bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethics and law teaching and learning in undergraduate medicine
Authors: Sutton A
Published: July 2010

The updated consensus report on undergraduate medical education (1) provides an extensive framework for teaching ethics and law. However, there is a need for further research into the indicators of good progress towards sound moral reasoning and action to take into account personal and professional developmental trajectories. The report indicates competencies which should be demonstrable by students: additional consideration needs to be given to those competencies which institutions should be able to demonstrate in relation to the provision made for students and teachers.
Looking beyond stereoscopic 3D's revival
Authors: Kroeker Kirk L.
Published: July 2010

Researchers working in vision and graphics are attempting to develop new techniques and technologies to overcome the current limitations in stereoscopic 3D.
A Cross-Sectional Survey on Parasites of Chickens in Selected Villages in the Subhumid Zones of South-Eastern Nigeria
Authors: Nnadi P. A. , George S. O.
Published: July 2010

A study was carried out to identify and estimate the prevalence of ecto- and endoparasites of village chicken between April and July 2008 in three local councils of Enugu state, Nigeria. A total of 1038 chickens comprising of 468 chicks, 207 growers and 363 adults were examined during the house to house survey for ectoparasites, gastrointestinal helminths and coccidia infections. Our finding showed that 41% were infected with ectoparasites with lice, fleas, and mites having prevalence rates of 62.2%, 35.7% and 2.1%, respectively. Helminths and coccidia had prevalence of 35.5% each. Among the helminthsAscaridia, galliwas the most dominant species (17.2%). Generally, there was a significantly higher helminth infestation relative to the ectoparasites (), high prevalence of mixed infections and absence of tick infestation. Parasitism could be big constraint to production in the study area and we recommend a sustainable control strategy.
Study of Radiative Defects Using Current‐Voltage Characteristics in ZnO Rods Catalytically Grown on 4H‐p‐SiC
Authors: Bano N. , Hussain I. , Nur O. , Willander M. , Klason P.
Published: July 2010

High‐quality ZnO rods were grown by the vapour‐liquid‐solid (VLS) technique on 4H‐p‐SiC substrate. The current transport mechanisms of the diodes at room temperature (RT) have been explained in term of the space‐charge‐limited current model based on the energy band diagram of ZnO rods/4H‐p‐SiC heterostructure. The tunneling mechanism via deep‐level states was found to be the main conduction process at low‐applied voltage but at trap‐filled limit voltage VTFL all traps are filled and the space‐charge‐limited current conduction dominated the current transport. From the RT current voltage measurements, the energy of the deep level trap and the trap concentration were obtained as ~0.24 ± 0.02 eV and 4.4 × 1018cm−3, respectively. The deep level states observed correspond to zinc interstitial (Zni
), responsible for the violet emission.
Specificity of Methylation Assays in Cancer Research: A Guideline for Designing Primers and Probes
Authors: Barekati Zeinab , Radpour Ramin , Kohler Corina , Zhong Xiao Yan
Published: July 2010

DNA methylation is an epigenetic regulation mechanism of genomic function, and aberrant methylation pattern has been found to be a common event in many diseases and human cancers. A large number of cancer studies have been focused on identification of methylation changes as biomarkers (i.e., breast cancer). However, still clinical use of them is very limited because of lack of specificity and sensitivity for diagnostic test. This highlights the critical need for specific primer and probe design to avoid false‐positive detection of methylation profiling. The guideline and online web tools that are introduced in this paper might help to perform a successful experiment and to develop specific diagnosis biomarkers by designing right primer pair and probe prior to experimental step.
A Combination of DR5 Agonistic Monoclonal Antibody with Gemcitabine Targets Pancreatic Cancer Stem Cells and Results in Long-term Disease Control in Human Pancreatic Cancer Model
Authors: Rajeshkumar N.V. , Rasheed Zeshaan A. , García-García Elena , López-Ríos Fernando , Fujiwara Kosaku , Matsui William H. , Hidalgo Manuel
Published: July 2010

Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignancy with one of the worst outcomes among all cancers. PDA often recurs after initial treatment to result in patient death despite the use of chemotherapy or radiation therapy. PDA contains a subset of tumor-initiating cells capable of extensive self-renewal known as cancer stem cells (CSC), which may contribute to therapeutic resistance and metastasis. At present, conventional chemotherapy and radiotherapy are largely ineffective in depleting CSC pool, suggesting the need for novel therapies that specifically target the cancer-sustaining stem cells for tumor eradication and to improve the poor prognosis of PDA patients. In this study, we report that death receptor 5 (DR5) is enriched in pancreatic CSCs compared with the bulk of the tumor cells. Treating a collection of freshly generated patient-derived PDA xenografts with gemcitabine, the first-line chemotherapeutic agent for PDA, is initially effective in reducing tumor size, but largely ineffective in diminishing the CSC populations, and eventually culminated in tumor relapse. However, a combination of tigatuzumab, a fully humanized DR5 agonist monoclonal antibody, with gemcitabine proved to be more efficacious by providing a double hit to kill both CSCs and bulk tumor cells. The combination therapy produced remarkable reduction in pancreatic CSCs, tumor remissions, and significant improvements in time to tumor progression in a model that is considered more difficult to treat. These data provide the rationale to explore the DR5-directed therapies in combination with chemotherapy as a therapeutic option to improve the current standard of care for pancreatic cancer patients. Mol Cancer Ther; 9(9); 2582–92. ©2010 AACR.
Triethylenetetramine Pharmacology and Its Clinical Applications
Authors: Lu Jun
Published: July 2010

Triethylenetetramine (TETA), a CuII-selective chelator, is commonly used for the treatment of Wilson's disease. Recently, it has been shown that TETA can be used in the treatment of cancer because it possesses telomerase inhibiting and anti-angiogenesis properties. Although TETA has been used in the treatment of Wilson's disease for decades, a comprehensive review on TETA pharmacology does not exist. TETA is poorly absorbed with a bioavailability of 8 to 30%. It is widely distributed in tissues with relatively high concentrations measured in liver, heart, and kidney. It is mainly metabolized via acetylation, and two major acetylated metabolites exist in human serum and urine. It is mainly excreted in urine as the unchanged parent drug and two acetylated metabolites. It has a relatively short half-life (2 to 4 hours) in humans. The most recent discoveries in TETA pharmacology show that the major pharmacokinetic parameters are not associated with the acetylation phenotype of N-acetyltransferase 2, the traditionally regarded drug acetylation enzyme, and the TETA-metabolizing enzyme is actually spermidine/spermine acetyltransferase. This review also covers the current preclinical and clinical application of TETA. A much needed overview and up-to-date information on TETA pharmacology is provided for clinicians or cancer researchers who intend to embark on cancer clinical trials using TETA or its close structural analogs. Mol Cancer Ther; 9(9); 2458–67. ©2010 AACR.
Mitochondrial DNA Mutation in Normal Margins and Tumors of Recurrent Head and Neck Squamous Cell Carcinoma Patients
Authors: Dasgupta Santanu , Koch Rachel , Westra William H. , Califano Joseph A. , Ha Patrick K. , Sidransky David , Koch Wayne M.
Published: July 2010

Mitochondrial DNA (mtDNA) mutations were reported in primary head and neck squamous cell carcinoma (HNSCC) patients. However, very little information is available on the mtDNA mutation pattern in the histologically negative surgical margins and tumors of HNSCC patients who experienced tumor recurrence. The present study aimed at understanding the nature and timing of mtDNA mutation in histologically negative margins, and tumors in HNSCC patients who developed local recurrence during the follow-ups. The entire 16.5-kb mitochondrial genome was sequenced in matched normal lymphocytes, histologically normal margins, and tumors of 50 recurrent HNSCC patients. The mtDNA mutations were then compared with clinical parameters. Forty-eight percent (24 of 50) of patients harbored at least one somatic mtDNA mutation in the tumor, and a total of 37 somatic mtDNA mutations were detected. The mtDNA mutations were mostly heteroplasmic in nature and nucleotide transitions (A↔G; T↔C). Forty-six percent of the mutations (17 of 37) were detected in the tumors and were also detectable in the corresponding histologically normal margin of the patients. The mtDNA mutations involved both coding and noncoding regions of the mtDNA. The majority (9 of 17, 53%) of the noncoding mutations involved tRNAs. Seventy-five percent (15 of 20) of the coding mtDNA mutations were nonsynonymous in nature and mainly affected cytochrome c oxidase (Complex IV), frequently altered in different human mitochondrial diseases including cancer. Analysis of mtDNA mutation could be an invaluable tool for molecular assessment of histologically negative margins and as well for monitoring HNSCC patients with locoregional recurrences. Cancer Prev Res; 3(9); 1205–11. ©2010 AACR.
Paraoxonase 1 Polymorphisms 172T→A and 584A→G Modify the Association between Serum Concentrations of the Antioxidant Lycopene and Bone Turnover Markers and Oxidative Stress Parameters in Women 25–70 Years of Age
Authors: Mackinnon E.S. , El-Sohemy A. , Rao A.V. , Rao L.G.
Published: July 2010

Background/Aims: Polymorphisms of the paraoxonase 1 (PON1) enzyme affect the ability to protect LDL from oxidation. Oxidative stress is a risk factor for osteoporosis and antioxidants may be beneficial for prevention. The aim of this study was to determine whether PON1 genotypes modified the association between lycopene and bone turnover markers and oxidative stress parameters. Methods: Blood samples from 107 women 25–70 years of age were analyzed for serum carotenoid concentrations, bone-specific alkaline phosphatase (BAP), N-telopeptide of type I collagen (NTx) and oxidative stress parameters. Subjects were genotyped for the 172T→A and 584A→G polymorphisms of PON1. Results: The 172T→A polymorphism modified the association between lycopene and NTx (p < 0.05 for interaction). In the 172TT genotype, high serum lycopene was associated with decreased NTx (p < 0.05). The 584A→G polymorphism modified the association between lycopene and BAP (p < 0.05 for interaction). Additionally, in participants with the 584GG genotype, high serum lycopene was associated with high TBA-reactive substances (p < 0.05). Conclusions: These findings show that PON1 polymorphisms modify the association between serum concentrations of lycopene and oxidative stress parameters and bone turnover markers and may, therefore, moderate the risk of osteoporosis.
Racial and Gender Differences in Arteriovenous Fistula Use among Incident Hemodialysis Patients
Authors: Wasse Haimanot , Hopson Sari D. , McClellan William
Published: July 2010

Background: Arteriovenous fistula (AVF) use is reported to differ among racial and gender groups. We sought to identify risk factors associated with incident AVF and whether racial and gender differences in AVF use persist after controlling for these factors. Methods: We evaluated 28,712 incident adult hemodialysis patients (age ≧18) from five ESRD networks starting dialysis between June 1, 2005 and May 31, 2006. Data were obtained from the Center for Medicaid and Medicare Services 2728 form. Results: Incident AVF use was reported for 11% of black and 12% of white patients [OR = 0.89 (95% CI: 0.83, 0.96)], and for 9% of females and 13% of males [OR = 0.66 (0.62–0.71)]. After adjusting for facility clustering, blacks were as likely as whites to use an AVF [OR = 1.00 (0.92–1.09)], while gender differences persisted [OR = 0.64 (0.59–0.69)]. Compared to patients with no renal care prior to dialysis initiation, incident AVF use was 16-fold greater among those with ≧12 months of nephrology care [OR = 15.99 (13.25–19.29)], 9-fold greater among those with 6–12 months of care [OR = 9.00 (7.45–10.88)] and 7-fold greater among those with at least 6 months of care [OR = 7.13 (5.73–8.88)]. Conclusion: Racial, but not gender, differences in incident AVF use were eliminated after accounting for clustering within facilities.
Collaboration between Allergists and Pharmacists Increases β-Lactam Antibiotic Prescriptions in Patients with a History of Penicillin Allergy
Authors: Park Miguel A. , McClimon Brad J. , Ferguson Brent , Markus Patricia J. , Odell Laura , Swanson Andrea , Kloos-Olson Kristin E. , Bjerke Peter F. , Li James T.
Published: July 2010

Background: Over 90% of patients with a history of penicillin allergy have negative penicillin skin tests. Pharmacists are trained to identify and resolve medication-related problems. We hypothesized that collaboration between allergists and pharmacists to identify and evaluate patients with a history of penicillin allergy would increase β-lactam antibiotic prescription. Methods: We conducted a prospective observational study in which patients with a history of penicillin allergy were identified and educated at the pharmacy about penicillin allergy and offered an allergist consultation with a penicillin skin test. All patients were followed up to determine which antibiotics were subsequently prescribed. Results: A total of 503 patients were enrolled, and 71 (14%) were evaluated by an allergist. Sixty-seven of these 71 patients (94%) had a negative penicillin skin test. Twenty-nine patients evaluated by an allergist and 205 patients not evaluated were prescribed antibiotics. Patients prescribed antibiotics and evaluated by an allergist were compared to those not evaluated by an allergist, with the following results: 19 of 29 patients (66%) were prescribed a β-lactam antibiotic compared to 54 of 205 (26%; p < 0.0001); 8 of 29 patients (28%) were prescribed penicillin compared to 7 of 205 (3%; p < 0.0001); 15 of 29 patients (52%) were prescribed a cephalosporin compared to 48 of 205 (23%; p < 0.01), and 10 of 29 patients (34%) were prescribed a non-β-lactam antibiotic compared with 177 of 205 (86%; p < 0.0001). Conclusion: A collaborative effort between allergists and pharmacists can increase β-lactam antibiotic prescriptions and decrease non-β-lactam prescriptions in patients with a history of penicillin allergy.
Hereditary Angioedema: Long-Term Treatment with One or More Injections of C1 Inhibitor Concentrate per Week
Authors: Bork Konrad , Hardt Jochen
Published: July 2010

Background: Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) is characterized by recurrent edema attacks in various organs. The objective of the present study was to assess the efficacy and safety of weekly long-term replacement treatment with one or more injections of plasma-derived C1-INH concentrate per week (WLTC) in patients with HAE-C1-INH. Methods: Nineteen patients with HAE-C1-INH underwent WLTC for 9 years on average. The benefits and risks were determined based on regular recording by the patients of the severity and number of attacks at the beginning and the end of the study. Results: All patients reported that all or most of their attacks were much less severe: the percentage of severe attacks was 93.3% without and 3.8% with treatment. In 8 of the 14 patients undergoing WLTC, the monthly number of attacks was lower at the end of the study than before the study, higher in 5 patients, and unchanged in 1 patient. The mean number of attacks per week in 6 patients (1 patient initially received weekly on-demand treatment for 2 years and then shifted to WLTC) with weekly on-demand treatment was 4.3 (SD 1.9) at the beginning and 8.0 (SD 3.1) at the end of the study. Conclusions: HAE-C1-INH can be significantly improved by one or more injections of C1-INH concentrate per week. However, patients have to accept a large number of intravenous injections and, in some cases, an increase in disease activity.
Multiple Potential Molecular Contributors to Atrial Hypocontractility Caused by Atrial Tachycardia Remodeling in Dogs
Authors: Wakili Reza , Yeh Yung-Hsin , Yan Qi Xiao , Greiser Maura , Chartier Denis , Nishida Kunihiro , Maguy Ange , Villeneuve Louis-Robert , Boknik Peter , Voigt Niels , Krysiak Judith , Kääb Stefan , Ravens Ursula , Linke Wolfgang A. , Stienen Gerrit J.M. , Shi Yanfen , Tardif Jean-Claude , Schotten Ulrich , Dobrev Dobromir , Nattel Stanley
Published: July 2010

Background—

Atrial fibrillation impairs atrial contractility, inducing atrial stunning that promotes thromboembolic stroke. Action potential (AP)-prolonging drugs are reported to normalize atrial hypocontractility caused by atrial tachycardia remodeling (ATR). Here, we addressed the role of AP duration (APD) changes in ATR-induced hypocontractility.

Methods and Results—

ATR (7-day tachypacing) decreased APD (perforated patch recording) by ≈50%, atrial contractility (echocardiography, cardiomyocyte video edge detection), and [Ca
2+
]
i
transients. ATR AP waveforms suppressed [Ca
2+
]
i
transients and cell shortening of control cardiomyocytes; whereas control AP waveforms improved [Ca
2+
]
i
transients and cell shortening in ATR cells. However, ATR cardiomyocytes clamped with the same control AP waveform had ≈60% smaller [Ca
2+
]
i
transients and cell shortening than control cells. We therefore sought additional mechanisms of contractile impairment. Whole-cell voltage clamp revealed reduced I
CaL
; I
CaL
inhibition superimposed on ATR APs further suppressed [Ca
2+
]
i
transients in control cells. Confocal microscopy indicated ATR-impaired propagation of the Ca
2+
release signal to the cell center in association with loss of t-tubular structures. Myofilament function studies in skinned permeabilized cardiomyocytes showed altered Ca
2+
sensitivity and force redevelopment in ATR, possibly due to hypophosphorylation of myosin-binding protein C and myosin light-chain protein 2a (immunoblot). Hypophosphorylation was related to multiple phosphorylation system abnormalities where protein kinase A regulatory subunits were downregulated, whereas autophosphorylation and expression of Ca
2+
-calmodulin-dependent protein kinase IIδ and protein phosphatase 1 activity were enhanced. Recovery of [Ca
2+
]
i
transients and cell shortening occurred in parallel after ATR cessation.

Conclusions—

Shortening of APD contributes to hypocontractility induced by 1-week ATR but accounts for it only partially. Additional contractility-suppressing mechanisms include I
CaL
current reduction, impaired subcellular Ca
2+
signal transmission, and altered myofilament function associated with abnormal myosin and myosin-associated protein phosphorylation. The complex mechanistic basis of the atrial hypocontractility associated with AF argues for upstream therapeutic targeting rather than interventions directed toward specific downstream pathophysiological derangements.
Intracardiac Injection of AdGRK5-NT Reduces Left Ventricular Hypertrophy by Inhibiting NF-κB–Dependent Hypertrophic Gene Expression
Authors: Sorriento Daniela , Santulli Gaetano , Fusco Anna , Anastasio Antonio , Trimarco Bruno , Iaccarino Guido
Published: July 2010

Several studies underline the role of the transcription factor NF-κB in the development of left cardiac hypertrophy (LVH). We have demonstrated recently that the RGS homology domain within the amino terminus of GRK5 (GRK5-NT) is able to inhibit NF-κB transcription activity and its associated phenotypes. The aim of this study was to evaluate the ability of GRK5-NT to regulate LVH through the inhibition of NF-κB both in vitro and in vivo. In cardiomyoblasts, GRK5-NT inhibits phenylephrine-induced transcription of both NF-κB and atrial natriuretic factor promoters, assessed by luciferase assay, thus confirming a role for this protein in the regulation of cardiomyocyte hypertrophy. In vivo, we explored 2 rat models of LVH, the spontaneously hypertensive rat and the normotensive Wistar Kyoto rat exposed to chronic administration of phenylephrine. Intracardiac injection of an adenovirus encoding for GRK5-NT reduces cardiac mass in spontaneously hypertensive rats and prevents the development of phenylephrine-induced LVH in Wistar Kyoto rats. This associates with inhibition of NF-κB signaling (assessed by NF-κB levels), transcriptional activity and phenotypes (fibrosis and apoptosis). Such phenomenon is independent from hemodynamic changes, because adenovirus encoding for GRK5-NT did not reduce blood pressure levels in spontaneously hypertensive rats or in Wistar Kyoto rats. In conclusion, our study supports the regulation of LVH based on the GRK5-NT inhibition of the NF-κB transduction signaling.
Generating Phrasal and Sentential Paraphrases: A Survey of Data-Driven Methods
Authors: Madnani Nitin , Dorr Bonnie J.
Published: July 2010

The task of paraphrasing is inherently familiar to speakers of all languages. Moreover, the task of automatically generating or extracting semantic equivalences for the various units of language—words, phrases, and sentences—is an important part of natural language processing (NLP) and is being increasingly employed to improve the performance of several NLP applications. In this article, we attempt to conduct a comprehensive and application-independent survey of data-driven phrasal and sentential paraphrase generation methods, while also conveying an appreciation for the importance and potential use of paraphrases in the field of NLP research. Recent work done in manual and automatic construction of paraphrase corpora is also examined. We also discuss the strategies used for evaluating paraphrase generation techniques and briefly explore some future trends in paraphrase generation.
Religion and the Crisis of Historicism: Protestant and Catholic Perspectives
Authors: Paul Herman
Published: July 2010

This paper raises the question to what extent the crisis of historicism is to be seen as a religious problem. There is, of course, no need to argue that religion in a broad sense of the word ‐ ultimate concerns and fundamental values ‐ played major roles in the debates over historicism. However, virtually no studies have been conducted on how the crisis of historicism can be “mapped” on the religious landscape in a more specific sense. Which theological schools and which church denominations, for example, were most affected by or concerned over the crisis of historicism? I address this question by presenting three case-studies of Protestant and Roman-Catholic thinkers in the Netherlands. These examples show that especially those Christian intellectuals whose theological or philosophical traditions were indebted to historicist premises participated in debates over historicism. In practical terms, this implies that Protestants of various persuasions were more heavily involved than Roman-Catholics. In a final section, the paper suggests some implications of this finding for how the crisis of historicism is best understood.
Intercity Relations and Globalisation: The Evolution of the Global Urban Hierarchy, 1981—2007
Authors: Alderson Arthur S. , Beckfield Jason , Sprague-Jones Jessica
Published: July 2010

How is the world city system changing in the context of globalisation? This question is addressed using data on the headquarter and branch locations of the world’s 500 largest multinationals. The paper employs techniques developed for the analysis of networks to evaluate the more than 6300 cities that are linked together by such firms in terms of their point centrality and, using blockmodelling techniques, in terms of the positions they occupy and roles that they play in the system. The analysis indicates that the world city system is in the midst of substantial restructuring and that it is changing in such a way as to concentrate power in a small number of cities. However, in contrast to some accounts, support is not found for the idea that globalisation is generating a ‘new geography of inequality’ at the level of intercity relations.
Adolescent Precursors of Early Union Formation Among Asian American and White Young Adults
Authors: Cheng Yen-hsin Alice , Landale Nancy S.
Published: July 2010

Using a framework that emphasizes independent versus interdependent self-construals, this study investigates the relatively low rates of early marriage and cohabitation among Asian Americans compared with Whites. Data from Waves 1 and 3 of Add Health are used to test five hypotheses that focus on family value socialization and other precursors measured in adolescence. Analyses of early marriage indicate that the Asian—White difference is driven primarily by differences in adolescent sexual and romantic relationship experiences and that several measures of family values play a stronger role among Asian Americans than Whites. Asian—White differences in cohabitation persist net of socioeconomic status and other adolescent precursors, but differences are attenuated when parental value socialization, intimate relationship experiences, and educational investments are controlled. These results are interpreted within a culturally sensitive conceptual framework that emphasizes interdependent construals of the self among Asian Americans.
Class Conflict and Industrial Location
Authors: Olsen Erik K.
Published: July 2010

This paper examines the effect of class conflict on industrial location both theoretically and empirically. It demonstrates that there is a sound theoretical basis and empirical support for the conclusion that U.S. industries have chosen to abandon agglomeration and scale economies in order to secure a distribution of income that favors capital at the expense of labor. The decline of the U.S. manufacturing belt is examined with reference to union density, bargaining power, and the effects that large-scale production plants have on these factors. The meat packing industry in the postwar United States serves as a case study to establish the specific ways that class conflict has shaped the scale profile and geographic distribution of production plants. The paper builds upon the class conflict approach to urban and regional economics pioneered by Matthew Edel and David Gordon and aims to demonstrate its explanatory power.

JEL classification: R30, J51, B51.
Distributional Consequences of Financial Crises: Evidence from Recent Crises
Authors: Gezici Armağan
Published: July 2010

The paper examines the distributional consequences of financial crises based on the lessons of the past crises experiences of Argentina, Brazil, Korea, Mexico, and Turkey. It identifies the possible channels through which crises may affect functional and personal distribution of income. It concludes that the crises of the last two decades have both pro-capital and pro-finance distributional outcomes.

JEL classification: D31, E25, O15, G01
Expectancies and Ownership of Long-Term Care Insurance Policies Among Older Married Couples
Authors: Caro Frank G. , Porell Frank W. , Kwan Ngai
Published: July 2010

The study was concerned with perceived risk of need for long-term care (LTC) as a factor in decisions among older married couples to purchase or retain LTC insurance policies. The study examined the relationship between expectancies of moving to a nursing home and ownership of private LTC insurance policies among married couples in which both partners were at least aged 65. Data from the 2002 and 2004 Health and Retirement Study were analyzed. Higher subjective probabilities of moving to a nursing home within the next 5 years among both primary respondents and spouses were positively associated with the primary respondent’s possession of private LTC insurance. The findings add to evidence that among married older people decisions to purchase and retain LTC insurance policies are made jointly. For public education efforts to encourage planning to address LTC financing, the results underscore the importance of attention to the joint concerns of married couples.
Foreign players in the English Premier Academy League: ‘Feet-drain’ or ‘feet-exchange’?
Authors: Elliott Richard , Weedon Gavin
Published: July 2010

The aim of this article is to make sense of the effects of foreign player involvement in English football’s elite youth academy system. Based upon a series of interviews conducted with academy directors, managers, and coaches at Premier League clubs, and senior figures in the Premier League’s Youth Development department, the article argues that the involvement of foreign players should not be viewed negatively where indigenous players are increasingly forced to the margins of the professional game, or where the recruiting of foreign players results in the deskilling of donor nations. By drawing on research located within the area of highly skilled migration, the article argues that the involvement of foreign players can be seen to reflect processes of ‘feet-exchange’ where skills and knowledge circulate to improve overall standards of performance for indigenous and foreign players. The article concludes by arguing that the recruitment of foreign players to English football’s elite youth development system does not appear to act to the detriment of host and donor nations. Rather, by recruiting foreign players to Premier League academies, and by integrating them with indigenous players, a culture is created which enhances the development potential of all players.
A Review of Mathematical and Mechanical Modelling in Nanotechnology
Authors: Thamwattana N. , Hill J.M. , Baowan D. , Cox B.J.
Published: July 2010

Nanotechnology is currently an area of intense research activity. To date there is some limited experimental data, and considerably more computational data arising from molecular dynamics simulations, but there is very little applied mathematical modelling from the disciplines associated with modelling, namely mathematics and mechanics. This paper reviews some of the mathematical and mechanical modelling contributions for interacting molecular structures. Modelling can indicate to the experimentalist materials and geometry where a certain outcome may be anticipated. A combined modelling—computational approach can make efficient a computational procedure that alone is not practical. The present review aims to provide an overview of contributions to date, but is necessarily focussed on the work of the present authors, since the number of mathematically orientated workers in the field is limited.
The physical health challenges in patients with severe mental illness: cardiovascular and metabolic risks
Authors: Deakin Bill , Ferrier Nicol , Holt Richard IG , Millar Helen , Nutt David J , Reynolds Gavin , Samani Nilesh , Taylor David
Published: July 2010

This supplement is the output of a roundtable discussion, attended by a multidisciplinary panel with a broad range of expertise, which includes the treatment of severe mental illness, cardiovascular disease, diabetes and pharmaceutical prescribing.

The roundtable and writing of the supplement were organised and paid for by MSD, including the payment of Steve Titmarsh, a medical writer who was involved in the preparation and editing of this document
Case Control Series of Intrathecal Autologous Bone Marrow Mesenchymal Stem Cell Therapy for Chronic Spinal Cord Injury
Authors: Kishk Nirmeen A. , Gabr Hala , Hamdy Sherif , Afifi Lamia , Abokresha Noha , Mahmoud Hayam , Wafaie Ahmed , Bilal Dalia
Published: July 2010

Background: Autologous bone marrow mesenchymal cells that include stem cells (MSCs) are a clinically attractive cellular therapy option to try to treat severe spinal cord injury (SCI). Objective: To study the possible value of MSCs injected intrathecally to enhance rehabilitation. Methods: This case control, convenience sample included 64 patients, at a mean of 3.6 years after SCI. Forty-four subjects received monthly intrathecal autologous MSCs for 6 months and 20 subjects, who would not agree to the procedures, served as controls. All subjects received rehabilitation therapies 3 times weekly. Subjects were evaluated at entry and at 12 months after completing the 6-months intervention. By the ASIA Impairment Scale, ASIA grading of completeness of injury, Ashworth Spasticity Scale, Functional Ambulation Classification, and bladder and bowel control questionnaire. Results: No differences were found in baseline measures and descriptors between the MSC group and control group. Although a higher percentage of the MSC group increased motor scores by 1-2 points and changed from ASIA A to B, no significant between-group improvements were found in clinical measures. Adverse effects of cells included spasticity and, in 24 out of the 43 patients developed neuropathic pain. One subject with a history of post-infectious myelitis developed encephalomyelitis after her third injection. Conclusion: Autologus MSCs may have side effects and may be contraindicated in patients with a history of myelitis. Their utility in treating chronic traumatic SCI needs further study in pre-clinical models and in randomized controlled trials before they should be offered to patients.
Diagnostic delay and clinical modifiers in alpha-1 antitrypsin deficiency
Authors: Köhnlein Thomas , Janciauskiene Sabina , Welte Tobias
Published: July 2010

Background: Alpha-1 antitrypsin deficiency (AATD) is one of the most prevalent inherited diseases in Whites, but identification of affected patients and establishment of the diagnosis is still unsatisfactory. This study assessed the latencies and numbers of physicians involved in identifying AATD patients, and the importance of smoking, vaccination status, and specific augmentation therapy on the course of the disease.

Method: Patients from Germany and Austria underwent a single written interview with 28 items. Five hundred and ninety-six patients were addressed and 44.9% replied.

Results: The age at symptom onset was 39.1±10.1 years, and the diagnosis was established at the age of 45.1±10.9 years. From the 6-year delay in establishing the diagnosis, 1.4±1.7 (range 0.5—10.5) years were due to patients’ reluctance to seek medical attention. There were 3.2±2.4 (range 1—13) physicians involved in establishing the diagnosis. Smoking was associated with an earlier onset of respiratory symptoms and lower exercise capacity. Vaccination against pneumococci and/or influenza, and augmentation therapy resulted in significantly fewer exacerbations and fewer emergency room visits. Airway infections and passive smoking during childhood were not found to influence the onset of respiratory symptoms.

Conclusions: In conclusion, there is still a large delay between symptom onset and AATD diagnosis. Smoking history, vaccination status, and augmentation therapy have an important impact on the course of the disease.
Darapladib: an emerging therapy for atherosclerosis
Authors: Corson Marshall A.
Published: July 2010

Despite a reduction in cardiovascular risk conferred by therapies that modify circulating lipids, a need remains for novel treatments to further decrease the occurrence of complications of atherosclerotic cardiovascular diseases. Lipoprotein-associated phospholipase-A2 is an important regulator of lipid metabolism and inflammation that circulates with lipoprotein particles and is carried into the arterial wall with low-density lipoprotein particles during the progression of atherosclerosis. Within the vessel wall, lipoprotein-associated phospholipase-A2 releases small molecules that stimulate macrophage recruitment and evolution to foam cells, leading to plaque vulnerability. Epidemiologic studies demonstrate that elevated circulating levels of lipoprotein-associated phospholipase-A2 predict an increased risk of myocardial infarction and stroke, whereas histologic examination of diseased human coronary arteries reveals intense presence of the enzyme in atherosclerotic plaques that are prone to rupture. These considerations suggest lipoprotein-associated phospholipase-A2 as a promising therapeutic target, and a specific inhibitor, darapladib, has been under development for this application. This review summarizes the completed preclinical and early phase clinical studies that underlie two recently commenced phase III clinical trials that will investigate the efficacy and safety of darapladib in nearly 13,000 individuals with coronary heart disease. When completed, these trials should provide important insights into the utility of darapladib to reduce myocardial infarction, stroke and cardiovascular death.
Determinants of participation in colonoscopic screening by siblings of colorectal cancer patients in France
Authors: Taouqi Myriam , Ingrand Isabelle , Beauchant Michel , Migeot Virginie , Ingrand Pierre
Published: July 2010

Background

Targeted colonosocopic screening is recommended for first-degree relatives of colorectal cancer patients diagnosed before the age of 60 and offers the possibility of reducing morbidity and mortality, but participation remains too low. The objective of this study was to determine in a French population the factors that affect siblings' participation in screening, notably those relating to the individuals, their medical care, their family and their social network.

Methods

A cross sectional survey was conducted in siblings of index patients having undergone surgery for colorectal cancer between 1999 and 2002 in two French counties. Siblings were contacted during 2007 and 2008 through the index patient. The factors affecting participation in colonoscopic screening were studied by logistic regression taking into account family cluster effect.

Results

172 siblings of 74 index cases were included. The declared rate of undergoing at least one colonoscopy among siblings was 66%; 95%CI 59-73%. Five variables were independently associated with colonoscopic screening: perceiving fewer barriers to screening (OR = 3.2; 95%CI 1.2-8.5), having received the recommendation to undergo screening from a physician (OR = 4.9; 1.7-13.7), perceiving centres practising colonoscopy as more accessible (OR = 3.2, 1.3-7.8), having discussed screening with all siblings (OR = 3.9; 1.6-9.6) and being a member of an association (OR = 2.6; 1.0-6.6).

Conclusions

The factors independently associated with participation in CRC screening by an individual at increased risk belonged to each of four dimensions relating to his individual psychosocial characteristics, to his relationship with a physician, within the family and social environment. The relevance of these results to clinical practice may help to improve compliance to recommendations in a global preventive strategy including all stages of the information pathway from the physician to the index patient and his relatives.
Protocol for a national audit on self-reported confidence levels, training requirements and current practice among trainee doctors in the UK: The Trainees Own Perception of Delivery of Care in Diabetes (TOPDOC) Study
Authors: George Jyothis T , McGrane David J , Warriner David , Rozario Kavitha S , Price Hermione C , Wilmot Emma G , Kar Partha , Jude Edward B , McKay Gerard A ,   the TOPDOC Study Team
Published: July 2010

Background

As the incidence and prevalence of diabetes increases across the world, resource pressures require doctors without specialist training to provide care for people with diabetes. In the UK, national standards have been set to ensure quality diabetes care from diagnosis to the management of complications. In a multi-centre pilot study, we have demonstrated a lack of confidence among UK trainee doctors in managing diabetes. Suboptimal confidence was identified in a number of areas, including the management of diabetes emergencies. A national survey would clarify whether the results of our pilot study are representative and reproducible.

Methods/Design

Target cohort: All postgraduate trainee doctors in the UK.

Domains Studied: The self reported online survey questionnaire has 5 domains: (1) confidence levels in the diagnosis and management of diabetes, (2) working with diabetes specialists, (3) perceived adequacy of training in diabetes (4) current practice in optimising glycaemic control and (5) perceived barriers to seeking euglycaemia.

Assessment tools: Self-reported confidence is assessed using the 'Confidence Rating' (CR) scale for trainee doctors developed by the Royal College of Physicians. This scale has four points - ('not confident' (CR1), 'satisfactory but lacking confidence' (CR2), 'confident in some cases (CR3) and 'fully confident in most cases' (CR4).

Frequency of aspects of day-to-day practice is assessed using a six-point scale. Respondents have a choice of 'always' (100%), 'almost always' (80-99%), 'often' (50-79%), 'not very often' (20-49%) and 'rarely' (5-19%) or never (less than 5%).

Discussion

It is anticipated that the results of this national study will clarify confidence levels and current practice among trainee doctors in the provision of care for people with diabetes. The responses will inform efforts to enhance postgraduate training in diabetes, potentially improving the quality of care for people with diabetes.
The effect of starting point placement technique on thoracic transverse process strength: an ex vivo biomechanical study
Authors: Brown Barrett S , McIff Terence E , Glattes Rudolph C , Burton Douglas C , Asher Marc A
Published: July 2010

Background

The use of thoracic pedicle screws in spinal deformity, trauma, and tumor reconstruction is becoming more common. Unsuccessful screw placement may require salvage techniques utilizing transverse process hooks. The effect of different starting point placement techniques on the strength of the transverse process has not previously been reported. The purpose of this paper is to determine the biomechanical properties of the thoracic transverse process following various pedicle screw starting point placement techniques.

Methods

Forty-seven fresh-frozen human cadaveric thoracic vertebrae from T2 to T9 were disarticulated and matched by bone mineral density (BMD) and transverse process (TP) cross-sectional area. Specimens were randomized to one of four groups: A, control, and three others based on thoracic pedicle screw placement technique; B, straightforward; C, funnel; and D, in-out-in. Initial cortical bone removal for pedicle screw placement was made using a burr at the location on the transverse process or transverse process-laminar junction as published in the original description of each technique. The transverse process was tested measuring load-to-failure simulating a hook in compression mode. Analysis of covariance and Pearson correlation coefficients were used to examine the data.

Results

Technique was a significant predictor of load-to-failure (P = 0.0007). The least squares mean (LS mean) load-to-failure of group A (control) was 377 N, group B (straightforward) 355 N, group C (funnel) 229 N, and group D (in-out-in) 301 N. Significant differences were noted between groups A and C, A and D, B and C, and C and D. BMD (0.925 g/cm2 [range, 0.624-1.301 g/cm2]) was also a significant predictor of load-to-failure, for all specimens grouped together (P < 0.0001) and for each technique (P < 0.05). Level and side tested were not found to significantly correlate with load-to-failure.

Conclusions

The residual coronal plane compressive strength of the thoracic transverse process is dependent upon the screw starting point placement technique. The funnel technique significantly weakens transverse processes as compared to the straightforward technique, which does not significantly weaken the transverse process. It is also dependent upon bone mineral density, and low failure loads even in some control specimens suggest limited usefulness of the transverse process for axial compression loading in the osteoporotic thoracic spine.
MYBsuppresses differentiation and apoptosis of human breast cancer cells
Authors: Drabsch Yvette , Ramsay Robert G , Gonda Thomas J
Published: July 2010

Introduction

MYB is highly expressed in estrogen receptor positive (ER + ve) breast tumours and tumour cell lines. We recently demonstrated that MYB is essential for the proliferation of ER + ve breast cancer cells, and have now investigated its role in mammary epithelial differentiation.

Methods

MCF-7 breast cancer cells were treated with sodium butyrate, vitamin E succinate or 12-O-tetradecanoylphorbol-13-acetate to induce differentiation as measured by Nile Red staining of lipid droplets and β-casein expression. The non-tumorigenic murine mammary epithelial cell (MEC) line, HC11, was induced to differentiate with lactogenic hormones. MYB levels were manipulated by inducible lentiviral shRNA-mediated knockdown and retroviral overexpression.

Results

We found that MYB expression decreases following chemically-induced differentiation of the human breast cancer cell line MCF-7, and hormonally-induced differentiation of a non-tumorigenic murine mammary epithelial cell (MEC) line, HC11. We also found that shRNA-mediated MYB knockdown initiated differentiation of breast cancer cells, and greatly sensitised them to the differentiative and pro-apoptotic effects of differentiation-inducing agents (DIAs). Sensitisation to the pro-apoptotic effects DIAs is mediated by decreased expression of BCL2, which we show here is a direct MYB target in breast cancer cells. Conversely, enforced expression of MYB resulted in the cells remaining in an undifferentiated state, with concomitant suppression of apoptosis, in the presence of DIAs.

Conclusions

Taken together, these data imply that MYB function is critical in regulating the balance between proliferation, differentiation, and apoptosis in MECs. Moreover, our findings suggest MYB may be a viable therapeutic target in breast cancer and suggest specific approaches for exploiting this possibility.
Efficient, high-throughput transfection of human embryonic stem cells
Authors: Moore Jennifer C , Atze Kristin , Yeung Percy L , Toro-Ramos Alana J , Camarillo Cynthia , Thompson Kevin , Ricupero Christopher L , Brenneman Mark A , Cohen Rick I , Hart Ronald P
Published: July 2010

Introduction

Genetic manipulation of human embryonic stem cells (hESC) has been limited by their general resistance to common methods used to introduce exogenous DNA or RNA. Efficient and high throughput transfection of nucleic acids into hESC would be a valuable experimental tool to manipulate these cells for research and clinical applications.

Methods

We investigated the ability of two commercially available electroporation systems, the Nucleofection® 96-well Shuttle® System from Lonza and the Neon™ Transfection System from Invitrogen to efficiently transfect hESC. Transfection efficiency was measured by flow cytometry for the expression of the green fluorescent protein and the viability of the transfected cells was determined by an ATP catalyzed luciferase reaction. The transfected cells were also analyzed by flow cytometry for common markers of pluripotency.

Results

Both systems are capable of transfecting hESC at high efficiencies with little loss of cell viability. However, the reproducibility and the ease of scaling for high throughput applications led us to perform more comprehensive tests on the Nucleofection® 96-well Shuttle® System. We demonstrate that this method yields a large fraction of transiently transfected cells with minimal loss of cell viability and pluripotency, producing protein expression from plasmid vectors in several different hESC lines. The method scales to a 96-well plate with similar transfection efficiencies at the start and end of the plate. We also investigated the efficiency with which stable transfectants can be generated and recovered under antibiotic selection. Finally, we found that this method is effective in the delivery of short synthetic RNA oligonucleotides (siRNA) into hESC for knockdown of translation activity via RNA interference.

Conclusions

Our results indicate that these electroporation methods provide a reliable, efficient, and high-throughput approach to the genetic manipulation of hESC.