bluuebunny/crossref_metadata_2025 huggingface dataset:
A Concept Analysis of Cultural Sensitivity
Authors: Foronda Cynthia L.
Published: April 2008

Cultural sensitivity is used ubiquitously, yet different meanings are constructed. An improved understanding of the term as described within health care and in general would enhance nurses' understanding and communication with professionals and clients. To uncover the current meaning of cultural sensitivity, a concept analysis was performed. Findings included the attributes of knowledge, consideration, understanding, respect, and tailoring. Necessary antecedents were diversity, awareness, and an encounter. The consequences were effective communication, effective intervention, and satisfaction. A definition of cultural sensitivity was proposed. Providers may benefit from recognizing and addressing the identified antecedents and attributes to obtain the positive consequences of employing cultural sensitivity.
Information Literacy and the Introductory Management Classroom
Authors: Leigh Jennifer S. A. , Gibbon Cynthia A.
Published: April 2008

This article proposes that the integration of information literacy standards into the management classroom can address underdeveloped student research strategies and promote effective use of print, digital, and free Web resources. Incorporating information literacy can support management educators in their need to balance disciplinary content, departmental curriculum, and broader educational goals that support the preparation of future managers. This article begins with a review of core information literacy concepts and standards. An in-depth discussion of information literacy challenges on campus and in the workplace follows. Next, the authors offer an evolving case example that illustrates the incorporation of information literacy skills and concepts into an introductory management course. Implications and suggestions for management educators are explored.
Efficient Parallel I/O in Community Atmosphere Model (CAM)
Authors: Tseng Yu-Heng , Ding Chris
Published: April 2008

Century-long global climate simulations at high resolutions generate large amounts of data in a parallel architecture. Currently, the community atmosphere model (CAM), the atmospheric component of the NCAR community climate system model (CCSM), uses sequential I/O which causes a serious bottleneck for these simulations. We describe the parallel I/O development of CAM in this paper. The parallel I/ O combines a novel remapping of 3-D arrays with the parallel netCDF library as the I/O interface. Because CAM history variables are stored in disk file in a different index order than the one in CPU resident memory because of parallel decomposition, an index reshuffle is done on the fly. Our strategy is first to remap 3-D arrays from its native decomposition to z-decomposition on a distributed architecture, and from there write data out to disk. Because z-decomposition is consistent with the last array dimension, the data transfer can occur at maximum block sizes and, therefore, achieve maximum I/ O bandwidth. We also incorporate the recently developed parallel netCDF library at Argonne/Northwestern as the collective I/O interface, which resolves a long-standing issue because netCDF data format is extensively used in climate system models. Benchmark tests are performed on several platforms using different resolutions. We test the performance of our new parallel I/O on five platforms (SP3, SP4, SP5, Cray X1E, BlueGene/L) up to 1024 processors. More than four realistic model resolutions are examined, e.g. EUL T85 (~1.4°), FV-B (2° × 2.5°), FV-C (1° × 1.25°), and FV-D (0.5° × 0.625°) resolutions. For a standard single history output of CAM 3.1 FV-D resolution run (multiple 2-D and 3-D arrays with total size 4.1 GB), our parallel I/O speeds up by a factor of 14 on IBM SP3, compared with the existing I/O; on IBM SP5, we achieve a factor of 9 speedup. The estimated time for a typical century-long simulation of FV D-resolution on IBM SP5 shows that the I/O time can be reduced from more than 8 days (wall clock) to less than 1 day for daily output. This parallel I/O is also implemented on IBM BlueGene/ L and the results are shown, whereas the existing sequential I/O fails due to memory usage limitation.
Identity, Contract and Enterprise in a Primary Care Setting: An English General Practice Case Study
Authors: McDonald Ruth , Harrison Stephen , Checkland Kath
Published: April 2008

This paper examines the responses of primary health care clinicians (doctors and nurses) to an invitation to enterprise contained in a new contract which offers financial rewards for meeting targets. We suggest that far from being swept along by a hegemonic enterprise discourse or having `no choice but to comply' (Cohen and Musson, 2000: 45), the engagement of our study participants in enterprising behaviours can be understood in terms of a more active process, albeit one characterized by new bureaucratic forms. Rather than riding roughshod over cherished traditional identities, part of the attraction of enterprise in our case study can be understood in terms of its role in assisting enterprising clinicians in managing the tensions inherent in these identities.
Parties and Leader Effects
Authors: Costa Lobo Marina
Published: April 2008

In this article, I analyse whether the electorate of different party types attributes different degrees of importance to leaders, as suggested by a recent party typology. Based on expert advice, 15 parties in six democracies were assigned to the following party types: class-mass, denominational and catch-all. Individual level data are used to determine the relative importance of leader effects for voters of different types of party vis-à-vis other explanatory factors. The article shows that there are indeed statistically significant differences in the importance of leader effects concerning mass-based parties (class-mass and denominational) and catch-all parties. Electors of mass-based parties are less sensitive to leaders than electors of catch-all parties at the ballot box. This is in accordance with previous studies in the party literature regarding the emphasis placed by different parties on the leader during election campaigns, and is an introduction to the nature of the party as a contextual factor of voting behaviour.
Factions, Parties and the Durability of Parliaments, Coalitions and Cabinets
Authors: Chambers Paul
Published: April 2008

Did Thailand's multiple parties and factions influence cabinet and coalition durability in the period 1979 to 2001? If so, which one — parties or factions — was the more significant? Taking a Transaction Costs Analysis approach, this article addresses these questions and argues that intra-party factions, as the building blocks of Thai parliamentary politics, have been more important than parties, such that each additional faction in a cabinet triggers a reduction in the longevity of prime ministerial terms and cabinets while affecting the durability of coalitions. Furthermore, while factions tend to shorten parliamentary and cabinet terms, they have the opposite effect on coalition terms. The study suggests that where parties are less cohesive, informal institutions within parties are of considerable importance.
The Political Representation of Ethnic Minorities
Authors: Togeby Lise
Published: April 2008

In general, ethnic minorities are strongly under-represented in representative bodies; however, there is no rule without exceptions. In the municipal elections in Denmark in 2001, the number of ethnic minorities who won election to the local councils throughout the country almost corresponded to their percentage in the general population. The explanation for this can be found in the Danish local election system, with its combination of proportional representation and preferential voting. This system is exceptionally conducive to collective mobilization, which results in a relatively high voter turnout among ethnic minorities and a fair representation in local councils. Since 1981, foreign citizens with permanent residence in Denmark have had the right to vote in local elections. This article describes the development in the representation of ethnic minorities since that time based on a study of all the municipalities in Denmark.
Factors Influencing the Decision of the Young Politically Engaged To Join a Political Party
Authors: Cross William , Young Lisa
Published: April 2008

Situated in the literature concerning the decline of party members, and the dearth of young party members, this article considers the factors that influence the decision of a politically engaged young person to join, or not join, a political party. Making use of a unique dataset, we examine the attitudes and socialization of a large group of politically active young Canadians, a group that includes a significant number of both party members and non-party members. The article finds significant attitudinal differences towards political parties, with non-members highly suspicious of parties in terms of their general democratic performance, their efficacy in achieving social and political change and in the ability of grassroots members to influence party decision-making. We also find important socialization effects, the most significant being that young party members are considerably more likely than non-members to have a parent who is a party member. Recruitment through family members appears to be a principal path to party membership for young voters.
The Christian Democratic Phoenix and Modern Unsecular Politics
Authors: van Kersbergen Kees
Published: April 2008

Christian democracy is still posing theoretical problems of definition and empirical puzzles of classification and interpretation. Analyses based on secularization theory produce puzzles and anomalies and have little to offer as explanations for the variation in Christian democratic power mobilization. Empirically, this article focuses on Christian democracy in The Netherlands and offers an explanation of the party's decline in the 1990s and its remarkable recovery. From this, lessons are drawn for further theory-building on party and party system change, and on Christian democracy. It seems that modern Christian democratic politics is evolving as neither religious nor secular, but as a version of unsecular politics.
What is game studies anyway?
Authors: Nieborg David B. , Hermes Joke
Published: April 2008

In this introduction, game studies is argued to be a force of innovation for cultural studies. While game studies, as it has developed over the last 10 years, fits well within cultural studies' methodology and theory, it does more than benefit from cultural studies as a 'mother discipline'. Game studies proves itself to be a strong force, especially in its productive use of political economy to analyse games and gaming as a (new) cultural form. Building on a descriptive taxonomy of games and gaming by both genre and 'platform', this is an introduction to games and gaming for those with a cultural studies background. While ideally, game studies will develop also as cultural critique, this is a far cry from dominant practice in the gamer community. Gamers tend to be 'hand-in-glove' with the industry. It is high time for game studies to turn a critical eye on itself.
The mod industries? The industrial logic of non-market game production
Authors: Nieborg David B. , van der Graaf Shenja
Published: April 2008

This article seeks to make the relationship between non-market game developers (modders) and the game developer company explicit through game technology. It investigates a particular type of modding, i.e. total conversion mod teams, whose organization can be said to conform to the high-risk, technologically-advanced, capital-intensive, proprietary practice of the developer company. The notion 'proprietary experience' is applied to indicate an industrial logic underlying many mod projects. In addition to a particular user-driven mode of cultural production, mods as proprietary extensions build upon proprietary technology and are not simple redesigned games, because modders tend to follow a particular marketing and industrial discourse with corresponding industrial-like practices.
Digital Arabs
Authors: Šisler Vít
Published: April 2008

This article presents the ways in which Muslims and Arabs are represented and represent themselves in video games. First, it analyses how various genres of European and American video games have constructed the Arab or Muslim Other. Within these games, it demonstrates how the diverse ethnic and religious identities of the Islamic world have been flattened out and reconstructed into a series of social typologies operating within a broader framework of terrorism and hostility. It then contrasts these broader trends in western digital representation with selected video games produced in the Arab world, whose authors have knowingly subverted and refashioned these stereotypes in two unique and quite different fashions. In conclusion, it considers the significance of western attempts to transcend simplified patterns of representation that have dominated the video game industry by offering what are known as 'serious' games.
Open invitation
Authors: Mäyrä Frans
Published: April 2008

Simultaneously lacking some fundamental data about the role of digital games in culture, while being faced with the challenge of games' near global presence, cultural game studies is in need of collaborative research efforts. This article discusses some starting points for cultural and social-psychological study of games and digital play, while inviting participation into an international, comparative research project.
Persona non grata: dilemmas of being an outsider researching immigration reform activism
Authors: Armitage Janet S.
Published: April 2008

Sociologists may encounter myriad obstacles in the research process that affect the research design and outcomes. There is, for example, a certain measure of resistance and hostility experienced in sociological research on distasteful social movements that is seldom acknowledged or included in published findings. The present analysis explores the emotional conflicts between the research program and the 'gatekeeping' activities of research respondents and the professional academic community in the USA. Politically sensitive, even volatile subjects such as the US immigration reform movement may rest on the classic affective/cognitive dichotomy found in sociology. I suggest that moralistic or politically positioned emotional resistance complicated the research process in two ways: 1) academic associates and mentors likened involvement with the immigration reform movement to scholarly complicity that marginalized the study's validity; and, 2) activists were inherently distrustful of the research and its goals given what they claimed to be a history of misinterpretation and scholarly 'bad press.'
Motives and social organization: sociological amnesia, psychological description and the analysis of accounts
Authors: Housley William , Fitzgerald Richard
Published: April 2008

During the course of this article we explore the sociological tradition of analysing motives and accounts. In doing so we contrast this with more recent methodological developments that have analysed similar phenomena as part of a strategy of respecifying psychological theories of cognition. Through the use of analytic examples we demonstrate how accounts and the invocation of 'inner' or 'underlying' states must be understood not only in terms of situated action but also in terms of the situated accomplishment of social organization. In this way the theoretical amnesia enveloping the analysis of accounts and motives can be confronted and their status as empirical sociological phenomena sustained within future avenues of qualitative research.
Transcendence, Liminality and Excess
Authors: Ramp William
Published: April 2008

Georges Bataille and Émile Durkheim stand within the same broad tradition of social and anthropological theory, and their work also displays structural affinities in the ways in which they pose questions concerning the definitions of science and relations between science and religion and in the manner in which they represent the process of social inquiry. Rather than using social science as a tool to explain religion as a mere object in a social field, they both, in their own ways, bring religion and science into a dangerous but fruitful proximity to each other, and engage them in a sort of mutual interrogation concerning the status of human being, autonomy and knowledge, and the constitution of social life and of meaning.
Indicating Commitment
Authors: Neubert Frank
Published: April 2008

By analysing two cases from the recent history of Vaishnavism (a temple festival in Vrindavan; the development of the International Society for Krishna Consciousness, or ISKCON), this paper shows that the notion of dépense as developed by Marcel Mauss, Robert Hertz and Georges Bataille can be applied as an analytical tool in the study of rituals and religion as an indicator of religious commitment. At the same time it is possible to show that, by constructing a kind of macro-economic theory that includes religious behaviour, recent theories of religious economics are part of, and reproduce, a modern discourse of rationality that rules out, rather than understands, forms of irrationality such as unproductive expenditure ( dépense).
The 6-Step Model for Community Empowerment: Revisited in Public Housing Communities for Low-Income Senior Citizens
Authors: Yoo Seunghyun , Butler James , Elias Thistle I. , Goodman Robert M.
Published: April 2008

The 6-step community empowerment model was replicated in communities with different geographical, racial, and age backgrounds from the original application. Resident groups of Blue Ribbon Health Panels (BRHPs) in federally funded senior housing in Pennsylvania followed the 6 steps to identify community health issues, to develop strategies to address priority issues, and to implement the strategies in collaboration with partner agencies. The 6-step model served as an operationalization strategy of community empowerment by facilitating quick accomplishments of communities' desired outcomes, legitimizing and motivating BRHP efforts. Community capacities to actively participate and collaborate influenced the model's progress in this replication study, as did partner agencies' capacities to adhere to the community-based participatory and collaborative orientation of the project. Community capacity development and partnership facilitation would be important for a community empowerment project, as well as consistent and clear communication among everyone involved in the process.
An Analytical Model for Calculating Thermal Bridge Effects in High Performance Building Enclosure
Authors: Tenpierik Martin , van Der Spoel Wim , Cauberg Hans
Published: April 2008

Although vacuum insulation panels (VIPs) are excellent thermal insulators, edge effects decrease their overall thermal performance. Moreover, they are often used with protections, such as integration into a panel. These panels typically use spacers that cause a significant additional thermal bridge. The effect of this thermal bridge is either determined accurately with numerical simulation tools or estimated with simple thermal resistance networks. The first approach is laborious, while the latter approach lacks accuracy. This study therefore presents and validates an analytical approximation model for calculating this thermal edge effect. A comparison of this model with numerical simulation shows that it can be applied with an inaccuracy of <10%. The total inaccuracy, however, also includes an error due to the schematization of the edge of the building panel. Yet, this model appears to be very useful for estimation of the linear thermal transmittance of the edge of building panels.
Estimating Values for the Moisture Source Load and Buffering Capacities from Indoor Climate Measurements
Authors: van Schijndel A.W.M.
Published: April 2008

The objective of this study is to investigate the potential for estimating values for the total size of human induced moisture source load and the total buffering (moisture storage) capacity of the interior objects with the use of relatively simple measurements and the use of heat, air, and moisture (HAM) models. The study presents the related modeling approaches, the implementation in the MatLab/ SimuLink environment, and a verification study of the models using indoor climate measurements of a Dutch museum. It is concluded that the modeling approach may be useful for estimating the magnitude of the human induced heat and moisture source loads. The case study is not usable for estimating the buffering capacity of the interior objects due to the weak dependency on the quantity of moisture storage material (there is almost no hygroscopic material present). However, the present approach has the side effect that it may be usable to indicate the effect of wet clothing. This study shows that the moisture source load of wet clothing per person can be of the same order as the moisture produced per person. Further research is needed if one wants to quantify the effect of wet clothing on the moisture load more accurately. More case studies are required to evaluate the approach for the determination of such moisture capacities.
Placenta growth factor augments endothelin-1 and endothelin-B receptor expression via hypoxia-inducible factor-1α
Authors: Patel Nitin , Gonsalves Caryn S. , Malik Punam , Kalra Vijay K.
Published: April 2008

Pulmonary hypertension (PHT) develops in sickle cell disease (SCD) and is associated with high mortality. We previously showed that erythroid cells produce placenta growth factor (PlGF), which activates monocytes to induce proinflammatory cytochemokines, contributing to the baseline inflammation and severity in SCD. In this study, we observed that PlGF increased expression of endothelin-1 (ET-1) and endothelin-B receptor (ET-BR) from human pulmonary microvascular endothelial cells (HPMVECs) and monocytes, respectively. PlGF-mediated ET-1 and ET-BR expression occurred via activation of PI-3 kinase, reactive oxygen species and hypoxia inducible factor-1α (HIF-1α). PlGF increased binding of HIF-1α to the ET-1 and ET-BR promoters; this effect was abrogated with mutation of hypoxia response elements in the promoter regions and HIF-1α siRNA and confirmed by chromatin immunoprecipitation analysis. Furthermore, PlGF-mediated ET-1 release from HPMVECs and ET-BR expression in monocytes creates a PlGF–ET-1–ET-BR loop, leading to increased expression of MCP-1 and IL-8. Our studies show that PlGF-induced expression of the potent vasoconstrictor ET-1 and its cognate ET-BR receptor occur via activation of HIF-1α, independent of hypoxia. PlGF levels are intrinsically elevated from the increased red cell turnover in SCD and in other chronic anemia (eg, thalassemia) and may contribute to inflammation and PHT seen in these diseases.
K-OPLS package: Kernel-based orthogonal projections to latent structures for prediction and interpretation in feature space
Authors: Bylesjö Max , Rantalainen Mattias , Nicholson Jeremy K , Holmes Elaine , Trygg Johan
Published: April 2008

Background

Kernel-based classification and regression methods have been successfully applied to modelling a wide variety of biological data. The Kernel-based Orthogonal Projections to Latent Structures (K-OPLS) method offers unique properties facilitating separate modelling of predictive variation and structured noise in the feature space. While providing prediction results similar to other kernel-based methods, K-OPLS features enhanced interpretational capabilities; allowing detection of unanticipated systematic variation in the data such as instrumental drift, batch variability or unexpected biological variation.

Results

We demonstrate an implementation of the K-OPLS algorithm for MATLAB and R, licensed under the GNU GPL and available athttp://www.sourceforge.net/projects/kopls/. The package includes essential functionality and documentation for model evaluation (using cross-validation), training and prediction of future samples. Incorporated is also a set of diagnostic tools and plot functions to simplify the visualisation of data, e.g. for detecting trends or for identification of outlying samples. The utility of the software package is demonstrated by means of a metabolic profiling data set from a biological study of hybrid aspen.

Conclusion

The properties of the K-OPLS method are well suited for analysis of biological data, which in conjunction with the availability of the outlined open-source package provides a comprehensive solution for kernel-based analysis in bioinformatics applications.
A probe-treatment-reference (PTR) model for the analysis of oligonucleotide expression microarrays
Authors: Ge Huanying , Cheng Chao , Li Lei M
Published: April 2008

Background

Microarray pre-processing usually consists of normalization and summarization. Normalization aims to remove non-biological variations across different arrays. The normalization algorithms generally require the specification of reference and target arrays. The issue of reference selection has not been fully addressed. Summarization aims to estimate the transcript abundance from normalized intensities. In this paper, we consider normalization and summarization jointly by a new strategy of reference selection.

Results

We propose a Probe-Treatment-Reference (PTR) model to streamline normalization and summarization by allowing multiple references. We estimate parameters in the model by the Least Absolute Deviations (LAD) approach and implement the computation by median polishing. We show that the LAD estimator is robust in the sense that it has bounded influence in the three-factor PTR model. This model fitting, implicitly, defines an "optimal reference" for each probe-set. We evaluate the effectiveness of the PTR method by two Affymetrix spike-in data sets. Our method reduces the variations of non-differentially expressed genes and thereby increases the detection power of differentially expressed genes.

Conclusion

Our results indicate that the reference effect is important and should be considered in microarray pre-processing. The proposed PTR method is a general framework to deal with the issue of reference selection and can readily be applied to existing normalization algorithms such as the invariant-set, sub-array and quantile method.
The influence of nicotine on granulocytic differentiation – Inhibition of the oxidative burst and bacterial killing and increased matrix metalloproteinase-9 release
Authors: Xu Minqi , Scott James E , Liu Kan-Zhi , Bishop Hannah R , Renaud Diane E , Palmer Richard M , Soussi-Gounni Abdel , Scott David A
Published: April 2008

Background

Neutrophils leave the bone marrow as terminally differentiated cells, yet little is known of the influence of nicotine or other tobacco smoke components on neutrophil differentiation. Therefore, promyelocytic HL-60 cells were differentiated into neutrophils using dimethylsulfoxide in the presence and absence of nicotine (3-(1-methyl-2-pyrrolidinyl) pyridine). Differentiation was evaluated over 5 days by monitoring terminal differentiation markers (CD11b expression and formazan deposition); cell viability, growth phase, kinetics, and apoptosis; assessing cellular morphology and ultrastructure; and conformational changes to major cellular components. Key neutrophil effector functions (oxidative burst, bacterial killing, matrix metalloproteinase release) were also examined.

Results

Nicotine increased the percentage of cells in late differentiation phases (metamyelocytes, banded neutrophils and segmented neutrophils) compared to DMSO alone (p < 0.05), but did not affect any other marker of neutrophil differentiation examined. However, nicotine exposure during differentiation suppressed the oxidative burst in HL-60 cells (p < 0.001); inhibited bacterial killing (p < 0.01); and increased the LPS-induced release of MMP-9, but not MMP-2 (p < 0.05). These phenomena may be α-7-acetylcholine nicotinic receptor-dependent. Furthermore, smokers exhibited an increased MMP-9 burden compared to non-smokers in vivo (p < 0.05).

Conclusion

These findings may partially explain the known increase in susceptibility to bacterial infection and neutrophil-associated destructive inflammatory diseases in individuals chronically exposed to nicotine.
Low prevalence of Chlamydia trachomatisinfection in asymptomatic young Swiss men
Authors: Baud David , Jaton Katia , Bertelli Claire , Kulling Jean-Pierre , Greub Gilbert
Published: April 2008

Background

Prevalence and risk factors for Chlamydia trachomatis infection among young men in Switzerland is still unknown. The objective of the present study was to assess prevalence and risk factors for C. trachomatis infection in young Swiss men.

Methods

517 young Swiss men were enrolled in this cross-sectional study during their compulsory military recruitment. Participants completed a questionnaire and gave urine samples which were screened for C. trachomatis DNA by PCR. Genotyping of positive samples was done by amplification and sequencing the ompA gene.

Results

The prevalence of chlamydial infection among young Swiss male was 1.2% (95% confidence interval [95%CI], 0.4–2.5%). C. trachomatis infection was only identified among the 306 men having multiple sexual partner. Although frequent, neither unprotected sex (absence of condom use), nor alcohol and drug abuse were associated with chlamydial infection. Men living in cities were more frequently infected (2.9%, 95%CI 0.8–7.4%) than men living in rural areas (0.5%, 95%CI 0.1–1.9%, p = 0.046). Moreover, naturalised Swiss citizens were more often positive (4.9%, 95%CI 1.3–12.5%) than native-born Swiss men (0.5%, 95%CI 0.1–1.7%, p = 0.003).

Conclusion

In comparison with other countries, the prevalence of chlamydial infection in men is extremely low in Switzerland, despite a significant prevalence of risky sexual behaviour. C. trachomatis infection was especially prevalent in men with multiple sexual partners. Further research is required (i) to define which subgroup of the general population should be routinely screened, and (ii) to test whether such a targeted screening strategy will be effective to reduce the prevalence of chlamydial infection among this population.
A novel c.5308_5311delGAGA mutation in Senataxin in a Cypriot family with an autosomal recessive cerebellar ataxia
Authors: Nicolaou Paschalis , Georghiou Anthi , Votsi Christina , Middleton Lefkos T , Zamba-Papanicolaou Eleni , Christodoulou Kyproula
Published: April 2008

Background

Senataxin (chromosome 9q34) was recently identified as the causative gene for an autosomal recessive form of Ataxia (ARCA), termed as Ataxia with Oculomotor Apraxia, type 2 (AOA2) and characterized by generalized incoordination, cerebellar atrophy, peripheral neuropathy, "oculomotor apraxia" and increased alpha-fetoprotein (AFP). Here, we report a novel Senataxin mutation in a Cypriot ARCA family.

Methods

We studied several Cypriot autosomal recessive cerebellar ataxia (ARCA) families for linkage to known ARCA gene loci. We linked one family (909) to the SETX locus on chromosome 9q34 and screened the proband for mutations by direct sequencing.

Results

Sequence analysis revealed a novel c.5308_5311delGAGA mutation in exon 11 of the SETX gene. The mutation has not been detected in 204 control chromosomes from the Cypriot population, the remaining Cypriot ARCA families and 37 Cypriot sporadic cerebellar ataxia patients.

Conclusion

We identified a novel SETX homozygous c.5308_5311delGAGA mutation that co-segregates with ARCA with cerebellar atrophy and raised AFP.
The influence of multi-morbidity and self-reported socio-economic standing on the prevalence of depression in an elderly Hong Kong population
Authors: Wong Samuel YS , Mercer Stewart W , Woo Jean , Leung Jason
Published: April 2008

Background

There has been an increasing prevalence of both depression and chronic medical conditions globally but the relationship between depression and multi-morbidity is not well understood. The aim of the present study was to investigate the relationship between depression, multi-morbidity (number of chronic medical conditions, and measures of socioeconomic standing (SES) in an elderly Hong Kong population.

Methods

Cross sectional study. Information on clinically relevant depressive symptoms, measured by the Geriatric Depression Scale (GDS), and demographic and chronic medical conditions were collected using standardized questionnaires. Information collected on SES included educational status (ES), maximum ever income (MEI), and self-perceived social standing in local community (SES-COM) and in Hong Kong generally (SES-HK). Analysis was conducted using multiple logistic regression

Results

Depression rates were similar in men and women (GDS caseness 8.1% vs 8.4%). Multi-morbidity of chronic medical conditions was common (40% of men and 46% of women had three or more). In the overall sample, the prevalence of depression was associated with the number of chronic medical conditions (OR 1.27; CI: 1.16–1.39). In addition, SES-HK and SES-COM were significant independent variables.

Conclusion

In this elderly Hong Kong population, depression prevalence rose markedly with number of chronic medical conditions and SES-HK and SES-COM.
Securing recruitment and obtaining informed consent in minority ethnic groups in the UK
Authors: Lloyd Cathy E , Johnson Mark RD , Mughal Shanaz , Sturt Jackie A , Collins Gary S , Roy Tapash , Bibi Rukhsana , Barnett Anthony H
Published: April 2008

Background

Previous health research has often explicitly excluded individuals from minority ethnic backgrounds due to perceived cultural and communication difficulties, including studies where there might be language/literacy problems in obtaining informed consent. This study addressed these difficulties by developing audio-recorded methods of obtaining informed consent and recording data. This report outlines 1) our experiences with securing recruitment to a qualitative study investigating alternative methods of data collection, and 2) the development of a standardised process for obtaining informed consent from individuals from minority ethnic backgrounds whose main language does not have an agreed written form.

Methods

Two researchers from South Asian backgrounds recruited adults with Type 2 diabetes whose main language was spoken and not written, to attend a series of focus groups. A screening tool was used at recruitment in order to assess literacy skills in potential participants. Informed consent was obtained using audio-recordings of the patient information and recording patients' verbal consent. Participants' perceptions of this method of obtaining consent were recorded.

Results

Recruitment rates were improved by using telephone compared to face-to-face methods. The screening tool was found to be acceptable by all potential participants. Audio-recorded methods of obtaining informed consent were easy to implement and accepted by all participants. Attrition rates differed according to ethnic group. Snowballing techniques only partly improved participation rates.

Conclusion

Audio-recorded methods of obtaining informed consent are an acceptable alternative to written consent in study populations where literacy skills are variable. Further exploration of issues relating to attrition is required, and a range of methods may be necessary in order to maximise response and participation rates.
Extracellular heat shock protein 70 inhibits tumour necrosis factor-α induced proinflammatory mediator production in fibroblast-like synoviocytes
Authors: Luo Xinjing , Zuo Xiaoxia , Zhou Yaou , Zhang Bing , Shi Yongzhong , Liu Meidong , Wang Kangkai , McMillian D Randy , Xiao Xianzhong
Published: April 2008

Introduction

It was recently suggested that heat shock protein (HSP)70, an intracellular protein, is a potential mediator of inflammatory disease when it is released into the extracellular compartment. Although elevated HSP70 levels have been identified in rheumatoid arthritis (RA) synovial tissues and RA synovial fluid compared with patients with osteoarthritis and healthy individuals, it remains unclear what role extracellular HSP70 plays in the pathogenesis of RA. This study was conducted to investigate the effects of extracellular HSP70 on the production of RA-associated cytokines in fibroblast-like synoviocytes from patients with RA and to elucidate the mechanisms involved.

Methods

IL-6, IL-8 and monocyte chemoattractant protein (MCP)-1 levels in culture supernatants were measured using enzyme-linked immunosorbent assays. Activation of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated protein kinases (ERKs), c-Jun amino-terminal kinase (JNK) and p38 MAPK, was detected using Western blotting. Nuclear translocation of nuclear factor-κB (NF-κB) and degradation of the inhibitory protein IκBα were examined using immunohistochemistry and Western blotting.

Results

Human HSP70 downregulated IL-6, IL-8 and MCP-1 production in RA fibroblast-like synoviocytes induced by tumour necrosis factor (TNF)-α in a concentration dependent manner. HSP70 inhibited the activation of ERK, JNK and p38 MAPK in fibroblast-like synoviocytes stimulated by TNF-α. Furthermore, HSP70 also significantly inhibited nuclear translocation of nuclear factor-κB and degradation of IκBα induced by TNF-α.

Conclusion

Extracellular HSP70 has an anti-inflammatory effect on RA by downregulating production of IL-6, IL-8 and MCP-1 in fibroblast-like synoviocytes, which is mediated through inhibited activation of the MAPKs and NF-κB signal pathways.
Genomic degradation of a young Y chromosome in Drosophila miranda
Authors: Bachtrog Doris , Hom Emily , Wong Karen M , Maside Xulio , de Jong Pieter
Published: April 2008

Background

Y chromosomes are derived from ordinary autosomes and degenerate because of a lack of recombination. Well-studied Y chromosomes only have few of their original genes left and contain little information about their evolutionary origin. Here, we take advantage of the recently formed neo-Y chromosome of Drosophila miranda to study the processes involved in Y degeneration on a genomic scale.

Results

We obtained sequence information from 14 homologous bacterial artificial chromosome (BAC) clones from the neo-X and neo-Y chromosome of D. miranda, encompassing over 2.5 Mb of neo-sex-linked DNA. A large fraction of neo-Y DNA is composed of repetitive and transposable-element-derived DNA (20% of total DNA) relative to their homologous neo-X linked regions (1%). The overlapping regions of the neo-sex linked BAC clones contain 118 gene pairs, half of which are pseudogenized on the neo-Y. Pseudogenes evolve significantly faster on the neo-Y than functional genes, and both functional and non-functional genes show higher rates of protein evolution on the neo-Y relative to their neo-X homologs. No heterogeneity in levels of degeneration was detected among the regions investigated. Functional genes on the neo-Y are under stronger evolutionary constraint on the neo-X, but genes were found to degenerate randomly on the neo-Y with regards to their function or sex-biased expression patterns.

Conclusion

Patterns of genome evolution in D. miranda demonstrate that degeneration of a recently formed Y chromosome can proceed very rapidly, by both an accumulation of repetitive DNA and degeneration of protein-coding genes. Our data support a random model of Y inactivation, with little heterogeneity in degeneration among genomic regions, or between functional classes of genes or genes with sex-biased expression patterns.
Intensive Chemotherapy Followed by Hematopoietic Stem-Cell Rescue for Refractory and Recurrent Primary CNS and Intraocular Lymphoma: Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire
Authors: Soussain Carole , Hoang-Xuan Khê , Taillandier Luc , Fourme Emmanuelle , Choquet Sylvain , Witz Francis , Casasnovas Olivier , Dupriez Brigitte , Souleau Bertrand , Taksin Anne-Laure , Gisselbrecht Christian , Jaccard Arnaud , Omuro Antonio , Sanson Marc , Janvier Maud , Kolb Brigitte , Zini Jean-Marc , Leblond Véronique
Published: April 2008

Purpose

The prognosis of relapsing primary CNS lymphoma (PCNSL) is poor. We report the results of a prospective multicenter trial of intensive chemotherapy followed by autologous hematopoietic stem-cell rescue (IC + HCR) in immunocompetent adult patients with PCNSL or intraocular lymphoma (IOL) after failure of high-dose methotrexate-based treatment.

Patients and Methods

Salvage treatment consisted of two cycles of high-dose cytarabine and etoposide (CYVE). Intensive chemotherapy combined thiotepa, busulfan, and cyclophosphamide. Forty-three patients (median age, 52 years; range, 23 to 65 years) were included, with relapse (n = 22), refractory disease (n = 17), or a partial response to first-line treatment (n = 4). The response to CYVE was not assessable in three cases because of treatment-related death. Twenty patients (47%) were chemosensitive to CYVE: 15 of them proceeded to IC + HCR. IC + HCR was also administered to 12 patients who did not respond to CYVE. All but one of the 27 patients who underwent IC + HCR entered complete remission.

Results

With a median follow-up of 36 months, the median overall survival was 18.3 months in the overall population, and 58.6 months among patients who completed IC + HCR. The respective median progression-free survival (PFS) times after IC + HCR were 11.6 and 41.1 months. The 2-year overall survival probability was 45% in the whole population and 69% among the 27 patients who received IC + HCR. The 2-year PFS probability was 43% among all the patients and 58% in the IC + HCR subpopulation.

Conclusion

IC + HCR is an effective treatment for refractory and recurrent PCNSL.
TbG63, a golgin involved in Golgi architecture inTrypanosoma brucei
Authors: Ramirez Irene Barinaga-Rementeria , de Graffenried Christopher L. , Ebersberger Ingo , Yelinek Jordan , He Cynthia Y. , Price Albert , Warren Graham
Published: April 2008

Golgins are coiled-coil proteins that have been implicated in the structure and function of the Golgi complex. Here, we identify and characterize a trypanosomal golgin, TbG63, showing that it has a C-terminal membrane anchor and an N-terminus that projects into the cytoplasm. TbG63 in procyclic parasites is localized to the Golgi and interacts with the active, GTP-form of TbRab1A. Overexpression of TbG63 has dramatic effects on Golgi architecture – effects that require the N-terminus – whereas depletion has little, if any, effect on the growth rate. By contrast, in the bloodstream form of the parasite, depletion of TbG63 slows growth, although it has no obvious effect on the transport of a variant surface glycoprotein (VSG) or on Golgi structure. TbG63 might be a useful tool to study the structure and functioning of the Golgi complex.
Dynamic analysis identifies novel roles for DLG-1 subdomains in AJM-1 recruitment and LET-413-dependent apical focusing
Authors: Lockwood Christopher A. , Lynch Allison M. , Hardin Jeff
Published: April 2008

Cell-cell junctions are composed of a diverse array of specialized proteins that are necessary for the movement and integrity of epithelia. Scaffolding molecules, such as membrane-associated guanylate kinases (MAGUKs) contain multiple protein-protein interaction domains that integrate these proteins into macromolecular complexes at junctions. We have used structure-function experiments to dissect the role of domains of the Caenorhabditis elegans MAGUK DLG-1, a homolog of Drosophila Discs large and vertebrate SAP97. DLG-1 deletion constructs were analyzed in directed yeast two-hybrid tests as well as in vivo in a dlg-1 null mutant background. Our studies identify novel roles for several key domains. First, the L27 domain of DLG-1 mediates the physical interaction of DLG-1 with its binding partner, AJM-1, as well as DLG-1 multimerization. Second, the PDZ domains of DLG-1 mediate its association with the junction. Third, using dynamic in vivo imaging, we demonstrate that the SH3 domain is required for rapid lateral distribution of DLG-1 via a LET-413/Scribble-dependent pathway. Finally, we found that inclusion of the SH3 domain can ameliorate dlg-1 mutant phenotypes, but full rescue of lethality required the complete C terminus, which includes the GUK and Hook domains, thereby demonstrating the importance of the C-terminus for DLG-1 function. Our results represent the first in vivo analysis of requirements for the L27 domain of a Discs-large/SAP97 protein, identify a crucial LET-413/Scribble regulatory motif and provide insight into how MAGUK subdomains function to maintain epithelial integrity during development.
Organellar dynamics during the cell cycle of Toxoplasma gondii
Authors: Nishi Manami , Hu Ke , Murray John M. , Roos David S.
Published: April 2008

The protozoan phylum Apicomplexa encompasses ∼5000 species of obligate intracellular parasites, including those responsible for malaria and toxoplasmosis. Rather than dividing by binary fission, apicomplexans use a remarkable mechanism for replication, assembling daughters de novo within the cytoplasm. Here, we exploit time-lapse microscopy of fluorescent markers targeted to various subcellular structures in Toxoplasma gondii tachyzoites to determine how these unicellular eukaryotes efficiently package a complete set of organelles, maintaining the highly polarized organization necessary for host cell invasion and pathogenesis. Golgi division and elongation of the apicoplast are among the first morphologically observable events, associated with an unusual pattern of centriolar migration. Daughter parasites are assembled on cytoskeletal scaffolding, whose growth proceeds from the apical end, first encapsulating the divided Golgi. Further extension of the cytoskeletal scaffold results in partitioning of the apicoplast, nucleus, endoplasmic reticulum, and finally the mitochondrion, which enters the developing daughters rapidly, but only very late during the division cycle. The specialized secretory organelles (micronemes and rhoptries) form de novo. This distinctive pattern of replication – in which organellar segregation spans ∼75% of the cell cycle, completely encompassing S phase – suggests an unusual mechanism of cell cycle regulation.
Repugnance as a Constraint on Markets
Authors: Roth Alvin E
Published: April 2008

This essay examines how repugnance sometimes constrains what transactions and markets we see. When my colleagues and I have helped design markets and allocation procedures, we have often found that distaste for certain kinds of transactions is a real constraint, every bit as real as the constraints imposed by technology or by the requirements of incentives and efficiency. I'll first consider a range of examples, from slavery and indentured servitude (which are much more repugnant now than they once were) to lending money for interest (which used to be widely repugnant but no longer is), and from bans on eating horse meat in California to bans on dwarf tossing in France. An example of special interest will be the widespread laws against the buying and selling of organs for transplantation. The historical record suggests that while repugnance can change over time, it can persist for a very long time, although changes in institutions that reflect repugnance can occur relatively quickly when the underlying repugnance changes.