bluuebunny/crossref_metadata_2025 huggingface dataset:
A constant risk for familial breast cancer? A population-based family study
Authors: Czene Kamila , Reilly Marie , Hall Per , Hartman Mikael
Published: May 2009

Introduction

The incidence of breast cancer in the unaffected breast of women with previous breast malignancy remains constant after the first diagnosis. We investigated whether there is a similar pattern in the breast cancer incidence in first-degree relatives of breast cancer patients. We studied the risk for breast cancer in mothers at ages older than their daughter's age at diagnosis.

Methods

We analyzed a Swedish population-based cohort with complete family links and calculated incidence rates of breast cancer in mothers of 48,259 daughters diagnosed with breast cancer.

Results

The risk for breast cancer in mothers of breast cancer patients is elevated relative to the background population at all ages. Mothers have an overall incidence of 0.34%/year at ages older than a daughter's age at diagnosis. This rate is not affected to any large extent by the daughter's age at diagnosis. A constant incidence rate of 0.40%/year from age 35 years onward is seen in mothers of breast cancer patients diagnosed before 35 years of age. For mothers of daughters diagnosed at age 35 to 44 years the incidence pattern is less clear, with the rate being stable for approximately 20 years after the daughter's age at diagnosis and rising thereafter. Older age at a daughter's diagnosis (≥ 45 years) appears to confer an age-dependent increase in incidence in the mother.

Conclusions

Incidence of familial breast cancer in first-degree relatives may increase to a high and constant level by a predetermined age that is specific to each family. This phenomenon appears inconsistent with accepted theories of malignant transformation.
Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure
Authors: Kneyber Martin CJ , van Heerde Marc , Twisk Jos WR , Plötz Frans B , Markhors Dick G
Published: May 2009

Introduction

Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of mechanical ventilation with heliox in these patients is unclear. The objective of this prospective cross-over study was to determine the effects of mechanical ventilation with heliox 60/40 versus conventional gas on respiratory system resistance, air-trapping and CO2 removal.

Methods

Mechanically ventilated, sedated and paralyzed infants with proven RSV were enrolled within 24 hours after paediatric intensive care unit (PICU)admission. At T = 0, respiratory system mechanics including respiratory system compliance and resistance, and peak expiratory flow rate were measured with the AVEA ventilator. The measurements were repeated at each interval (after 30 minutes of ventilation with heliox, after 30 minutes of ventilation with nitrox and again after 30 minutes of ventilation with heliox). Indices of gas exchange (ventilation and oxygenation index) were calculated at each interval. Air-trapping (defined by relative change in end-expiratory lung volume) was determined by electrical impedance tomography (EIT) at each interval.

Results

Thirteen infants were enrolled. In nine, EIT measurements were performed. Mechanical ventilation with heliox significantly decreased respiratory system resistance. This was not accompanied by an improved CO2 elimination, decreased peak expiratory flow rate or decreased end-expiratory lung volume. Importantly, oxygenation remained unaltered throughout the experimental protocol.

Conclusions

Respiratory system resistance is significantly decreased by mechanical ventilation with heliox (ISCRTN98152468).
Early drotrecogin alpha (activated) administration in severe sepsis is associated with lower mortality: a retrospective analysis of the Canadian ENHANCE cohort
Authors: Hodder Richard V , Hall Richard , Russell James A , Fisher Harold N , Lee Bobbie
Published: May 2009

Introduction

Early multimodal treatment of severe sepsis, including the use of drotrecogin alfa (activated) (DrotAA) when indicated, is considered essential for optimum outcome. However, predicting which infected patients will progress to severe sepsis and the need for aggressive intervention continues to be problematic. We therefore wished to explore whether there were any potential early markers that might predict improved survival in response to early use of DrotAA in patients with severe sepsis. In particular, in the dynamic setting of severe sepsis, we postulated that changes in markers reflecting evolving rather than baseline clinical status might guide therapy.

Methods

Data on a cohort of 305 Canadian patients from the open label ENHANCE trial of DrotAA in severe sepsis was retrospectively analyzed to search for potential clinical predictors of outcome in severe sepsis. Patients received a 96-hour infusion of DrotAA and were followed for 28 days. The association between time to treatment and mortality within subgroups defined by dynamic changes in various potential markers was explored.

Results

Mortality at 28 days was 22.6% and the variables of age, time to treatment, and early changes in serum creatinine and platelet count were identified by logistic regression as independent predictors of mortality. Across all age ranges, 28-day mortality was lower when DrotAA was administered within 24 hours of first sepsis-induced organ dysfunction compared to administration after 24 hours for both subgroups of patients defined by changes in platelet count and creatinine within the first day.

Conclusions

These findings suggest that when indicated, treatment with DrotAA should be initiated as soon as possible, regardless of age.

Trial Registration

Previous trial registration number: NCT00568893
Ethyl pyruvate decreases HMGB1 release and ameliorates murine colitis
Authors: Davé Shaival H , Tilstra Jeremy S , Matsuoka Katsuyoshi , Li Fengling , DeMarco Richard A , Beer-Stolz Donna , Sepulveda Antonia R , Fink Mitchell P , Lotze Michael T , Plevy Scott E
Published: May 2009

In two murine models of the human inflammatory bowel diseases, treatment with ethyl pyruvate ameliorated multiple features of active colitis, possibly by inhibiting expression and release of the damage-associated molecular pattern molecule HMGB1 from inflamed intestinal mucosa.

Signals from stressed cells and the enteric microbiota activate macrophages and dendritic cells and mediate intestinal inflammation. HMGB1 serves as an immunogenic stimuli causing release of inflammatory cytokines by myeloid cells. Ethyl pyruvate inhibits secretion of HMGB1 and improves survival in models of endotoxemia and hemorrhagic shock. We reasoned that ethyl pyruvate may be protective in colitis, which involves similar inflammatory pathways. In IL-10−/− mice with established chronic colitis, ethyl pyruvate administration ameliorated colitis and reduced intestinal cytokine production. IL-10−/− mice demonstrated increased intestinal HMGB1 expression and decreased expression of RAGE compared with wild-type mice. Fecal HMGB1 levels were decreased in ethyl pyruvate-treated mice. Furthermore, ethyl pyruvate induced HO-1 expression in intestinal tissue. In TNBS-induced colitis, intrarectal administration of ethyl pyruvate resulted in amelioration of colitis and reduced intestinal cytokine production. In LPS-activated murine macrophages, ethyl pyruvate decreased expression of IL-12 p40 and NO production but did not affect IL-10 levels. Ethyl pyruvate did not inhibit nuclear translocation of NF-κB family members but attenuated NF-κB DNA binding. Additionally, ethyl pyruvate induced HO-1 mRNA and protein expression and HO-1 promoter activation. Moreover, ethyl pyruvate prevented nuclear-to-cytoplasmic translocation of HMGB1. In conclusion, the HMGB1/RAGE pathway has pathophysiologic and diagnostic significance in experimental colitis. Ethyl pyruvate and other strategies to inhibit HMGB1 release and function represent promising interventions in chronic inflammatory diseases.
Aberrant TGF-β signaling reduces T regulatory cells in ICAM-1-deficient mice, increasing the inflammatory response to Mycobacterium tuberculosis
Authors: Windish Hillarie Plessner , Lin P Ling , Mattila Joshua T , Green Angela M , Onuoha Ezenwa Obi , Kane Lawrence P , Flynn JoAnne L
Published: May 2009

Uncontrolled lung pathology resulting from reduced T regulatory cells causes increased susceptibility to Mycobacterium tuberculosis in ICAM-1-deficient mice.

Foxp3+ T regulatory cells are required to prevent autoimmune disease, but also prevent clearance of some chronic infections. While natural T regulatory cells are produced in the thymus, TGF-β1 signaling combined with T-cell receptor signaling induces the expression of Foxp3 in CD4+ T cells in the periphery. We found that ICAM-1−/− mice have fewer T regulatory cells in the periphery than WT controls, due to a role for ICAM-1 in induction of Foxp3 expression in response to TGF-β1. Further investigation revealed a functional deficiency in the TGF-β1-induced translocation of phosphorylated Smad3 from the cytoplasmic compartment to the nucleus in ICAM-1-deficient mice. This impairment in the TGF-β1 signaling pathway is most likely responsible for the decrease in T regulatory cell induction in the absence of ICAM-1. We hypothesized that in the presence of an inflammatory response, reduced production of inducible T regulatory cells would be evident in ICAM-1−/− mice. Indeed, following Mycobacterium tuberculosis infection, ICAM-1−/− mice had a pronounced reduction in T regulatory cells in the lungs compared with control mice. Consequently, the effector T-cell response and inflammation were greater in the lungs of ICAM-1−/− mice, resulting in morbidity due to overwhelming pathology.
Lymphoma After Solid Organ Transplantation: Risk, Response to Therapy, and Survival at a Transplantation Center
Authors: Knight Jason S. , Tsodikov Alexander , Cibrik Diane M. , Ross Charles W. , Kaminski Mark S. , Blayney Douglas W.
Published: May 2009

Purpose

We studied the incidence, risk factors, treatment, and outcomes of post-transplantation lymphoproliferative disorder (PTLD) that occurred at the University of Michigan since 1964.

Patients and Methods

We identified 7,040 patients who received solid organ transplantation (SOT) and post-transplantation immunosuppressive therapy. Seventy-eight patients developed PTLD.

Results

Diffuse large B-cell lymphoma (n = 43), polymorphic PTLD (n = 10), Hodgkin's lymphoma (n = 7), Burkitts lymphoma (n = 6), plasmacytoma (n = 5), and mucosa-associated lymphoid tissue lymphoma (n = 3) were all over-represented in the SOT population compared with a population sample from the Surveillance, Epidemiology, and End Results (SEER) database; follicular lymphoma (n = 0) was underrepresented. Negative pretransplantation Epstein-Barr virus (EBV) serology was a risk factor for PTLD. Available histologic analysis of tumor tissue showed that 75% were CD20 positive and that 62% were EBV positive; EBV-positive tumors occurred sooner after SOT than EBV-negative tumors (mean, 29 v 66 months). Extralymphatic disease (79%), poor performance status (68%), elevated lactate dehydrogenase (LDH; 71%), and advanced stage (68%) disease were all common at the time of lymphoma diagnosis. Two thirds of patients had a complete response when treated with cyclophosphamide, doxorubicin, vincristine, and prednisone–like chemotherapy (either with or without rituximab). Median overall survival in all patients with PTLD was 8.23 years (95% CI, 2.28 to 30.0 years).

Conclusion

EBV-naïve patients who receive a donor organ from an EBV-infected donor are in the highest-risk situation for PTLD development. Most of these lymphomas are CD20 positive. Follicular lymphoma is unusual. With treatment, survival of patients with PTLD was indistinguishable from that of the SEER population sample.
Money Doctoring after World War II: Arthur I. Bloomfield and the Federal Reserve Missions to South Korea
Authors: Alacevich Michele , Asso Pier Francesco
Published: May 2009

We explore the foreign economic policy activities of Arthur I. Bloomfield, a prominent economist of the Federal Reserve Bank of New York in the 1940s and the 1950s. During the cold war, Bloomfield headed several missions to South East Asia, assisting local authorities in shaping new foreign exchange regimes and banking institutions. Bloomfield's most successful mission concerned the constitution of a new central bank in South Korea, established in June 1950.

In line with the Fed's new strategy established by Robert Triffin, head of the Latin American section, Bloomfield moved away from the dogmatic style of Edwin Kemmerer that dominated U.S. overseas missions in the first half of the twentieth century; “Southern” economies, in fact, rather than benefiting from Kemmerer's policies, had been increasingly hit by cyclical instability. According to Triffin and Bloomfield, U.S. overseas missions should loosen constraints on the activity of economic institutions and policy authorities, in order to increase their effectiveness as guarantors of financial stability and promoters of national development.

We examine this episode in the light of the U.S. postwar foreign economic relations and the concept of “embedded liberalism.” The Bloomfield missions to South Korea show with great clarity the principal features of the Fed's new foreign strategy and the need to examine the actual advisory activity of Fed economists during the 1940s: they were at the intersection between domestic and international political and economic systems. Ultimately, they played a major role in forging the actual foreign policy of the United States.
Habits and Expectations: Dynamic General Equilibrium in the Italian Paretian School
Authors: Pomini Mario , Tusset Gianfranco
Published: May 2009

Between the two world wars, the theory of general economic equilibrium received notable impetus in Italy from the work of the Paretian School. This consisted of a small, but very active, group of economists, whose best-known members at the time were Luigi Amoroso and Giulio La Volpe. One of the main aspects of the research program carried out by the followers of Pareto was their attempt to dynamize the theory of general economic equilibrium. These economists believed that research on static economics was by then complete although they were well aware that some analytical problems were still unsolved, and they advanced the construction of dynamic models using new and sophisticated mathematical tools such as functional calculus. However, despite its originality, the Paretian approach to dynamics, at least in the fields of pure theorizing, did not have a significant impact on the understanding of economic dynamics in the postwar period; we attempt to explore why.
Thomas Tooke on the Corn Laws
Authors: Smith Matthew
Published: May 2009

This article examines Thomas Tooke's (1773–1858) position on the English Corn Laws from 1815 until their repeal in 1846. It shows that like most classical economists, Tooke was a strong supporter of free trade who vehemently opposed the Corn Laws, believing that they generally contributed toward greater instability in the price of corn without effectively protecting domestic farming and securing for Britain a ready supply of corn. The article also explores Tooke's view on the distributional impact of the Corn Laws, showing that distinct from Ricardo's position, he believed they tended to redistribute income in favor of landlords at the expense of workers rather than capitalists. Indeed, it is shown that above all Tooke opposed the Corn Laws because they tended to lower the living standards of working people and, at times of unproductive harvests, contributed to acute shortages of foodstuffs that imposed much hardship onto the “lowest classes” of society.
Semaphorin signaling in cancer cells and in cells of the tumor microenvironment – two sides of a coin
Authors: Capparuccia Lorena , Tamagnone Luca
Published: May 2009

Semaphorins are a large family of secreted and membrane-bound molecules that were initially implicated in the development of the nervous system and in axon guidance. More recently, they have been found to regulate cell adhesion and motility, angiogenesis, immune responses, and tumor progression. Semaphorin receptors, the neuropilins and the plexins, are expressed by a wide variety of cell types, including endothelial cells, bone-marrow-derived cells and cancer cells. Interestingly, a growing body of evidence indicates that semaphorins also have an important role in cancer. It is now known that cancer progression, invasion and metastasis involve not only genetic changes in the tumor cells but also crosstalk between tumor cells and their surrounding non-tumor cells. Through the recruitment of endothelial cells, leukocytes, pericytes and fibroblasts, and the local release of growth factors and cytokines, the tumor microenvironment can mediate tumor-cell survival, tumor proliferation and regulation of the immune response. Moreover, by conferring cancer cells with an enhanced ability to migrate and invade adjacent tissues, extracellular regulatory signals can play a major role in the metastatic process. In this Commentary, we focus on the emerging role of semaphorins in mediating the crosstalk between tumor cells and multiple stromal cell types in the surrounding microenvironment.
Inhibitors of clathrin-dependent endocytosis enhance TGFβ signaling and responses
Authors: Chen Chun-Lin , Hou Wei-Hsien , Liu I-Hua , Hsiao George , Huang Shuan Shian , Huang Jung San
Published: May 2009

Clathrin-dependent endocytosis is believed to be involved in TGFβ-stimulated cellular responses, but the subcellular locus at which TGFβ induces signaling remains unclear. Here, we demonstrate that inhibitors of clathrin-dependent endocytosis, which are known to arrest the progression of endocytosis at coated-pit stages, inhibit internalization of cell-surface-bound TGFβ and promote colocalization and accumulation of TβR-I and SARA at the plasma membrane. These inhibitors enhance TGFβ-induced signaling and cellular responses (Smad2 phosphorylation/nuclear localization and expression of PAI-1). Dynasore, a newly identified inhibitor of dynamin GTPase activity, is one of the most potent inhibitors among those tested and, furthermore, is a potent enhancer of TGFβ. Dynasore ameliorates atherosclerosis in the aortic endothelium of hypercholesterolemic ApoE-null mice by counteracting the suppressed TGFβ responsiveness caused by the hypercholesterolemia, presumably acting through its effect on TGFβ endocytosis and signaling in vascular cells.
Role of kinesin-1 and cytoplasmic dynein in endoplasmic reticulum movement in VERO cells
Authors: Woźniak Marcin J. , Bola Becky , Brownhill Kim , Yang Yen-Ching , Levakova Vesselina , Allan Victoria J.
Published: May 2009

Generating the extended endoplasmic reticulum (ER) network depends on microtubules, which act as tracks for motor-driven ER tubule movement, generate the force to extend ER tubules by means of attachment to growing microtubule plus-ends and provide static attachment points. We have analysed ER dynamics in living VERO cells and find that most ER tubule extension is driven by microtubule motors. Surprisingly, we observe that ∼50% of rapid ER tubule movements occur in the direction of the centre of the cell, driven by cytoplasmic dynein. Inhibition of this movement leads to an accumulation of lamellar ER in the cell periphery. By expressing dominant-negative kinesin-1 constructs, we show that kinesin-1 drives ER tubule extension towards the cell periphery and that this motility is dependent on the KLC1B kinesin light chain splice form but not on KLC1D. Inhibition of kinesin-1 promotes a shift from tubular to lamellar morphology and slows down the recovery of the ER network after microtubule depolymerisation and regrowth. These observations reconcile previous conflicting studies of kinesin-1 function in ER motility in vivo. Furthermore, our data reveal that cytoplasmic dynein plays a role in ER motility in a mammalian cultured cell, demonstrating that ER motility is more complex than previously thought.
β8 integrin regulates neurogenesis and neurovascular homeostasis in the adult brain
Authors: Mobley Aaron K. , Tchaicha Jeremy H. , Shin Jaekyung , Hossain Mohammad G. , McCarty Joseph H.
Published: May 2009

Central nervous system (CNS) neurovascular units are multicellular complexes consisting of neural cells, blood vessels and a milieu of extracellular matrix (ECM) proteins. ECM-mediated adhesion and signaling events within neurovascular units probably contribute to proper CNS development and physiology; however, the molecular mechanisms that control these events remain largely undetermined. Previous studies from our group and others showed that ablation of the ECM receptor, αvβ8 integrin, in neural progenitor cells (NPCs) of the embryonic mouse brain results in severe developmental neurovascular pathologies and premature death. Here, we have investigated the functions for this integrin in the adult brain by studying mice harboring a homozygous-null β8 gene mutation generated on an outbred background that permits survival for several months. We show that adult β8–/– mice display widespread defects in neurovascular unit homeostasis, including increased numbers of intracerebral blood vessels with pronounced perivascular astrogliosis. Furthermore, in neurogenic regions of the adult brain, where NPCs cluster around blood vessels in neurovascular niches, β8 integrin is essential for normal control of NPC proliferation and survival. Analysis of NPCs cultured ex vivo reveals that the growth and survival defects correlate, in part, with diminished integrin-mediated activation of latent transforming growth factor β1 (TGFβ1), which is an ECM protein ligand for αvβ8 integrin. Collectively, these data identify essential functions for β8 integrin in regulating neurovascular unit physiology in the post-natal mouse brain.
Blocking β-catenin binding to the ZBP1 promoter represses ZBP1 expression, leading to increased proliferation and migration of metastatic breast-cancer cells
Authors: Gu Wei , Pan Feng , Singer Robert H.
Published: May 2009

ZBP1 (zipcode-binding protein 1, also known as IMP-1) is an mRNA regulator, functioning in mRNA localization, stability and translational control. ZBP1 is actively expressed during embryogenesis and tumorigenesis, but its expression is repressed in metastatic breast-cancer cell lines and tumors. In this article, we show that downregulation of ZBP1 expression results from its promoter methylation, an epigenetic process that remodels the chromatin structure and frequently represses gene activity. Demethylation of the ZBP1 promoter in metastatic cells reactivated ZBP1 expression, owing to restoration of the interaction of the ZBP1 promoter with β-catenin. Loss of ZBP1 function not only increased growth ability of metastatic cells, but also promoted cell migration. We identified a number of mRNAs that were selectively associated with ZBP1 in breast-cancer cells. Many of these are involved in cell motility and in cell-cycle regulation, and displayed altered expression patterns in the absence of ZBP1. These data suggest that repression of ZBP1 deregulates its associated mRNAs, leading to the phenotypic changes of breast cancers.
Comparison of blood glucose meters in a New Zealand diabetes centre
Authors: Florkowski Christopher , Budgen Christopher , Kendall Deborah , Lunt Helen , Moore M Peter
Published: May 2009

Background

To assess the accuracy and precision of the Roche Performa and Medisense Optium Xceed (5 and 10 s reading) blood glucose meters.

Methods

Capillary blood samples were taken from 100 patients attending a diabetes centre and blood glucose measured on Roche Performa ( n = 4) and Medisense Optium Xceed 5 s ( n = 2) and 10 s reading ( n = 2) meters. Venous plasma glucose from samples taken simultaneously was measured by the laboratory hexokinase method as reference standard. Imprecision was determined on the meters by replicate analysis ( n = 20) of control solutions provided by the manufacturers and also patient venous whole-blood samples. Accuracy was assessed relative to the reference method by Bland–Altman plots, Passing and Bablok regression analysis, and both Clarke and consensus error grid analysis. Coefficients of variation (CVs) were calculated to determine imprecision.

Results

Bland–Altman and Passing–Bablok analysis confirmed significant systematic bias for all meters, with relative under-reading of higher glucose concentrations. Error grid analysis showed that <5% readings exceeded ±20% (or ±0.83 mmol/L for readings <4 mmol/L) deviation from the reference method (1%, 2% and 4% for the Roche, Optium 5 and 10 s meters, respectively). CVs were all <4% for the control solutions and <6% for patient samples.

Conclusions

Both Roche Performa and Medisense Optium glucose meters (5 and 10 s readings) perform satisfactorily and are acceptable for operational use.
Haemodialysis patients longitudinally assessed by highly sensitive cardiac troponin T and commercial cardiac troponin T and cardiac troponin I assays
Authors: Jacobs Leo H , van de Kerkhof Jos , Mingels Alma M , Kleijnen Vincent W , van der Sande Frank M , Wodzig Will K , Kooman Jeroen P , van Dieijen-Visser Marja P
Published: May 2009

Background

Elevated cardiac troponin (cTn) concentrations predict an increased mortality in patients suffering from end-stage renal disease (ESRD). This study compares the performance of a precommercial high-sensitive cTnT assay (hs-cTnT) with two contemporary cTn assays in detecting cTn elevations in ESRD patients during a six-month follow-up.

Methods

Thirty-two ESRD patients were followed for six months, during which cTn concentrations were assessed every two months. Baseline biomarker concentrations were compared with those in a simultaneously measured reference population of 501 healthy subjects.

Results

During follow-up 26 (81%), 32 (100%) and 9 (28%) of the patients showed elevated cTn concentrations according to the current cTnT, the hs-cTnT and the cTnI assays, respectively. The range of concentrations measured in each patient had a median (interquartile range) magnitude of 0.03 μg/L (0.02–0.06), 0.017 μg/L (0.011–0.029) and 0.011 μg/L (0–0.017) according to the aforementioned assays.

Conclusion

According to the hs-cTnT assay, all of the ESRD patients had elevated cTnT concentrations at least once during the follow-up. As elevated cTn concentrations are highly prognostic of adverse events, the use of serial measurements has thus identified additional patients at risk for such events. The fact that we find cTn concentrations to be higher in patients with a history of cardiac disease is in line with this. Additional studies in ESRD patients are needed to investigate the added diagnostic and prognostic value of the very low cTnT concentrations and variations detected only by the hs-cTnT assay.
Differentially displayed proteins as a tool for the development of type 2 diabetes
Authors: Dincer Ayse , Onal Secil , Timur Suna , Zeytunluoglu Ali , Duman Erdal , Zihnioglu Figen
Published: May 2009

Background

Type 2 diabetes is a complex disease that still requires a great deal of work to be carried out to understand the pathophysiology. Recently, researchers have focused on studying the organs and tissues known to be involved in the development of the type 2 phenotype using a proteomic approach. Little work has been reported on plasma of type 2 diabetics in whom the clinical status has been well characterized. In this study, changes in plasma proteins of type 2 diabetics were investigated by proteomic analysis in well-characterized individuals with type 2 diabetes (early and late stage) and control groups (with or without a family history of diabetes).

Methods

Samples were analysed by two-dimensional gel electrophoresis and significantly differentiated proteins were identified by nano-LC-ESI-MS.

Results

A total of 12 protein signatures that were differentially displayed with high significance compared with controls were selected. Four of the differentially displayed proteins were identified as haptoglobin alpha2, haptoglobin Hp2(fragment) and transthyretin and Chain A (formerly prealbumin), and all were up-regulated. Thiol-specific antioxidant protein, Chain A, tertiary structures of three amyloidogenic transthretin variants and haptoglobin-related protein precursor were all down-regulated in controls with a family history of diabetes, early and late diabetic patients in comparison with the control.

Conclusion

A proteomic-based approach was used to discover and identify the differentially expressed proteins in various states of type 2 diabetes.
Exact Algorithms for the Quadratic Linear Ordering Problem
Authors: Buchheim Christoph , Wiegele Angelika , Zheng Lanbo
Published: May 2009

The quadratic linear ordering problem naturally generalizes various optimization problems such as bipartite crossing minimization or the betweenness problem, which includes linear arrangement. These problems have important applications, e.g., in automatic graph drawing and computational biology. We present a new polyhedral approach to the quadratic linear ordering problem that is based on a linearization of the quadratic objective function.

Our main result is a reformulation of the 3-dicycle inequalities using quadratic terms. After linearization, the resulting constraints are shown to be face-inducing for the polytope corresponding to the unconstrained quadratic problem. We use this result both within a branch-and-cut algorithm and within a branch-and-bound algorithm based on semidefinite programming. Experimental results for bipartite crossing minimization show that this approach clearly outperforms other methods.
Setting the Research Agenda in Automated Timetabling: The Second International Timetabling Competition
Authors: McCollum Barry , Schaerf Andrea , Paechter Ben , McMullan Paul , Lewis Rhyd , Parkes Andrew J. , Gaspero Luca Di , Qu Rong , Burke Edmund K.
Published: May 2009

The Second International Timetabling Competition (TTC2007) opened in August 2007. Building on the success of the first competition in 2002, this sequel aimed to further develop research activity in the area of educational timetabling. The broad aim of the competition was to create better understanding between researchers and practitioners by allowing emerging techniques to be developed and tested on real-world models of timetabling problems. To support this, a primary goal was to provide researchers with models of problems faced by practitioners through incorporating a significant number of real-world constraints. Another objective of the competition was to stimulate debate within the widening timetabling research community. The competition was divided into three tracks to reflect the important variations that exist in educational timetabling within higher education. Because these formulations incorporate an increased number of “real-world” issues, it is anticipated that the competition will now set the research agenda within the field. After finishing in January 2008, final results were made available in May 2008. Along with background to the competition, the competition tracks are described here along with a brief overview of the techniques used by the competition winners.
Information Provision in a Vertically Differentiated Competitive Marketplace
Authors: Kuksov Dmitri , Lin Yuanfang
Published: May 2009

This paper examines the interaction of information provision, product quality, and pricing decisions by competitive firms to explore the following question: in a competitive market where consumers face uncertainty about product quality and/or their preference for quality, which firms—those that sell higher- or lower-quality products—have the higher incentive to provide what type of information? We find that while the higher-quality firm should always provide information resolving consumer uncertainty on product quality, the lower-quality firm under certain conditions will have the higher incentive to and will be the one to provide information resolving consumer uncertainty about their quality preferences. In the analysis, we trace the latter result to competition and to free-riding on the information provision. Specifically, in a monopoly market or when consumer free-riding is restricted by the costliness of store visits, the lower-quality firm would have a lower incentive to provide information resolving consumer preference uncertainty than otherwise. The model is also adapted to examine product returns as a possible strategy of information provision.
Empirical Analysis of Metering Price Discrimination: Evidence from Concession Sales at Movie Theaters
Authors: Gil Ricard , Hartmann Wesley R.
Published: May 2009

Prices for goods such as blades for razors, ink for printers, and concessions at movies are often set well above cost. Theory has shown that this could yield a profitable price discrimination strategy often termed “metering.” The idea is that a customer's intensity of demand for aftermarket goods (e.g., the concessions) provides a meter of how much the customer is willing to pay for the primary good (e.g., admission). If this correlation in tastes for the two goods is positive, a high price on the aftermarket good allows firms to extract a greater total price (admissions plus concessions) from higher-type customers. This paper develops a simple aggregate model of discrete-continuous demand to motivate how this correlation can be tested using simple regression techniques and readily available firm data. Model simulations illustrate that the regressions can be used to predict whether aftermarket prices should be above, below, or equal to their marginal cost. We then apply the approach to box office and concession data from a chain of Spanish theaters and find that high-priced concessions do extract more surplus from customers with a greater willingness to pay for the admission ticket.
Assessment of Platelet Function on Whole Blood by Multiple Electrode Aggregometry in High-Risk Patients With Coronary Artery Disease Receiving Antiplatelet Therapy
Authors: Paniccia Rita , Antonucci Emilia , Maggini Niccolò , Romano Eloisa , Gori Anna Maria , Marcucci Rossella , Prisco Domenico , Abbate Rosanna
Published: May 2009

This study sought to compare Multiplate impedance platelet aggregometry (IPA) with light transmission aggregometry (LTA) and the PFA-100 for determining the prevalence of residual platelet reactivity (RPR) by the Multiplate IPA in 297 patients with acute coronary syndrome receiving dual antiplatelet therapy. Aggregations were induced by adenosine-5 diphosphate (ADP), arachidonic acid, and collagen. PFA-100 closure times were measured by collagen and ADP and epinephrine (CEPI) cartridges. Significant correlations were observed between Multiplate IPA and LTA after all stimulations (P < .0001) and between Multiplate IPA (arachidonate and collagen) and PFA-100 CEPI closure time (P < .0001 for both). Cutoff values of Multiplate IPA (for all stimulations) were calculated for the identification of RPR. Between the Multiplate IPA and LTA good agreement was found with all 3 agonists (P < .0001 for all). Multiplate IPA might represent a reliable, handy, rapid tool to monitor antiplatelet therapy in clinical practice and for clinical investigations.
The Effect of Argatroban on Activated Protein C Resistance
Authors: Shaikh Salima , Van Cott Elizabeth M.
Published: May 2009

Activated protein C (APC) resistance is commonly tested in hypercoagulation evaluations, and argatroban is an anticoagulant therapy used in hypercoagulable patients. The effect of argatroban on APC resistance testing is unknown. We studied 100 ex vivo specimens from 44 patients treated with argatroban. Argatroban increased the APC resistance ratio in all but 1 patient. The effect was seen even in the specimens containing subtherapeutic argatroban levels. For patients without APC resistance, the mean APC resistance ratio significantly increased from 2.43 without argatroban to 3.10 with argatroban. For patients with APC resistance due to factor V Leiden, argatroban significantly increased the mean ratio from 1.73 to 2.13, falsely raising it into the normal range (>2). Argatroban increases the APC resistance ratio, which can mask a diagnosis of APC resistance and, therefore, factor V Leiden. Clinicians should be advised that APC resistance testing for patients receiving argatroban is not valid.
Effect of Soy Extract Administration on Losartan Pharmacokinetics in Healthy Female Volunteers
Authors: Wang Guo , Xiao Chang-Qiong , Li Zhi , Guo Dong , Chen Yao , Fan Lan , Qian Rong-Hua , Peng Xiu-Juan , Hu Dong-Li , Zhou Hong-Hao
Published: May 2009

Background

Losartan is metabolized by CYP2C9 and CYP3A4 to an active metabolite, E-3174, which has greater antihypertensive activity than the parent compound. Soy extract has been shown to be an activator of CYP2C9 and CYP3A4 in vitro. Coadministration of soy extract and losartan may therefore after the pharmacokinetics of losartan and E-3174.

Objective

To determine whether, when losartan was used in combination with soy extract, a significant pharmacokinetic interaction would be observed in healthy female volunteers.

Methods

Eighteen healthy Chinese female volunteers were recruited. In an open-label, 2-phase study, losartan 50 mg was given to each subject, with and without soy extract. Plasma concentrations of losartan and E-3174 were determined by liquid chromatography–tandem mass spectrometry for 12 and 24 hours, respectively. On day 8 through day 21 of the study, following a 7-day washout period, each subject consumed two 1000-mg Genistein Soy Complex tablets orally after meals, twice daily, for 14 days. On day 22, all volunteers received losartan 50 mg and blood samples were collected again.

Results

All subjects completed the study, without adverse drug effects. Over the 14-day pretreatment period, soy extract did not significantly influence the pharmacokinetics of losartan or E-3174. The ratio of the area under the curve of the drug and metabolite after losartan administration, with and without soy extract ingestion, was 0.21 ± 0.05 and 0.23 ± 0.05 (mean ± SD), respectively. The difference was not statistically significant (p = 0.22).

Conclusions

Our data indicate that a significant interaction between soy extract and losartan is unlikely to occur in females.
Swelling behavior of Na- and Ca-montmorillonite up to 150°C by in situ X-Ray diffraction experiments
Authors: Morodome Shoji , Kawamura Katsuyuki
Published: May 2009

The effects of temperature on the swelling properties of smectites are important for a variety of different geological conditions, but studies on this topic have been rather limited. The purpose of this study was to investigate the swelling behavior of Na- and Ca-montmorillonite at various temperatures greater than room temperature, up to 150°C, using in situ X-ray diffraction (XRD) analysis. A sample chamber was designed, the temperature and humidity of which were controlled precisely, for environmental in situ measurements. The XRD measurements were performed at small relative humidity (RH) intervals for precise observation of the swelling behavior.

The swelling behavior of Na-montmorillonite showed distinct zero-, one-, and two-layer hydration states. The basal spacings of Na-montmorillonite changed continuously with RH for various temperatures in the transition region between the zero- and one-layer hydration states, and the swelling curves of the transition region moved to greater degrees of RH with increasing temperature. The basal spacings jumped from the one- to two-layer hydration states for all temperatures at almost the same RH.

The basal spacings of Ca-montmorillonite changed continuously from the zero- to the two-layer hydration states at all temperatures. This behavior is remarkably different from that of Na-montmorillonite. At low-RH conditions, the d001 value of Ca-montmorillonite decreased with increasing temperature. The swelling curves of Ca-montmorillonite did not show a plateau at any temperature for the one-layer hydration state. The swelling curves of Ca-montmorillonite moved to greater RH with temperature, similar to the transformation region between the zero- and one-layer hydration states in Na-montmorillonite. These differences between Na- and Ca-montmorillonite are related to the hydration powers of exchangeable cations.
Interlayer conformations of intercalated dodecyltrimethylammonium in rectorite as determined by FTIR, XRD, and TG analyses
Authors: Li Zhaohui , Jiang Wei-Teh
Published: May 2009

Intercalation of a wide variety of alkylammonium cations into the interlayer spaces of swelling clay minerals leads to many different applications, ranging from surface-charge measurements to rendering the clay compatible for the preparation of clay nanocomposites, but knowledge of the exact conformation of the intercalated organic species is still incomplete, thus preventing a full understanding of this process. The purpose of this study was to investigate the interlayer conformation of dodecyltrimethylammonium (DDTMA) bromide in rectorite as affected by the amounts of DDTMA intercalated, using a battery of physical and spectroscopic methods. The capacity of rectorite to intercalate DDTMA was equivalent to 1.67 times the cation exchange capacity (1.67 CEC) of the mineral even though the initial input was as much as 5.00 CEC. When the DDTMA intercalated was <0.50 CEC of the mineral, minimal counterion sorption was associated with DDTMA intercalation. Derivative thermogravimetric (DTG) analyses revealed a single-peak decomposition temperature (Tpeak) at 430°C. X-ray diffraction (XRD) analyses indicated a flat-lying monolayer of the intercalated molecules, while shifts in Fourier Transform infrared (FTIR) bands confirmed gauche conformation. These results suggested that cation exchange was the dominant mechanism. At the maximum intercalation, the DDTMA adopted a horizontal trilayer arrangement with mainly gauche conformation as determined by FTIR and XRD. Meanwhile a second Tpeak appeared at 255°C, similar to the Tpeak of solid DDTMA. Counterion bromide sorption accompanying DDTMA intercalation reached a capacity of 310 mmol/kg. The results indicated that van der Waals interaction was responsible for the DDTMA uptake at the amount beyond 0.50 CEC. When the amount of DDTMA intercalated was between 0.5 and 1.67 CEC, the XRD patterns showed non-integrality, i.e. the 002 reflection was split into two non-integral peaks with 2 × d002 < d001 and 3 × d003 > d001. They became integral at 1.67 CEC. The results suggest that the mineral might be composed of mixed layers of a monolayer intercalated rectorite and a trilayer intercalated rectorite, without a bilayer as intermediate, when the amount of DDTMA intercalated was between 0.5 and 1.67 CEC.
Bacteria-clay interaction: Structural changes in smectite induced during biofilm formation
Authors: Alimova Alexandra , Katz A. , Steiner Nicholas , Rudolph Elizabeth , Wei Hui , Steiner Jeffrey C. , Gottlieb Paul
Published: May 2009

Bacteria play an important role in determining the properties and behavior of clay minerals in natural environments and such interactions have great potential for creating stable biofilms and carbon storage sites in soils, but our knowledge of these interactions are far from complete. The purpose of this study was to understand better the effects of bacteria-generated biofilms on clay interlayer expansion. Mixtures of a colloidal, 2-water hectorite clay and Pseudomonas syringae in a minimal media suspension evolve into a polysaccharide-rich biofilm aggregate in time-series experiments lasting up to 1 week. X-ray diffraction analysis reveals that upon aggregation, the clay undergoes an initial interlayer contraction. Short-duration experiments, up to 72 h, result in a decrease in the d001 value from 1.50 to 1.26 nm. The initial interlayer contraction is followed in long-duration (up to 1 week) experiments by an expansion of the d001 value of 1.84 nm. The expansion is probably a result of large, biofilm-produced, polymeric molecules being emplaced in the interlayer site. The resultant organo-clay could provide a possible storage medium for carbon in a microbial colony setting.
Development and validation of the Supervisory Relationship Questionnaire (SRQ) in UK trainee clinical psychologists
Authors: Palomo Marina , Beinart Helen , Cooper Myra J.
Published: May 2009

Objective. To develop a valid and reliable measure of the supervisory relationship (SR) from the supervisee perspective.

Design. A cross‐sectional questionnaire design was used with a repeated measures component for a sub‐sample.

Method. Qualitative data obtained from a previous study and from review of the literature were used to construct a 111 item self‐report questionnaire measure [Supervisory Relationship Questionnaire (SRQ)]. This was administered to 284 British trainee clinical psychologists. Eighty‐five participants completed the SRQ a second time to establish its test–retest reliability.

Results. Principal components analysis (PCA) identified six components of the SRQ. Three of these reflected the ‘facilitative’ relationship characteristics of the SR and were labelled ‘safe base’, ‘commitment’ and ‘structure’. The second set of components reflected the educative and evaluative functions of supervision. These were labelled ‘reflective education’, ‘role model’ and ‘formative feedback’. Safe base accounted for the greatest proportion of variance in SRQ scores (52 per cent). Analyses using the six subscales subsequently derived from the PCA, revealed the SRQ to have high internal reliability, good test–retest reliability and good construct (convergent and divergent) validity. A preliminary test of predictive validity was conducted.

Conclusions. The SRQ (six subscales, total of 67 items) is a valid and reliable measure of the SR from the supervisee perspective. The present findings support existing models of the SR, and its distinct nature during training as an educative and evaluative process. The SRQ is a promising tool for further research, and is likely to be useful in supervisor training and clinical settings.
Establishment of Joint Attention in Dyads Involving Hearing Mothers of Deaf and Hearing Children, and Its Relation to Adaptive Social Behavior
Authors: Nowakowski Matilda E. , Tasker Susan L. , Schmidt Louis A.
Published: May 2009

Mounting evidence points to joint attention as a mediating variable in children's adaptive behavior development. Joint attention in interactions between hearing mothers and congenitally deaf ( n = 27) and hearing ( n = 29) children, ages 18–36 months, was examined. All deaf children had severe to profound hearing loss. Mother-child interactions were coded for maternally initiated and child-initiated success rates in establishing joint attention; mothers completed ratings of their children's adaptive behavior. Hearing mother–deaf child dyads had significantly lower maternally initiated success rates. No significant between-group differences on child-initiated success rates were shown. Maternal ratings of adaptive behavior were significantly lower for deaf children, and related positively and significantly to both child-initiated and maternally initiated success rates. The findings suggest that mother-child interactions that are low in successful establishment of joint attention might mediate the development of socioemotional problems evident in deaf children with hearing families.