bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolism and Disposition of the Thienopyridine Antiplatelet Drugs Ticlopidine, Clopidogrel, and Prasugrel in Humans
Authors: Farid Nagy A. , Kurihara Atsushi , Wrighton Steven A.
Published: December 2009

Ticlopidine, clopidogrel, and prasugrel are thienopyridine prodrugs that inhibit adenosine‐5′‐diphosphate (ADP)‐mediated platelet aggregation in vivo. These compounds are converted to thiol‐containing active metabolites through a corresponding thiolactone. The 3 compounds differ in their metabolic pathways to their active metabolites in humans. Whereas ticlopidine and clopidogrel are metabolized to their thiolactones in the liver by cytochromes P450, prasugrel proceeds to its thiolactone following hydrolysis by carboxylesterase 2 during absorption, and a portion of prasugrel's active metabolite is also formed by intestinal CYP3A. Both ticlopidine and clopidogrel are subject to major competing metabolic pathways to inactive metabolites. Thus, varying efficiencies in the formation of active metabolites affect observed effects on the onset of action and extent of inhibition of platelet aggregation (IPA). Knowledge of the CYP‐dependent formation of ticlopidine and clopidogrel thiolactones helps explain some of the observed drug‐drug interactions with these molecules and, more important, the role of CYP2C19 genetic polymorphism on the pharmacokinetics of and pharmacodynamic response to clopidogrel. The lack of drug interaction potential and the absence of CYP2C19 genetic effect result in a predictable response to thienopyridine antiplatelet therapy with prasugrel. Current literature shows that greater ADP‐mediated IPA is associated with significantly better clinical outcomes for patients with acute coronary syndrome.
Pharmacokinetics of Once‐Daily Trospium Chloride 60 mg Extended Release and Twice‐Daily Trospium Chloride 20 mg in Healthy Adults
Authors: Silver Nova , Sandage Bobby , Sabounjian LuAnn , Schwiderski Ute , Shipley James , Harnett Mark
Published: December 2009

The objective of this study is to characterize the steady‐state pharmacokinetics and compare the relative bioavailability of the extended‐release capsule formulation of the antimuscarinic trospium chloride, developed for once‐daily administration, and trospium chloride immediate‐release tablets. This is a single‐center, multidose, randomized, open‐label, 2‐period, 2‐arm crossover, bioavailability study in healthy adult male and female subjects who are within 20% of their ideal body weight. Subjects receive trospium 60‐mg extended‐release capsules once daily and trospium 20‐mg tablets twice daily for 10 days, each in a crossover manner. Twenty‐four subjects are enrolled in the study. With multiple dosing of trospium 60 mg extended‐release once daily versus 20 mg twice daily, lower geometric least squares mean area under the concentration—time curve from 0 to 24 hours (17 360 vs 28 590 pg·h/mL; ratio 61%; 90% confidence interval, 51–72) and maximum plasma concentration (1517 vs 2502 pg/mL; 61%; 90% confidence interval, 49–75) are observed. Furthermore, with trospium 60 mg extended‐release versus 20 mg, median time to maximum plasma concentration is later (5.0 vs 4.5 hours) and half‐life is longer (35.8 vs 27.2 hours). Trospium exposure is lower with multiple dosing of trospium 60 mg extended‐release compared with trospium 20 mg twice daily. Thus, with the extended‐release formulation, trospium concentrations are less likely to reach the threshold where adverse events may sometimes occur.
Feminist Identity Attitudes, Negative Affect, and Eating Pathology in African American College Women
Authors: Blue Erika L. , Berkel LaVerne A.
Published: December 2009

African American women are believed to have unique experiences related to eating pathology partially because of the intersection of gender and race in Western society. Investigations of negative affect and identity development as predictors of eating pathology in African American women have yielded mixed results; however, feminist identity development is yet to be examined as a predictor of eating problems in this group. Therefore, the current study investigated feminist identity attitudes, anxiety, and depression as predictors of eating pathology in 98 African American college women. Interestingly, most of the participants endorsed a “Synthesis” feminist identity style. However, negative affect emerged as the only significant predictor of eating pathology. These findings are congruent with previous research that supports significant relations between anxiety, depression, and eating disturbance in women.
Wage and Hour Law in California
Authors: Kilgour John G.
Published: December 2009

Federal and state wage and hour laws are complex and violations can be costly. California law shares some similarities with federal law but also contains some important difference. Generally, California has a highly developed body of wage and hour law that usually exceeds federal requirements. If an employer is in compliance with California law, the federal requirements are also met, with occasional exceptions. Employee exemptions and child labor restrictions are especially hazardous areas. Employers must be vigilant about their compliance practices and maintain training programs for key personnel, including frontline supervisors.
Introduction: Institutional Change and Labour Market Segmentation in European Call Centres
Authors: Doellgast Virginia , Batt Rosemary , Sørensen Ole H.
Published: December 2009

This article examines the dynamics of workplace change in European call centres. Survey data and case studies from Austria, Denmark, France, Germany, the Netherlands and Spain show large national and sectoral differences in institutional inclusiveness and labour market segmentation. These reflect variation in the institutional constraints and resources available to employers and unions as they adjust to market changes. However, union strategies to organize new groups and close gaps in existing regulations are becoming increasingly important as restructuring undermines traditional forms of bargaining power.
Institutional Change and the Restructuring of Service Work in the French and German Telecommunications Industries
Authors: Doellgast Virginia , Nohara Hiroatsu , Tchobanian Robert
Published: December 2009

This study analyses recent changes in collective bargaining institutions and their implications for employer strategies in the French and German telecommunications industries, drawing on case studies and survey data from call centre workplaces. Findings demonstrate that differences in both formal institutions and past logics of action influenced actor responses to changing markets and ownership structures. French trade unions were more successful in establishing encompassing bargaining structures and reducing pressures for pay differentiation, due to state support for the mandatory extension of agreements and unions’ strategic focus on centralizing bargaining. In contrast, bargaining in Germany has become increasingly fragmented and decentralized as unions and works councils focused on company-level bargaining at major employers. This focus allowed worker representatives to preserve their strong influence over employment practices in core workplaces but has contributed to declining bargaining coverage and growing wage inequality.
Pay and Working Conditions in Finance and Utility Call Centres in Denmark and Germany
Authors: Sørensen Ole Henning , Weinkopf Claudia
Published: December 2009

This study analyses how national institutions, sectoral bargaining structures and union strategies affect working conditions and pay by comparing call centres in two liberalized service sectors: financial services and utilities. We find more segmentation and expansion of low wage work in Germany and more cooperation on high-involvement practices at workplace level in Denmark. However, outcomes are not uniform; we find differences between sectors in the use of subcontracting and union power at the workplace-level. Poor economic performance, segmentation-oriented employer strategies, declining bargaining coverage and weakened unions in Germany have undermined formal constraints on employers, whereas better outcomes in Denmark are due to a pronounced stability of the regulative and normative institutional framework. However, the Danish model is also being weakened from the margins.
Collective Bargaining and Temporary Contracts in Call Centre Employment in Austria, Germany and Spain
Authors: Shire Karen A. , Schönauer Annika , Valverde Mireia , Mottweiler Hannelore
Published: December 2009

This study compares the effectiveness of bargaining institutions in regulating temporary contracts in Austrian, German and Spanish call centres. Unions’ capacities to bargain over the expansion and conditions of temporary contract use are shaped by bargaining structures and state regulation of various temporary contract types. National capacities to regulate the use of outsourcing and coordinate collective agreements with workplace bargaining are particularly effective in limiting the use of temporary contracts. Nonetheless, cross-national analysis indicates that employers are adept at exploiting very specific forms of temporary contracts in order to circumvent regulations and evade collective bargaining.
Study of p53 codon 72 polymorphism and codon 249 mutations in Southern India in relation to age, alcohol drinking and smoking habits
Authors: Pandima Devi K. , Sivamaruthi B. , Kiruthiga PV , Karutha Pandian S.
Published: December 2009

Germline polymorphisms of genes involved in different steps of tumorigenesis like p53, the tumor suppressor gene, are reported to determine the individual susceptibility to cancer. Lung cancer is one of the most common and lethal cancers and tobacco smoking remains its most important etiologic factors. The most frequently p53 mutated codons of lung cancer are 72 (exon 4) and 249 (exon 7). Since mutations in the p53 gene are present in ∼40% of all human lung cancers and are more common in smokers than in nonsmokers, we aimed to detect the status of p53 at codon 72 for Arg/Arg or Arg/Pro or Pro/Pro allele polymorphism and p53 codon 249 mutation in smokers and nonsmokers of South India. Allele frequencies in the nonsmokers were 0.16 for the Arg/Pro allele and 0.84 for the Pro/Pro allele in our study population. Among the smokers, the frequencies of the Arg/Pro, Arg/Arg, and Pro/Pro alleles were 0.88, 0.04, and 0.08, respectively. No mutation was detected in both smokers and nonsmokers in p53 codon 249. From the worldwide scenario, it can be speculated that the smokers, with Arg/Pro genotype are more prone for lung cancer or to other types of cancer.
Accepting Being Poz: The Incorporation of the HIV Identity Into the Self
Authors: Baumgartner Lisa M. , David Keegan N.
Published: December 2009

In a previous study, the first author of the current study examined how people who were diagnosed with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) when it was considered a terminal illness incorporated their HIV/AIDS identity into the self over time. In the qualitative study reported here, we examined HIV identity incorporation in participants diagnosed with HIV after 1996, when it was considered a chronic illness in the United States. We uncovered a three-step process: diagnosis, a postdiagnosis turning point, and integration. We compared and contrasted the results to those from the previous study and studies of other chronic illnesses. The findings advance our understanding of HIV/AIDS, chronic illness, and identity. Practical implications for HIV/AIDS educators are also discussed.
Disclosure Outcomes, Coping Strategies, and Life Changes Among Women Living With HIV in Uganda
Authors: Medley Amy M. , Kennedy Caitlin E. , Lunyolo Stella , Sweat Michael D.
Published: December 2009

An HIV diagnosis is a life-changing event. Disclosure of HIV test results might be related to developing effective coping strategies. We conducted qualitative, in-depth interviews with 30 HIV-infected women in Uganda to explore links between HIV disclosure and coping strategies. Many women experienced an evolution in their ability to cope from initial shame to eventual acceptance. Factors that facilitated adaptive coping included being healthy, feeling responsible for children, support group participation, forming supportive relationships, and low perceived stigma and discrimination. HIV disclosure was often the first step in this coping process. Overall, 80% of the women had disclosed, with most reporting positive outcomes. Development of adaptive coping strategies and HIV serostatus disclosure are closely related, as they allow women to develop support networks and begin coming to terms with their diagnosis. Strategies are needed to safely support women who want to disclose their HIV test results.
Struggling to Survive: The Difficult Reality of Aboriginal Women Living With HIV/AIDS
Authors: McCall Jane , Browne Annette J. , Reimer-Kirkham Sheryl
Published: December 2009

The increasingly high rates of mortality and morbidity among Canadian Aboriginal women who are living with HIV/ AIDS indicate that there is a need to address deficiencies in the delivery of supportive services and health care. The purpose of this qualitative study was to develop a greater understanding of the barriers, challenges, and successes experienced when accessing health and related support services from the perspective of Aboriginal women living with HIV/AIDS. The findings are organized around four themes reflected in the interview data: fear of rejection when seeking services, finding strength in adversity, struggles with symptoms, and HIV as just one of many competing problems. It is anticipated that the findings from the study will be used to inform decision making regarding the development and delivery of appropriate, responsive, and accessible policies and programs that will support Aboriginal women who are living with HIV/AIDS.
Beliefs About Participation-Based Practices in Early Intervention
Authors: Sawyer L. Brook E. , Campbell Philippa H.
Published: December 2009

Researchers have noted divergent findings with respect to the relationships of practitioners’ beliefs and their implementation of recommended practices. With Q-sort methods, this study examined practitioners’ beliefs about practices in early intervention with samples of current practitioners ( n = 211) and preservice students ( n = 142). Findings indicated that practitioners rated participation-based practices as less strongly held beliefs when compared with several other early intervention practices, and students’ responses revealed beliefs that were in contrast with participation-based beliefs. In addition, results showed that practitioners’ beliefs were more similar to respondents from institutions of higher education than were the preservice students.
L’arte D’arrangiarsi: Evaluation of an Innovative Practice in a Preservice Practicum
Authors: Macy Marisa , Squires Jane
Published: December 2009

Building on Opportunities for Student Teaching and Learning (BOOST) is a community-based summer preschool program developed, implemented, and coordinated by student teachers, university supervisors, and faculty. Ten preservice graduate students participated in BOOST practicum activities during the spring and summer terms of their 1-year Early Intervention/ Early Childhood Special Education (EI/ECSE) master’s degree program. Eleven children with and without developmental delays attended the preschool program during the 5-week summer term. The student teachers, supervisors/faculty, and families evaluated the effectiveness of the BOOST practicum. Results have implications for alternatives to traditional student teaching and practicum experiences.
Gender and Circadian Effects of Myocardial Infarctions
Authors: Matura Lea Ann
Published: December 2009

This study determines if there are differences in circadian effects of myocardial infarctions (MIs) and MI type, non-ST elevation MI (NSTEMI) and ST elevation MI (STEMI), between females and males. A two-group, nonexperimental chart review was conducted. A total of 273 randomly selected patients with an acute MI were included. Data analysis included descriptive statistics, t test and chi square to determine differences between the groups. Of the 109 females, 26% had MI symptoms begin at night, 30% in the morning, 29% in the afternoon, and 15% in the evening ( p = .067). In comparison, of the 164 males, 27% had MIs at night, 30% morning, 32% afternoon, and 11% evening ( p < .001). There was no circadian difference between females and males and the time of day MI-related symptoms began ( p = .887) or a MItype circadian effect ( p = 0.466). The majority of patients had MIs during the daytime hours.
Does the Inclusion Criterion of Women’s Aggression as Opposed to Their Victimization Result in Samples That Differ on Key Dimensions of Intimate Partner Violence?
Authors: Sullivan Tami P. , Titus Jennifer A. , Holt Laura J. , Swan Suzanne C. , Fisher Bonnie S. , Snow David L.
Published: December 2009

This study is among the first attempts to address a frequently articulated, yet unsubstantiated claim that sample inclusion criteria based on women’s physical aggression or victimization will yield different distributions of severity and type of partner violence and injury. Independent samples of African American women participated in separate studies based on either inclusion criterion of women’s physical aggression or victimization. Between-groups comparisons showed that samples did not differ in physical, sexual, or psychological aggression; physical, sexual, or psychological victimization; inflicted or sustained injury. Therefore, inclusion criterion based on physical aggression or victimization did not yield unique samples of “aggressors” and “victims.”
Review Essay: The Elephants in the Room: Ethnicity and Violence Against Women in Post-Communist Slovakia
Authors: Wasileski Gabriela , Miller Susan L.
Published: December 2009

This essay examines the complexities in understanding the issues related to intimate partner violence in Slovakia. It explores the cultural factors as well as the EU efforts that influence the quest to implement measures designed to document, eliminate, and prevent violence against women in pre- and post-Communist Slovakia. In addition, this article addresses the general toleration of domestic violence, particularly when it occurs within the Roma ethnic group, and the attitudes of government entities, public authorities, and nonprofit organizations in their reform efforts. This article concludes with some suggestions for future research and policy.
Why Religion’s Burdens Are Light: From Religiosity to Implicit Self-Regulation
Authors: Koole Sander L. , McCullough Michael E. , Kuhl Julius , Roelofsma Peter H. M. P.
Published: December 2009

To maintain religious standards, individuals must frequently endure aversive or forsake pleasurable experiences. Yet religious individuals on average display higher levels of emotional well-being compared to nonreligious individuals. The present article seeks to resolve this paradox by suggesting that many forms of religion may facilitate a self-regulatory mode that is flexible, efficient, and largely unconscious. In this implicit mode of self-regulation, religious individuals may be able to strive for high standards and simultaneously maintain high emotional well-being. A review of the empirical literature confirmed that religious stimuli and practices foster implicit self-regulation, particularly among individuals who fully internalized their religion’s standards. The present work suggests that some seemingly irrational aspects of religion may have important psychological benefits by promoting implicit self-regulation.
Size Does Matter: How Varying Group Sizes in a Sample Affect the Most Common Measures of Group Diversity
Authors: Biemann Torsten , Kearney Eric
Published: December 2009

Work group diversity can be conceptualized in different ways (i.e., variety, separation, and disparity), and the appropriate operationalization of a diversity dimension depends on which of these diversity types researchers have in mind. Based on prior work on the measurement of the different types of diversity, we show that the most common diversity indexes (i.e., Blau’s index, Teachman’s index, standard deviation, mean Euclidean distance [MED], Gini coefficient, and coefficient of variation) are systematically biased whenever they are used in field studies in which the overall sample comprises groups of varying sizes. Using simulated data, we illustrate this bias inherent in all of the common diversity measures. This bias can lead to erroneous conclusions concerning the impact of group size and the relationship between group diversity and group outcomes. We offer bias-corrected formulas and suggest that diversity researchers henceforth use these adjusted versions when investigating the effects of group diversity in organizational settings.
Method Variance From the Perspectives of Reviewers: Poorly Understood Problem or Overemphasized Complaint?
Authors: Pace Victoria L.
Published: December 2009

Beliefs and practices regarding common method variance (CMV) were surveyed from a sample of top journal board members. Results indicated that reviewers frequently mentioned CMV concerns and believed that addressing this issue in the design stage was more effective than postdata approaches. Although there was little consensus regarding whether concerns about CMV would cause them to recommend rejection of manuscripts, reviewers generally agreed that some variables were more likely than others to be affected by CMV and that a simple focus on the method of measurement was not adequate for determining whether CMV caused problems with the interpretation of study results. Slight differences were observed across journals and were related to participant experience.
Underlying mechanisms linking music education and cognitive modifiability
Authors: Portowitz Adena , Lichtenstein Osnat , Egorova Ludmula , Brand Eva
Published: December 2009

This study evaluated the impact of a music program designed to foster cognitive development and social esteem among high-risk elementary school children. Addressing the central question of how music education may help children develop general learning skills, the research design interconnected between three components: (1) the content of the music lessons; (2) interactive, educational frameworks (mediated learning environments); and (3) specific learning skills to be fostered during the music lessons. All of the participants ( N = 81) attended the Jaffa Institute Child-Care Centers. Children in the experimental group ( n = 45) partook in two to three hours a week of music enrichment (music appreciation, performance, creativity) conducted within mediated learning environments over a period of 2 years, while children in the control group ( n = 36) did not. Pre and post assessments evaluated the development of cognitive skills (Raven, Complex Figure Tests) and social esteem (Fitts). Results indicated significant differences between the groups in the development of the targeted cognitive skills.
Boys’ descriptions of their experiences in choral music
Authors: Freer Patrick K.
Published: December 2009

This article centers on the accounts of six boys of their experiences in school choral music. The narrative excerpts are drawn from the stories of boys enrolled at a private school in the southeastern USA. The study sampled three categories of boys: those who have sung continuously, those who sang but later withdrew from choral music, and those who did not sing at all. Analysis of the boys’ broad narratives revealed allusions to components of optimal ‘flow’ experiences identified by Csikszentmihalyi and others. Such ‘flow’ experiences are characterized by high levels of both perceived challenge and perceived skill, a clarity of goals, deep personal involvement and concentration, self-directedness, self-awareness, the receiving of immediate feedback and a lack of awareness concerning time constraints. The report concludes with implications for choral music educators who seek to design pedagogy and rehearsal techniques that enable the emergence of these optimal experiences.
Elderly people with multi-morbidity and acute coronary syndrome: Doctors’ views on decision-making
Authors: Ekerstad Niklas , Löfmark Rurik , Carlsson Per
Published: December 2009

Background: In most Western countries the growing gap between available resources and greater potential for medical treatment has brought evidence-based guidelines into focus. However, problems exist in areas where the evidence base is weak, e.g. elderly patients with heart disease and multiple co-morbidities. Objective: Our aim is to evaluate the views of Swedish cardiologists on decision-making for elderly people with multiple co-morbidities and acute coronary syndrome without ST-elevation (NSTE ACS), and to generate some hypotheses for testing. Methods: A confidential questionnaire study was conducted to assess the views of cardiologists/internists (n = 370). The response rate was 69%. Responses were analyzed with frequencies and descriptive statistics. When appropriate, differences in proportions were assessed by a chi-square test. A content analysis was used to process the answers to the open-ended questions. Results: 81% of the respondents reported extensive use of national guidelines for care of heart disease in their clinical decision-making. However, when making decisions for multiple-diseased elderly patients, the individual physician’s own clinical experience and the patient’s views on treatment choice were used to an evidently greater extent than national guidelines. Approximately 50% estimated that they treated multiple-diseased elderly patients with NSTE ACS every day. Preferred measures for improving decision-making were: (a) carrying out treatment studies including elderly patients with multiple co-morbidities, and (b) preparing specific national guidelines for multiple-diseased elderly patients. Conclusions: In the future, national guidelines for heart disease should be adapted in order to be applicable for elderly patients with multiple co-morbidities.
Sexual behaviour and risk assessment in different age cohorts in the general population of Sweden (1989—2007)
Authors: Herlitz Claes A. , Forsberg Margareta
Published: December 2009

Aim: The aim of this investigation was to study the development of sexual attitudes, behaviour and risk assessment in adolescents and young adults, 16—24 years, compared with older adults, 25—44 years, between 1989 and 2007. Methods: We conducted mailed questionnaire surveys in random samples of the Swedish general population in 1989, 1994, 1997, 2000, 2003, and 2007 (total n = 16,773). Each sample consisted of 4,000—6,000 participants, stratified by age. The overall participation rate for men was 54% and for women was 70%. Results: The likelihood of holding a restrained attitude to sexual intercourse outside of a stable relationship decreased significantly throughout the period of study, particularly for the 16—24 year olds. The odds ratio for more than two sexual partners and casual sexual intercourse without using a condom during the preceding 12 months increased significantly in the younger age group, particularly for young women. For women aged 16—24 years, the prevalence of several sexual partners and casual sexual intercourse without the use of a condom doubled between 1989 and 2007. In 2007 there was no difference in this respect between young men and young women. There were small changes in risk assessment associated with HIV infection during the study period. Conclusions: Sexual risk behaviour increased signficantly for 16—24 year olds, and particularly young women, during the study period. To reduce the risk of uncontrollable spread of sexually transmitted infections in this age group, it is imperative that condom use in risky sexual contact is encouraged.
Childe, Marxism, and Knowledge
Authors: Gathercole Peter
Published: December 2009

Childe withdrew from revolutionary politics after his post-university years in Australia in favour of a career in prehistoric archaeology in Britain. Though remaining a Marxist, his application of Marxist principles to prehistory developed only slowly as his interpretations became more sophisticated. He became increasingly interested in knowledge about prehistory from studying results of the interactions between material remains and their interpretation (in Marxist terms, the relationships between practice and theory). In his paper ‘Retrospect’, Childe (1958b:73) charted the development in his thinking to where he rejected ‘transcendental laws determining history and mechanical causes … automatically shaping its course’ with an understanding that a prehistoric society's knowledge of itself was ‘known or knowable … with its then existing material and conceptual equipment’. Thus the prehistory of Europe could be seen not as a product of Oriental civilization, but as an independent entity. Childe could then write a prehistory of Europe ‘that should be both historical and scientific’ (1958b:74). This book,The Prehistory of European Society(1958a), also demonstrated his use of the epistemology of knowledge to understand prehistory as a sociological phenomenon.
A Childe Bibliography: A Hand-List of the Works of Vere Gordon Childe
Authors: Gathercole Peter , Irving Terry , Díaz-Andreu Margarita
Published: December 2009

This hand-list is devoted to the published writings of Vere Gordon Childe (1892–1957). It was compiled for two reasons: the limitations of earlier lists of his works, and the changing needs of scholars studying Childe and the disciplines to which he contributed.

The earliest and then most complete list of Childe’s writings was produced by Isobel Smith for the Childe festschrift published in the Proceedings of the Prehistoric Society 21(1956): 295–304. Both Bruce Trigger and Sally Green have added items missed by Smith to the bibliographies of their books on Childe. However, the present bibliography contains over twice as many published items by Childe as have appeared previously.
‘A new Professor of a Somewhat Obscure Subject’: V. Gordon Childe at the London Institute of Archaeology, 1946–1956
Authors: Harris David R.
Published: December 2009

The context of Childe's decade as Director of the Institute of Archaeology and Professor of Prehistoric European Archaeology in the University of London is described. Particular attention is given to the circumstances leading to his appointment; his participation in a conference on ‘The Future of Archaeology’ held at the Institute in 1943; his inaugural lecture, ‘Archaeology as a Social Science’, delivered in 1946; his and Frederick Zeuner's involvement in the beginnings of radiocarbon dating; and his contrasted contributions as administrator, excavator, and teacher during his 10 years at the Institute.
Late Antiquity by Gordon Childe: Sources and Inspirations
Authors: Jastrzębowska Elżbieta
Published: December 2009

In the last chapter ofWhat Happened in History, Childe touched on the problematic of Late Antiquity. His pessimistic view of that period was a variation on the theme of decadence. This theme had existed in the Roman Republic and under the Empire, long before there was any Late Antiquity to be decadent. It then persisted throughout the Middle Ages and found monumental expression in Gibbon'sDecline and Fall. Childe, however, took it to excessive lengths in his denunciation of the politics, economy, and culture of the Late Roman Empire. Childe based his arguments largely on the work of Rostovtzeff and Heichelheim. Both these eminent historians were exiles: Rostovtzeff from the Russia of the October Revolution and Heichelheim from National Socialist Germany. It is no belittlement to say that their work was influenced by the insights of their political experiences. Childe, however, did not appreciate this and adopted their thinking somewhat uncritically. He further added parallels between the Roman Period and his own time, which resulted in an unduly dark vision of the last phase of the Roman Empire.
The Young Gordon Childe and Transylvanian Archaeology: The Archaeological Correspondence Between Childe and Ferenc László
Authors: László Attila
Published: December 2009

This article presents six original letters from V. Gordon Childe and the draft replies by the archaeologist Ferenc László, written between 1923 and 1925. László worked at the Szekler (Székely) National Museum of Sf. Gheorghe and was known for his methodical excavations of the late Neolithic (Chalcolithic) painted pottery settlement of Ariuşd (Erősd). The correspondence provides new data on Childe's interest in the archaeology of Transylvania, especially as regards the existence in the area of prehistoric cultures with painted pottery, on which limited published information was available to him. In this article it will be shown that correspondence was one of the main methods Childe used to gather documentation for his book The Dawn of European Civilization.
British Asian Girls, Crime and Youth Justice
Authors: Toor Sunita
Published: December 2009

This article provides an understanding of the role of honour ( izzat) and shame ( sharam) in the lives of British Asian girls. It indicates key facets embedded in izzat and sharam that determine and shape the experience of punishment for Asian criminal girls in Britain. In addition, the article provides an insight into why, as a consequence of izzat and sharam, Asian girls are especially invisible as offenders in the youth justice system. Finally, an understanding of izzat and sharam highlights the limitations of using restorative justice practices with Asian young offenders.
Narrative and the Re/production of Transsexual: The Foreclosure of an Endured Emergence of Gender Multiplicity
Authors: Kaufmann Jodi
Published: December 2009

In some autobiographical narratives, transsexual has been narrated outside the gender binary. These narratives have the propensity to reconceptualize multiplicity of genders. However, the re/production of transsexual appears not only to be a function of how the subject position is represented but also a function of the structure of narrative. If this is so, then the following questions arise: What is the relation between the representation of a subject position in a narrative and the structure of narrative? and how does this relation function in the re/production of transsexual and gender multiplicity? In an analysis of one autobiographical interview, the author reads male-to-female transsexual as a subject position grounded in dichotomous gender that was disrupted only where ambiguity is allowed in the narrative structure, and this disruption was foreclosed through how the subject was represented and/or the structure of the narrative.
Safety and Tolerability of Donepezil in Mild Cognitive Impairment: Open-Label Extension Study
Authors: Doody Rachelle S. , Ferris Steven , Salloway Stephen , Yijun Sun  , Goldman Robert , Yikang Xu  , Gao Jeff , Murthy Anita K.
Published: December 2009

Following a 48-week, double-blind, randomized, placebo-controlled trial of donepezil in 821 patients with amnestic mild cognitive impairment (aMCI), safety and tolerability of donepezil (10 mg) were further evaluated in a 28-week extension study. Of 499 participants who completed the double-blind phase, 145 enrolled in the open-label study. Adverse events (AEs) were recorded throughout. Overall, 57.4% of participants in the donepezil/donepezil group and 62.3% in the placebo/donepezil group experienced an AE, with the most frequent treatment-emergent AEs being diarrhea, muscle spasms, insomnia, and nausea. Most were mild to moderate in severity and were more common in the first several weeks after treatment initiation. More participants in the placebo/donepezil group (22.1%) discontinued donepezil due to an AE compared with the donepezil/donepezil group (10.3%). These findings support the safety of donepezil in patients with aMCI. When compared with other studies, however, the data suggest that patients with Alzheimer’s tolerate donepezil better than patients with MCI.
Medical Marijuana in HIV-Positive Patients: What Do We Know?
Authors: Cinti Sandro
Published: December 2009

On November 4, 2008, our state passed the Michigan Medical Marijuana Act (MMMA), which allows the medical use of marijuana for certain conditions and/or constellation of symptoms. This article will (1) review the current evidence that medical marijuana is useful for certain chronic conditions, particularly pain and wasting syndromes experienced by HIV-positive people; (2) discuss the adverse effects of marijuana; (3) summarize the new Michigan law and the challenges it poses for physicians, and (4) review the experience in California where medical marijuana has been legal since 1996.
Patient Readiness to Adhere to HAART
Authors: Grimes Richard M. , Grimes Deanna E.
Published: December 2009

Objectives: to determine 1) whether patients’ statements of readiness to take HAART predicted adherence and 2) whether previous experience with HAART enabled patients to better predict adherence. Method: Thirty-nine patients (24 naïve to HAART and 15 reinitiating HAART after a hiatus of >6 months) indicated readiness to take HAART on a Likert scale and a visual analog scale (VAS). Adherence was measured by prescription renewals. Results: Participants were 72% male; 62% African/American; 23% Anglo-White, and 13% Hispanic. Patients considered themselves quite ready to initiate therapy on both scales. Adherence for 5 months ranged from 24% to 100%; mean = 68%; median = 78%. Adherence was not associated with readiness as measured by the Likert scale (F = .15, p = .86) or the VAS (r = -.078, p = .64). VAS readiness scores did not correlate with adherence for naïve (r = -.16; p = .47) or experienced (r = .09; p = .76) patients. Conclusions: Patients’ statements of readiness to take HAART do not predict their adherence.
Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type
Authors: Huang Yenlin , de Reyniès Aurélien , de Leval Laurence , Ghazi Bouchra , Martin-Garcia Nadine , Travert Marion , Bosq Jacques , Brière Josette , Petit Barbara , Thomas Emilie , Coppo Paul , Marafioti Teresa , Emile Jean-François , Delfau-Larue Marie-Hélène , Schmitt Christian , Gaulard Philippe
Published: December 2009

Biopsies and cell lines of natural killer/T-cell lymphoma, nasal type (NKTCL) were subject to combined gene expression profiling and array-based comparative genomic hybridization analyses. Compared with peripheral T-cell lymphoma, not otherwise specified, NKTCL had greater transcript levels for NK-cell and cytotoxic molecules, especially granzyme H. Compared with normal NKcells, tumors were closer to activated than resting cells and overexpressed several genes related to vascular biology, Epstein-Barr Virus–induced genes, and PDGFRA. Notably, platelet-derived growth factor receptor α and its phosphorylated form were confirmed at the protein level, and in vitro the MEC04 NKTCL cell line was sensitive to imatinib. Deregulation of the AKT, Janus kinase–signal transducers and activators of transcription, and nuclear factor-κB pathways was corroborated by nuclear expression of phosphorylated AKT, signal transducers and activators of transcription 3, and RelA in NKTCL, and several deregulated genes in these pathways mapped to regions of recurrent copy number aberrations (AKT3 [1q44], IL6R [1q21.3], CCL2 [17q12], TNFRSF21 [6p12.3]). Several features of NKTCL uncovered by this analysis suggest perturbation of angiogenic pathways. Integrative analysis also evidenced deregulation of the tumor suppressor HACE1 in the frequently deleted 6q21 region. This study highlights emerging oncogenic pathways in NKTCL and identifies novel diagnostic and therapeutic targets.
Prion protein self-peptides modulate prion interactions and conversion
Authors: Rigter Alan , Priem Jan , Timmers-Parohi Drophatie , Langeveld Jan PM , van Zijderveld Fred G , Bossers Alex
Published: December 2009

Background

Molecular mechanisms underlying prion agent replication, converting host-encoded cellular prion protein (PrPC) into the scrapie associated isoform (PrPSc), are poorly understood. Selective self-interaction between PrP molecules forms a basis underlying the observed differences of the PrPC into PrPSc conversion process (agent replication). The importance of previously peptide-scanning mapped ovine PrP self-interaction domains on this conversion was investigated by studying the ability of six of these ovine PrP based peptides to modulate two processes; PrP self-interaction and conversion.

Results

Three peptides (octarepeat, binding domain 2 -and C-terminal) were capable of inhibiting self-interaction of PrP in a solid-phase PrP peptide array. Three peptides (N-terminal, binding domain 2, and amyloidogenic motif) modulated prion conversion when added before or after initiation of the prion protein misfolding cyclic amplification (PMCA) reaction using brain homogenates. The C-terminal peptides (core region and C-terminal) only affected conversion (increased PrPres formation) when added before mixing PrPC and PrPSc, whereas the octarepeat peptide only affected conversion when added after this mixing.

Conclusion

This study identified the putative PrP core binding domain that facilitates the PrPC-PrPSc interaction (not conversion), corroborating evidence that the region of PrP containing this domain is important in the species-barrier and/or scrapie susceptibility. The octarepeats can be involved in PrPC-PrPSc stabilization, whereas the N-terminal glycosaminoglycan binding motif and the amyloidogenic motif indirectly affected conversion. Binding domain 2 and the C-terminal domain are directly implicated in PrPC self-interaction during the conversion process and may prove to be prime targets in new therapeutic strategy development, potentially retaining PrPC function. These results emphasize the importance of probable PrPC-PrPC and required PrPC-PrPSc interactions during PrP conversion. All interactions are probably part of the complex process in which polymorphisms and species barriers affect TSE transmission and susceptibility.
Derivation of an amino acid similarity matrix for peptide:MHC binding and its application as a Bayesian prior
Authors: Kim Yohan , Sidney John , Pinilla Clemencia , Sette Alessandro , Peters Bjoern
Published: December 2009

Background

Experts in peptide:MHC binding studies are often able to estimate the impact of a single residue substitution based on a heuristic understanding of amino acid similarity in an experimental context. Our aim is to quantify this measure of similarity to improve peptide:MHC binding prediction methods. This should help compensate for holes and bias in the sequence space coverage of existing peptide binding datasets.

Results

Here, a novel amino acid similarity matrix (PMBEC) is directly derived from the binding affinity data of combinatorial peptide mixtures. Like BLOSUM62, this matrix captures well-known physicochemical properties of amino acid residues. However, PMBEC differs markedly from existing matrices in cases where residue substitution involves a reversal of electrostatic charge. To demonstrate its usefulness, we have developed a new peptide:MHC class I binding prediction method, using the matrix as a Bayesian prior. We show that the new method can compensate for missing information on specific residues in the training data. We also carried out a large-scale benchmark, and its results indicate that prediction performance of the new method is comparable to that of the best neural network based approaches for peptide:MHC class I binding.

Conclusion

A novel amino acid similarity matrix has been derived for peptide:MHC binding interactions. One prominent feature of the matrix is that it disfavors substitution of residues with opposite charges. Given that the matrix was derived from experimentally determined peptide:MHC binding affinity measurements, this feature is likely shared by all peptide:protein interactions. In addition, we have demonstrated the usefulness of the matrix as a Bayesian prior in an improved scoring-matrix based peptide:MHC class I prediction method. A software implementation of the method is available at: http://www.mhc-pathway.net/smmpmbec.
Aberrant trafficking of NSCLC-associated EGFR mutants through the endocytic recycling pathway promotes interaction with Src@
Authors: Chung Byung Min , Raja Srikumar M , Clubb Robert J , Tu Chun , George Manju , Band Vimla , Band Hamid
Published: December 2009

Background

Epidermal growth factor receptor (EGFR) controls a wide range of cellular processes, and altered EGFR signaling contributes to human cancer. EGFR kinase domain mutants found in non-small cell lung cancer (NSCLC) are constitutively active, a trait critical for cell transformation through activation of downstream pathways. Endocytic trafficking of EGFR is a major regulatory mechanism as ligand-induced lysosomal degradation results in termination of signaling. While numerous studies have examined mutant EGFR signaling, the endocytic traffic of mutant EGFR within the NSCLC milieu remains less clear.

Results

This study shows that mutant EGFRs in NSCLC cell lines are constitutively endocytosed as shown by their colocalization with the early/recycling endosomal marker transferrin and the late endosomal/lysosomal marker LAMP1. Notably, mutant EGFRs, but not the wild-type EGFR, show a perinuclear accumulation and colocalization with recycling endosomal markers such as Rab11 and EHD1 upon treatment of cells with endocytic recycling inhibitor monensin, suggesting that mutant EGFRs preferentially traffic through the endocytic recycling compartments. Importantly, monensin treatment enhanced the mutant EGFR association and colocalization with Src, indicating that aberrant transit through the endocytic recycling compartment promotes mutant EGFR-Src association.

Conclusion

The findings presented in this study show that mutant EGFRs undergo aberrant traffic into the endocytic recycling compartment which allows mutant EGFRs to engage in a preferential interaction with Src, a critical partner for EGFR-mediated oncogenesis.
A modifier screen in the Drosophila eye reveals that aPKC interacts with Glued during central synapse formation
Authors: Ma Lisha , Johns Louise A , Allen Marcus J
Published: December 2009

Background

The Glued gene of Drosophila melanogaster encodes the homologue of the vertebrate p150Glued subunit of dynactin. The Glued
1 mutation compromises the dynein-dynactin retrograde motor complex and causes disruptions to the adult eye and the CNS, including sensory neurons and the formation of the giant fiber system neural circuit.

Results

We performed a 2-stage genetic screen to identify mutations that modified phenotypes caused by over-expression of a dominant-negative Glued protein. We screened over 34,000 flies and isolated 41 mutations that enhanced or suppressed an eye phenotype. Of these, 12 were assayed for interactions in the giant fiber system by which they altered a giant fiber morphological phenotype and/or altered synaptic function between the giant fiber and the tergotrochanteral muscle motorneuron. Six showed interactions including a new allele of atypical protein kinase C (aPKC). We show that this cell polarity regulator interacts with Glued during central synapse formation. We have mapped the five other interacting mutations to discrete chromosomal regions.

Conclusion

Our results show that an efficient way to screen for genes involved in central synapse formation is to use a two-step strategy in which a screen for altered eye morphology precedes the analysis of central synaptogenesis. This has highlighted a role for aPKC in the formation of an identified central synapse.