamstrup Pia R , Rifai Nader , Nordestgaard Børge G , Buring Julie E , Ridker Paul M
Published: June 2010

BACKGROUND

Previous studies have demonstrated that cardiovascular risk is higher with increased lipoprotein(a) [Lp(a)]. Whether Lp(a) concentration is related to type 2 diabetes is unclear.

METHODS

In 26 746 healthy US women (mean age 54.6 years), we prospectively examined baseline Lp(a) concentrations and incident type 2 diabetes (n = 1670) for a follow-up period of 13 years. We confirmed our findings in 9652 Danish men and women with prevalent diabetes (n = 419). Analyses were adjusted for risk factors that included age, race, smoking, hormone use, family history, blood pressure, body mass index, hemoglobin A1c (Hb A1c), C-reactive protein, and lipids.

RESULTS

Lp(a) was inversely associated with incident diabetes, with fully adjusted hazard ratios (HRs) and 95% CIs for quintiles 2–5 vs quintile 1 of 0.87 (0.75–1.01), 0.80 (0.68–0.93), 0.88 (0.76–1.02), and 0.78 (0.67–0.91); P for trend 0.002. The association was stronger in nonfasting women, for whom respective HRs were 0.79 (0.58–1.09), 0.78 (0.57–1.08), 0.66 (0.46–0.93), and 0.56 (0.40–0.80); P for trend 0.001; P for interaction with fasting status 0.002. When we used Lp(a) ≥10 mg/L and Hb A1c <5% as reference values, the adjusted HRs were 1.62 (0.91–2.89) for Lp(a) <10 mg/L and Hb A1c <5%, 3.50 (3.06–4.01) for Lp(a)≥10 mg/L and Hb A1c 5%–<6.5%, and 5.36 (4.00–7.19) for Lp(a) <10 mg/L and Hb A1c 5%–<6.5%. Results were similar in nonfasting Danish men and women, for whom adjusted odds ratios were 0.75 (0.55–1.03), 0.64 (0.46–0.88), 0.74 (0.54–1.01), and 0.58 (0.42–0.79) for Lp(a) quintiles 2–5 vs quintile 1; P for trend 0.002.

CONCLUSIONS

Our results indicated that Lp(a) was associated inversely with risk of type 2 diabetes independently of risk factors, in contrast to prior findings of positive associations of Lp(a) with cardiovascular risk.