bluuebunny/crossref_metadata_2025 huggingface dataset:
The Application of an Institutional Clinical Data Warehouse to the Assessment of Adverse Drug Reactions (ADRs)
Authors: Zhang Q. , Teratani T. , Yoshimoto S. , Mineno T. , Nakagawa K. , Nagahama M. , Kuwata S. , Takeda H. , Matsumura Y.
Published: September 2007

Objectives:
To apply an institutional clinical data warehouse (CDW) to the assessment of adverse drug reactions (ADRs) and demonstrate its utility through a specific example.

Methods:
We modeled the process for assessing ADRs through retrospective cohort design by using CDW at the Osaka University Hospital as follows: 1) We defined a drug X, an adverse drug reaction (ADR) Y, and a laboratory measurement Z to assess Y during a given study period; 2) we excluded those whose Z value exceeded the defined criteria or were not available at the inception of the cohort; 3) we divided the patients into two groups based on exposure or non-exposure to X; 4) we matched the patient characteristics between the two groups through stratification and randomization; and 5) we compared the frequency of patients who presented Y during the study period between the two groups. Aminoglycoside and Cephalosporin associated nephrotoxicity in pediatric inpatients was used as an example to demonstrate the usefulness of this approach.

Results:
Our evaluation indicates that there is an increased risk of nephrotoxicity for pediatric inpatients who were prescribed cephalosporin either alone or in combination with aminoglycoside; further, aminoglycoside tends to increase the cephalosporin-associated nephrotoxicity.

Conclusions:
Our findings are consistent with those drawn from other studies, indicating thatthe method of a pplying an institutional CDW is useful for assessing ADRs.
Pseudo-precision in Gene Expression Values Can Reduce Efficiency
Authors: Boes T. , Jöckel K.-H. , Neuhäuser M.
Published: September 2007

Objectives:
When estimating the expression of genes based on the scanned images from microarrays various algorithms are applied in a so-called low-level analysis which can calculate expression values with an arbitrary number of digits beyond the decimal point. However, too many digits (decimal places) are usually not justified because they do not represent the precision of the measured expression. Thus, there is pseudo-precision and, as a result, there are no tied values.

Methods:
We suggest avoiding, or omitting, the pseudo-precision: ties can remain, or be created by rounding the computed expression values. Then, average ranks can be used in order to apply nonparametric tests when ties occur. We use two actual data sets and the Wilcoxon rank sum test.

Results:
We demonstrate that rounding gives a more efficient test, i.e. the average p-value is decreased and the number of p-values smaller than 0.05 is increased.

Conclusions:
The random noise of pseudo-precision can reduce the efficiency of statistical tests applied to detect differentially expressed genes. This result is, obviously, relevant in many other areas of our digitalized world.
Accurate Variance Estimation for Prevalence Ratios
Authors: Bruckner T. , Schumacher M. , Wolkewitz M.
Published: September 2007

Objectives:
The log-binomial model is recommended for calculating the prevalence ratio in cross-sectional studies with binary outcomes. However, convergence problems may occur as this model is numerically unstable. If this happens, the Poisson model should be used, but the Poisson model variance needsto be adjusted. Here, we compare different adjustments.

Methods:
Using simulation we evaluated the performance of Poisson models with i) a robust variance, ii) the scale parameter adjusted by Pearson’s chi-square, and iii) the scale parameter adjusted by the deviance. These models were compared with the log-binomial model with respectto hypothesis testing. Confounding and effect modification are considered.

Results:
All adjustment models improved the variance estimation. The Poisson model with a robust variance performed best. When the log-binomial model is numerically stable as well as unstable, this model yields reasonable power and type I error values. But the Poisson model with the scale parameter adjusted by Pearson’s chi-square also showed good results.

Conclusions:
When estimating prevalence ratios, if the log-binomial fails to converge, we recommend the Poisson modelwith a robust estimate of variance.
Event Oriented Representation for Collaborative Activities (EORCA)
Authors: Bonnardel N. , Antonini F. , Albanese J. , Martin C. , Chaudet H. , Pellegrin L.
Published: September 2007

Objectives:
In this paper, we introduce a method that aims at describing components of medical activities that are performed by a medical team, including physicians and nurses, during patients’ management in an ICU (intensive care unit). This method is based on formal taskanalyses developed in cognitive ergonomics.

Our ultimate aim is to build a method covering the observation and the representation of collective activities during patients’ management, which should be re-usable by the team members in order to prepare themselvesfor accreditation.

Methods:
This method comprises two main steps: – the formal observations of medical staff’s activities that occur during patient management, -a representation of the findings with regard to an ontology and a temporal flowchart, which describes actors and events related to patient management.

Results:
This paper describes field studies performed in ICUs. This method has been used for analyzing the management of 24 cases of neurological and multiple traumas. We have represented the different actions of the medical team members (clinicians, nurses and outside medical consultants).

Conclusion:
The results allow us to identify the specific features of these complexand time-constrained situations, especially about the strong collaborative activities between members of the patient-care teams, especially the interaction between information management and medical actions.
New Bioinformatic Strategies to Rapidly Characterize Retroviral Integration Sites of Gene Therapy Vectors
Authors: Giordano F. A. , Hotz-Wagenblatt A. , Lauterborn D. , Appelt J.-U. , Fellenberg K. , Nagy K. Z. , Zeller W. J. , Suhai S. , Fruehauf S. , Laufs S.
Published: September 2007

Objective:
Increasing use of retroviral vector-mediated gene transfer created intense interest to characterize vector integrations on the genomic level. Techniques to determine insertion sites, mainly based on time-consuming manual data processing, are commonly applied. Since a high variability in processing methods hampers further data comparison, there is an urgent need to systematically process the data arising from such analysis.

Methods:
To allow large-scale and standardized comparison of insertion sites of viral vectors we developed two programs, IntegrationSeqand IntegrationMap. IntegrationSeq can trim sequences, and valid integration sequences get further processed with IntegrationMap for automatic genomic mapping. IntegrationMap retrieves detailed information about whether integrations are located in or close to genes, the name of the gene, the exact localization in the transcriptional units, and further parameters like the distance from the transcription start site to the integration.

Results:
We validated the method using 259 files originating from integration site analysis (LM-PCR). Sequences processed by IntegrationSeq led to an increased yield of valid integration sequence detection, which were shown to be more sensitive than conventional analysis and 15 times faster, while the specificities are equal. Output files generated by IntegrationMap were found to be 99.8% identical with results retrieved by much slower conventional mapping with the ENSEMBL alignment tool.

Conclusion:
Using IntegrationSeq and IntegrationMap, a validated, fast and standardized high-throughput analysis of insertion sites can be achieved for the first time.
Towards New Scopes: Sensor-enhanced Regional Health Information Systems
Authors: Marschollek M. , Wolf K.-H. , Haux R. , Bott O. J.
Published: September 2007

Objectives:
To analyze utilization of sensor technology in telemonitoring and home care and to discuss concepts and challenges of sensor-enhanced regional health information systems (rHIS).

Methods:
The study is based upon experience in sensor-based telemedicine and rHIS projects, and on an analysis of HIS-related journal publications from 2003 to 2005 conducted in the context of publishing the IMIA Yearbook of Medical Informatics.

Results:
Health-related parameters that are subject to sensor-based measurement in home care and tele-monitoring are identified. Publications related to tele-monitoring, home care and smart houses are analyzed concerning scope and utilization of sensor technology. Current approaches for integrating sensor technology in rHIS based on a corresponding eHealth infrastructure are identified. Based on a coarse architecture of home care and telemonitoring systems ten challenges for sensor-enhanced rHIS are identified and discussed: integration of home and health telematic platforms towards a sensor-enhanced telematic platform, transmission rate guarantees, ad hoc connectivity, cascading data analysis, remote configuration, message and alert logistic, sophisticated user interfaces, unobtrusiveness, data safety and security, and electronic health record integration.

Conclusions:
Utilization of sensor technology in health care is an active field of research. Currently few research projects and standardization initiatives focus on general architectural considerations towards suitable telematic platforms for establishing sensor-enhanced rHIS. Further research finalized by corresponding standardization is needed. Part 2 of this paperwill present experiences with a research prototype for a sensor-enhanced rHIS telematic platform.
Expanding the Scope of Health Information Systems
Authors: Giuse D. A. , Lapão L. , Wurst S. H. R. , Kuhn K. A.
Published: September 2007

Objectives:
To identify current developments, obstacles, and opportunities for health information systems.

Methods:
International reports werediscussed during an IMIA HIS Working Conference with a focus on architectural design, project goals and drivers, obstacles, and opportunities.

Results:
Technology and standards are available to build regional and national health IT networks, and successful implementations are currently being realized. There is, however, little consensus and communication concerning goals, benefits and risks of large-scale health IT initiatives. Complexity tends to be underestimated, and the public needs to be more involved in the decision-making process.

Conclusion:
On all levels and across borders, a climate of exchange of ideas, experiences – both successes and failures-, policies, standards, systems, and information should be created.
Attributable Mortality due to Nosocomial Infections
Authors: Wangler M. , Wolkewitz M. , Beyersmann J. , Schumacher M.
Published: September 2007

Objectives:
Nosocomial infections constitute a major medical problem leading to increased morbidity and mortality of patients. Besides prolongation of length of hospital stay, hospital mortality attributable to those infections is often the quantity of interest when describing their impact and consequences. Since occurrence of nosocomial infections is a time-dynamic process, estimation of this quantity might be hampered by that fact. A general frameworkshall be developed for defining and estimating attributable mortality that in addition is taking discharge of patients as competing risk and potential censoring of observation time into account.

Methods:
Since the term “attributable mortality” is used in a variety of meanings we first review basic definitions; the quantities of interest are then derived in terms of transition probabilities arising in a suitably defined multistate model that allows straightforward estimation and interpretation. Bootstrap resampling is used to calculate corresponding standard errors and confidence intervals.

Results:
The methodology is applied to the data of the SIR-3 study, a prospective cohort study on the incidence of nosocomial infections in intensive care unit patients. Occurrence of nosocomial pneumonia is shown to be associated with increased mortality; the population-attributable fraction is estimated as 7.7% (95% confidence interval: 2.6-12.8%) for an observation period of 120 days.

Conclusion:
Attributable mortality is an important risk measure in epidemiology. If risk exposure is time-dependent, multistate models provide an easily understandable framework to define and estimate attributable mortality. The approach is capable of handling competing events, which are omnipresent in clinical research and censoring.
Pitx2c
and
Nkx2-5
Are Required for the Formation and Identity of the Pulmonary Myocardium
Authors: Mommersteeg Mathilda T.M. , Brown Nigel A. , Prall Owen W.J. , de Gier-de Vries Corrie , Harvey Richard P. , Moorman Antoon F.M. , Christoffels Vincent M.
Published: September 2007

The pulmonary vein is sleeved by myocardium, which is a major source of atrial fibrillation and is involved in congenital sinus venosus defects. Little is known about the cellular origin and mechanism of formation of the pulmonary myocardium. We observed a biphasic process of pulmonary myocardium formation in mice. Firstly, a myocardial cell population forms de novo at the connection of the pulmonary vein and the atrium. Genetic labeling revealed that atrial cells do not contribute to this population, indicating it forms by differentiation of pulmonary mesenchymal cells. Secondly, these pulmonary myocardial cells initiate a phase of rapid proliferation and form the pulmonary myocardial sleeve.
Pitx2c
-deficient mice do not develop a pulmonary myocardial sleeve because they fail to form the initial pulmonary myocardial cells. Genetic-labeling analyses demonstrated that whereas the systemic venous return derives from
Nkx2-5
–negative precursors, the pulmonary myocardium derives from
Nkx2-5
–expressing precursors, indicating a distinct origin of the 2 venous systems.
Nkx2-5
and its target gap-junction gene
Cx40
are expressed in the atria and in the pulmonary myocardium but not in the systemic venous return, which expresses the essential pacemaker channel
Hcn4
. When Nkx2-5 protein level was lowered in a hypomorphic model, the pulmonary myocardium switched to a
Cx40
-negative,
Hcn4
-positive phenotype resembling that of the systemic venous return. In conclusion, our data suggest a cellular mechanism for pulmonary myocardium formation and highlight the key roles played by Pitx2c and Nkx2-5 in its formation and identity.
Latino Self-Employment and Entrepreneurship in the United States: An Overview of the Literature and Data Sources
Authors: Robles Bárbara J. , Cordero-Guzmán Héctor
Published: September 2007

While significant attention has been paid to the growth of the Latino population and its contribution to the U.S. labor market, less scholarly and popular media attention has focused on Latino self-employment, entrepreneurship, and business growth. A review of interdisciplinary research literature on Latino entrepreneurship over the past twenty-five years indicates a gap in our knowledge about the accelerated growth in Latino small business ownership across the United States. The authors provide an overview of the current state of research on Latino entrepreneurial activities and recommend a broader research agenda that includes community-based organizations as part of the entrepreneurship landscape in urban and rural high-density Latino communities.
Building Ventures through Civic Capitalism
Authors: Brush Candida , Monti Daniel , Ryan Andrea , Gannon Amy M.
Published: September 2007

An exploratory study of urban entrepreneurs participating in a technical assistance program finds that they focus on the bottom line and often have an explicit wish to improve their community. This integrated combination of economic and social values, a kind of civic-minded capitalism, guides their positioning for growth and yields a business that can best be called a “civic enterprise.” A descriptive analysis of qualitative and quantitative research yields propositions for future research on these hybrid business ventures.
A Modification to Angoff and Bookmarking Cut Scores to Account for the Imperfect Reliability of Test Scores
Authors: MacCann Robert G.
Published: September 2007

It is shown that the Angoff and bookmarking cut scores are examples of true score equating that in the real world must be applied to observed scores. In the context of defining minimal competency, the percentage ``failed'' by such methods is a function of the length of the measuring instrument. It is argued that this length is largely arbitrary, being heavily influenced by practical educational constraints. Hence, there is an ambiguity or nonuniqueness about the percentage failed. An argument is advanced that the failure rate should reflect the percentage of true scores below the cut score. A modification to the cut score is derived that achieves this outcome and simultaneously removes the nonuniqueness in the percentage failed.
`Am I not a Man and a Brother?' The Bible and the British Anti-Slavery Campaign
Authors: Barclay John M. G.
Published: September 2007

After surveying the use of the Bible on behalf of slave-owners, this article studies the biblical exegesis employed by Porteus, Sharp, Hughes and others in the British anti-slavery movement. The decisive hermeneutical move was the recategorization of the slave as a man/woman and a brother/sister — part of a larger intellectual shift in philosophy and theology. The specific contribution of evangelical theology is noted in this connection.
The History of Ancient Israel and Judah
Authors: Davies Philip
Published: September 2007

Writing a `history of Israel' is a task that is vastly different to writing history of modern events, yet this distinction is often not recognized. There are limitations in the written sources, the archaeological record is unable to locate a `biblical Israel' in differentiation from the various cultures that inhabited Palestine in the same period and the bible itself was written with a particular theological agenda many centuries after the events it purports to report. Rather what is preserved in the biblical texts is a collection of snapshots of how Israel has been remembered. This `cultural history' allows for the appropriation of the stories of communities of faith. It is within such layers of memory that the resources can be found to refashion the understanding of the biblical story in a way that finds meaning for successive generations.
The Anxiety of Influences: Dis-Locating Authority, Culture and Identity in the Novels of Colin Cheong
Authors: Goh Robbie B. H.
Published: September 2007

In its rapid socio-economic transformation over the four decades or so of its existence as an independent nation and in its quest to position itself as a competitive global nation and service hub, Singapore has come to embody many of the cultural phenomena of Asian modernity in an age of globalization. This has imposed a number of cultural, narrative and ideological influences on its writers. Young “post-65” Anglophone Chinese novelists like Colin Cheong, while occupying a relatively privileged position in a much more affluent Singapore society than that occupied by Singaporean writers of an older generation, position themselves against the paternalistic authority of the establishment, and at the nexus of a variety of global cultural influences. The result is a thematics and narratology of restlessness itself, which might thus be seen as the governing trope of Singapore Anglophone literary production in an age of globalization.
Women, Time and Place in Fiona Kidman's The Book of Secrets
Authors: D' Cruz Doreen
Published: September 2007

This essay explores the strategies whereby a female fictional historiography intercepts patriarchy's ownership of “sign and time” and alters the configurations of official history. Fiona Kidman's narrative covering three generations of women linked to the diasporic community initially headed by Norman McLeod is deemed to formulate its challenge to received linear history through a dialogic process consistent with Bakhtin's elaboration of this notion. This essay further argues that through its juxtaposition of the emergent counter-history alongside lyric time associated with maternal processes, Kidman's novel rejects the binary opposition between nature and culture, lyric and narrative, which patriarchy has used in order to deny women a place in the cultural continuum. It also contends that the female contestation of history is enabled through places, best exemplified by the house at Waipu, where women can constitute themselves as mothers as well as daughters to mothers. Thus the place of female exclusion and incarceration doubles as a sanctuary and archival resource from where competing feminist constructions are mounted.
Coetzee's Disgrace: Byron in Italy and the Eastern Cape c. 1820
Authors: Easton Kai
Published: September 2007

Despite the prominence of Coetzee's prize-winning novel Disgrace (1999) in discussions of “new” South African fiction, to date there has been little interest in examining either Coetzee's choice of landscape in this novel, or the literary-biographical sub-plot of his Romantic scholar protagonist, David Lurie. What does the colonial history of British settlement have to do with Coetzee's pointedly new South African novel? And how does the story of Byron's exile in Italy relate to the province that — since 1994 — we officially call the Eastern Cape? In this essay, I discuss these two seemingly unrelated plots, locating Disgrace in the “Discourse of the Cape” that he writes about in his seminal book of essays, White Writing (1988), together with selected and relevant facts from the life and times of Lord Byron. I argue that, by featuring Byron during his time in Italy, Coetzee's novel highlights a radical romanticism, which offers a challenge to the British romantic tradition that simultaneously established itself at the Cape c. 1820, and still has resonance today.
Marcel Gauchet, Pierre-André Taguieff and the question of democracy in France
Authors: Flood Christopher
Published: September 2007

As its starting-point this article situates the new reactionaries controversy in relation to recent intellectual debates on the alleged national crisis of confidence in France's political and social models. The political ideas of Marcel Gauchet and Pierre-André Taguieff, two of the leading figures named by Daniel Lindenberg, are examined here to illustrate some key theoretical questions concerning the historical processes which have led to the current crisis, and the possible directions in which France could move in the future. Neither Gauchet nor Taguieff deserves to be labelled as a reactionary in the sense implied by Lindenberg. However they have both offered sophisticated perspectives on the problems of adaptation faced by France with regard to the practice of government, the evolution of democracy, changing patterns of civic participation, and the challenge of integrating ethnic minorities, during a period when Europeanization and globalization call the role of the nation-state itself into question.
Non-conformism, `insolence' and reaction Jean Galtier-Boissière's Le Crapouillot
Authors: Hewitt Nicholas
Published: September 2007

This article explores the origins of late twentieth-century reactionary political culture through an analysis of Jean Galtier-Boissière and his magazine Le Crapouillot, founded in 1915, which finally ceased publication in 1996. Deriving from both the avant-garde of the belle époque and libertarian politics, the magazine, re-launched in 1919, played a major role in the shaping and expression of political and artistic `non-conformism' in the inter-war years. However, this `non-conformism' began to present certain reactionary characteristics which were accentuated in the immediate post-Liberation period by Le Crapouillot 's fellow-feeling with dissident right-wing political and artistic currents, with which it shared a particular tone, `insolence'. Throughout the Fourth and early Fifth Republics, until Galtier-Boissière's death in 1966, Le Crapouillot presented increasingly recognizable reactionary characteristics, culminating logically in the final phase of the magazine, when it had an explicitly right-wing, and even extreme right-wing, management. An exploration of the history of the journal, together with a discussion of the role of its founding editor, provides a useful insight into the long-term origins, both political and cultural, of late twentieth-century reactionary culture.
Research on Marketing Ethics: A Systematic Review of the Literature
Authors: Nill Alexander , Schibrowsky John A.
Published: September 2007

The growing field of marketing ethics research is investigating the many aspects of marketing that have an ethical dimension. This article provides a systematic review of this research by (1) developing a categorization scheme for marketing ethics research, and (2) by analyzing—via content analysis—all journal articles, which have been revealed by a major search engine for the time span 1981 to 2005, in terms of quantity, nature and scope, topical areas, and publication outlets. While the results indicate an increase in the number of publications, marketing ethics became less represented in the mainstream literature. Much progress has been made in areas such as improving our understanding of marketers' values, marketers' ethical decision-making processes, and cross-cultural related issues. Societal issues and basic normative questions attracted substantially less interest from researchers.
Pediatric Oncology Nurses' Attitudes Related to Discussing Fertility Preservation With Pediatric Cancer Patients and Their Families
Authors: Vadaparampil Susan T. , Clayton Heather , Quinn Gwendolyn P. , King Lindsey M. , Nieder Michael , Wilson Crystal
Published: September 2007

This study explores nurses' attitudes toward the discussion of fertility preservation (FP) with pediatric cancer patients and their families. A cross-sectional survey was administered to attendees of a pediatric oncology conference. Of the 115 nurses who responded and comprised the study sample, most reported discussing risks of infertility or FP ≤ 50% of the time. The 3 attitudinal factors most commonly rated by nurses to influence discussion of FP are the potential of upsetting patients' families, that boys younger than 18 years should not be given erotic materials during semen collection, and difficulty locating FP facilities. The 3 patient factors most likely to encourage the discussion of FP are the patient being recently married or engaged, the patient asking about FP, and availability of patient education materials. While the results indicate that nurses do not regularly discuss FP with their patients, nurses perceive such discussion as being within their scope of practice. Therefore, with appropriate intervention, nurses may play a key role in facilitating discussions regarding FP with patients and families.
Global Standards in Action: Insights from Anti-Money Laundering Regulation
Authors: Hülsse Rainer , Kerwer Dieter
Published: September 2007

As organizations have come under the increasing influence of global rules of all sorts, organization scholars have started studying the dynamics of global regulation. The purpose of this article is to identify and evaluate the contribution to this interdisciplinary field by the `Stockholm Centre for Organisational Research'. The latter's key proposition is that while global regulation often consists of voluntary best practice rules it can nevertheless become highly influential under certain conditions. We assess how innovative this approach is using as a benchmark the state of the art in another field of relevance to the study of global regulation, i.e. `International Relations'. Our discussion is primarily theoretical but we draw on the case of global anti-money laundering regulation to illustrate our arguments and for inspirations of how to further elaborate the approach.
Standard Setting and Following in Corporate Governance: An Observation-Theoretical Study of the Effectiveness of Governance Codes
Authors: Seidl David
Published: September 2007

Researchers have lately been pointing out the increasing significance of standards in all areas of contemporary life. There have been calls for more research into the processes of setting and following standards. In this article we analyse the effectiveness of codes of corporate governance as a specific type of standard that has become particularly prominent over the last decade. On the basis of an observation-theoretical approach, codes are conceptualized as schemas of observation that establish a field of mutual observations. The effectiveness of codes depends on the one hand on the extent to which they become integrated into recursive cycles of mutual observation between the corporation and the various actors in the field. On the other hand, effectiveness depends on how codes relate to other observational schemas. On the basis of the analysis several propositions about the effectiveness of code regulation are developed, which may be tested in further empirical studies.
Identification of CMS as a cytosolic adaptor of the human pTα chain involved in pre-TCR function
Authors: Navarro María N. , Nusspaumer Gretel , Fuentes Patricia , González-García Sara , Alcain Juan , Toribio María L.
Published: September 2007

The T-cell receptor β (TCRβ)/pre-TCRα (pTα) pre-TCR complex (pre-TCR) signals the expansion and differentiation of de-veloping thymocytes. Functional pro-perties of the pre-TCR rely on its unique pTα chain, which suggests the participation of specific intracellular adaptors. However, pTα-interacting molecules remain unknown. Here, we identified a polyproline-arginine sequence in the human pTα cytoplasmic tail that interacted in vitro with SH3 domains of the CIN85/CMS family of adaptors, and mediated the recruitment of multiprotein complexes involving all (CMS, CIN85, and CD2BP3) members. Supporting the physiologic relevance of this interaction, we found that 1 such adaptor, CMS, interacted in vivo with human pTα, and its expression was selectively up-regulated during human thymopoiesis in pre-TCR–activated thymocytes. Upon activation, pre-TCR clustering was induced, and CMS and polymerized actin were simultaneously recruited to the pre-TCR activation site. CMS also associated via its C-terminal region to the actin cytoskeleton in the endocytic compartment, where it colocalized with internalized pTα in traffic to lysosomal degradation. Notably, deletion of the pTα CIN85/CMS-binding motif impaired pre-TCR–mediated Ca2+ mobilization and NFAT transcriptional activity, and precluded activation induced by overexpression of a CMS-SH3 N-terminal mutant. These results provide the first molecular evidence for a pTα intracellular adaptor involved in pre-TCR function.
Uniform sensitivity of FLT3 activation loop mutants to the tyrosine kinase inhibitor midostaurin
Authors: Barry Elly V. , Clark Jennifer J. , Cools Jan , Roesel Johannes , Gilliland D. Gary
Published: September 2007

Small molecule inhibitors that target fms-like tyrosine kinase 3 (FLT3)–activating mutations have potential in the treatment of leukemias. However, certain mutations can simultaneously activate the tyrosine kinase, and confer resistance to small molecule inhibitors. We therefore tested the sensitivity of 8 FLT3 activation loop mutants to midostaurin. Each mutant conferred IL-3 factor–independent proliferation to Ba/F3 cells, and each resulted in the constitutive activation of FLT3 and its targets, signal transducer and activator of transcription 5 (STAT5) and extracellular stimuli-responsive kinase (ERK). For each mutant tested, midostaurin inhibited cell growth and phosphorylation of FLT3, STAT5, and ERK. In contrast, midostaruin did not inhibit Ba/F3 cells stably transduced with FLT3-internal tandem duplications containing a G697R mutation that confers resistance to midostaurin, demonstrating that midostaurin inhibition of FLT3 activation loop mutants was not due to off-target effects. We conclude that midostaurin is a potent inhibitor of a spectrum of FLT3 activation loop mutations, and that acute myeloid leukemia patients with such mutations are potential candidates for clinical trials involving midostaurin.
Characterization of the equine 2'-5' oligoadenylate synthetase 1 (OAS1) and ribonuclease L (RNASEL) innate immunity genes
Authors: Rios Jonathan J , Perelygin Andrey A , Long Maureen T , Lear Teri L , Zharkikh Andrey A , Brinton Margo A , Adelson David L
Published: September 2007

Background

The mammalian OAS/RNASEL pathway plays an important role in antiviral host defense. A premature stop-codon within the murine Oas1b gene results in the increased susceptibility of mice to a number of flaviviruses, including West Nile virus (WNV). Mutations in either the OAS1 or RNASEL genes may also modulate the outcome of WNV-induced disease or other viral infections in horses. Polymorphisms in the human OAS gene cluster have been previously utilized for case-control analysis of virus-induced disease in humans. No polymorphisms have yet been identified in either the equine OAS1 or RNASEL genes for use in similar case-control studies.

Results

Genomic sequence for equine OAS1 was obtained from a contig assembly generated from a shotgun subclone library of CHORI-241 BAC 100I10. Specific amplification of regions of the OAS1 gene from 13 horses of various breeds identified 33 single nucleotide polymorphisms (SNP) and two microsatellites. RNASEL cDNA sequences were determined for 8 mammals and utilized in a phylogenetic analysis. The chromosomal location of the RNASEL gene was assigned by FISH to ECA5p17-p16 using two selected CHORI-241 BAC clones. The horse genomic RNASEL sequence was assembled. Specific amplification of regions of the RNASEL gene from 13 horses identified 31 SNPs.

Conclusion

In this report, two dinucleotide microsatellites and 64 single nucleotide polymorphisms within the equine OAS1 and RNASEL genes were identified. These polymorphisms are the first to be reported for these genes and will facilitate future case-control studies of horse susceptibility to infectious diseases.
End-sequencing and characterization of silkworm (Bombyx mori) bacterial artificial chromosome libraries
Authors: Suetsugu Yoshitaka , Minami Hiroshi , Shimomura Michihiko , Sasanuma Shun-ichi , Narukawa Junko , Mita Kazuei , Yamamoto Kimiko
Published: September 2007

Background

We performed large-scale bacterial artificial chromosome (BAC) end-sequencing of two BAC libraries (an Eco RI- and a Bam HI-digested library) and conducted an in silico analysis to characterize the obtained sequence data, to make them a useful resource for genomic research on the silkworm (Bombyx mori).

Results

More than 94000 BAC end sequences (BESs), comprising more than 55 Mbp and covering about 10.4% of the silkworm genome, were sequenced. Repeat-sequence analysis with known repeat sequences indicated that the long interspersed nuclear elements (LINEs) were abundant in Bam HI BESs, whereas DNA-type elements were abundant in Eco RI BESs. Repeat-sequence analysis revealed that the abundance of LINEs might be due to a GC bias of the restriction sites and that the GC content of silkworm LINEs was higher than that of mammalian LINEs. In a BLAST-based sequence analysis of the BESs against two available whole-genome shotgun sequence data sets, more than 70% of the BESs had a BLAST hit with an identity of ≥ 99%. About 14% of Eco RI BESs and about 8% of Bam HI BESs were paired-end clones with unique sequences at both ends. Cluster analysis of the BESs clarified the proportion of BESs containing protein-coding regions.

Conclusion

As a result of this characterization, the identified BESs will be a valuable resource for genomic research on Bombyx mori, for example, as a base for construction of a BAC-based physical map. The use of multiple complementary BAC libraries constructed with different restriction enzymes also makes the BESs a more valuable genomic resource. The GenBank accession numbers of the obtained end sequences are DE283657–DE378560.
p38 Mitogen-Activated Protein Kinase Is Critical for Synergistic Induction of the FSHβ Gene by Gonadotropin-Releasing Hormone and Activin through Augmentation of c-Fos Induction and Smad Phosphorylation
Authors: Coss Djurdjica , Hand Cameron M. , Yaphockun Karen K. J. , Ely Heather A. , Mellon Pamela L.
Published: September 2007

GnRH and activin independently and synergistically activate transcription of the FSH β-subunit gene, the subunit that provides specificity and is the limiting factor in the synthesis of the mature hormone. This synergistic interaction, as determined by two-way ANOVA, is specific for FSHβ and may, therefore, contribute to differential expression of the two gonadotropin hormones, which is critical for the reproductive cycle. We find that the cross-talk between the GnRH and activin signaling pathways occurs at the level of p38 MAPK, because the synergy is dependent on p38 MAPK activity, which is activated by GnRH, and activin cotreatment augments p38 activation by GnRH. Both the Smad and activator protein-1 binding sites on the FSHβ promoter are necessary and sufficient for synergy. After cotreatment, Smad 3 proteins are more highly phosphorylated on the activin-receptor signaling-dependent residues on the C terminus than with activin treatment alone, and c-Fos is more highly expressed than with GnRH treatment alone. Inhibition of p38 by either of two different inhibitors or a dominant-negative p38 kinase abrogates synergy on FSHβ expression, reduces c-Fos induction by GnRH, and prevents the further increase in c-Fos levels that occurs with cotreatment. Additionally, p38 is necessary for maximal Smad 3 C-terminal phosphorylation by activin treatment alone and for the further increase caused by cotreatment. Thus, p38 is the pivotal signaling molecule that integrates GnRH and activin interaction on the FSHβ promoter through higher induction of c-Fos and elevated Smad phosphorylation.
High-performance n-Type Organic Field-effect Transistors Based on Co-oligomers Containing a Trifluoromethylphenylthiazolyl Group and a Biphenylene Core
Authors: Kojima Takahiro , Nishida Jun-ichi , Tokito Shizuo , Yamashita Yoshiro
Published: September 2007

New co-oligomers containing trifluoromethylphenylthiazolyl and phenylene units were prepared. The derivative with thiazolyl and biphenyl units showed high-performance n-type FET behavior.
Letter: In Situ Chemical Ionization in Ion Trap Mass Spectrometry—The Beneficial Influence of Isobutane as a Reagent Gas
Authors: Bouchonnet Stéphane , Kinani Saïd , Sablier Michel , Pirnay Stéphane
Published: September 2007

We report a comparison of the ionization yields provided by the most common reagents (methane, ammonia, methanol, acetonitrile and isobutane) performing in situ chemical ionization with an ion trap mass spectrometer. Four molecules were chosen in the medical field to illustrate experimental results: alprazolam, diazepam, flunitrazepam and acetaminophen. Under usual operational conditions, relative abundances of protonated ions appreciably depend on the reagents. The greatest abundance of MH+ ions was obtained with isobutane while observed intensities for MH+ ions varied from 73% for methanol and ammonia to about 23% for acetonitrile and methane. Results were rationalized comparing energies of formation of the reagent ions and storage efficiency in the trapping field.
Letter: Liquid Chromatography Ion-Trap Time-of-Flight Mass Spectrometric Study on the Fragmentation of an Acetildenafil Analogue
Authors: Zou Peng , Oh Sharon Sze-Yin , Kiang Kin-Har , Low Min-Yong , Koh Hwee-Ling
Published: September 2007

Liquid chromatography ion-trap time-of-flight mass spectrometry was employed to elucidate the fragmentation pathways of an analogue of acetildenafil. Based on the accurate masses of the parent ion, product ions and neutral losses of acetildenafil analogue, its fragmentation pathways were proposed. The information is useful for the on-line structural identification of unknown analogues of acetildenafil found as adulterants in herbal products.
Letter: Does the Reagent Gas Influence Collisional Activation When Performing in Situ Chemical Ionization with an Ion Trap Mass Spectrometer?
Authors: Bouchonnet Stéphane , Kinani Said , Sablier Michel
Published: September 2007

Users of ion trap mass spectrometers frequently develop methods that associate chemical ionization with tandem mass spectrometry detection. With apparatus using internal ionization, the chemical reagent is present in the trap during the collision induced dissociation (CID) step and one may wonder if the reagent influences the fragmentation ratios in MS/MS. We report a comparison of the fragmentation ratios of protonated molecules when using the most common reagents (methane, ammonia, methanol, acetonitrile, isobutane) for performing in situ chemical ionization. Four molecules were chosen in the medical field to serve as models: alprazolam, diazepam, flunitrazepam and acetaminophen. In the non-resonant CID mode, the influence of the reagent mass is clearly seen in spite of its low partial pressure in the ion trap; the reagent acts as a “heavy target”: the degree of fragmentation increases with the molecular weight of the reagent. In the resonant CID mode, there is no evident correlation between the fragmentation ratio of MH+ ions and the nature of the CI reagent; a slight shift of the secular frequency of the precursor ion, which tends to reduce the CID efficiency, could compensate for the “heavy target” effect underscored in the non-resonant mode.
Psychological Distress in International University Students: An Australian Study
Authors: Khawaja Nigar Gohar , Dempsey Jenny
Published: September 2007

Australia is a much sought-after destination of study for many thousands of international university students. However, tertiary study brings with it many challenges that may potentially precipitate psychological distress in international students. Psychological distress may be experienced in various ways. The aim of this study was to investigate the manner in which psychological distress is manifested in international students and the factors that contribute to their psychological distress. The participants consisted of 86 international students enrolled at a Queensland university who completed a battery of 9 self-report questionnaires. Results showed that obsessive–compulsiveness reflected by worry, ruminations and perfectionist tendencies was the most common symptom of psychological distress in international students. Dysfunctional coping was the only factor contributing to psychological distress. These findings have important implications for the international students with reference to the assessment of their mental health issues and the designing of suitable intervention programs.
Antecedents to Women's Fear of Rape
Authors: O'Donovan Analise , Devilly Grant J. , Rapee Ronald M.
Published: September 2007

This study assessed the relative merits of sociodemographic variables and psychological variables in understanding women's fear of rape. A comprehensive understanding of the factors involved in women's fear of rape may allow for more effective interventions with women. Four hundred and eleven women, aged 18 years or older participated in the study, which surveyed their fear of rape and experience of rape. In agreement with previous findings, sociodemographic variables contributed significantly but relatively little (13%) to the variance in women's fear of rape. In contrast, psychological factors (perceived likelihood of being raped and perceived severity of consequences) predicted an additional 29% of the variance to this fear. Greater perceived likelihood of being raped functioned as a partial mediating variable between sociodemographic factors of age and relationship status and women's fear of rape. These results are encouraging as psychological models provide more avenues for restructuring such fear and modifying concordant, dysfunctional behaviours. Consequently, these results provide direction to intervention and education programs aimed at reducing women's fear of rape.
Persistence of Obsessive Compulsive Symptoms: Similarities and Contrasts with Symptoms of Depression in a Turkish Sample
Authors: Altın Müjgan , Gençöz Tülin
Published: September 2007

Contemporary cognitive theories of obsessive-compulsive disorder (OCD) propose that certain types of dysfunctional beliefs and assumptions play a salient role in the genesis and persistence of OCD (e.g., Clark, 2004; Rachman, 1993, 1997; Salkovskis, 1985). The present study aimed to examine whether the three proposed dysfunctional beliefs — inflated sense of responsibility, thought suppression, and thought-action fusion — play a significant role particularly on the persistence of obsessive–compulsive (OC) symptoms, as compared to other emotional disorders, such as symptoms of depression. The participants of the present study were 109 undergraduate university students, who completed a set of questionnaires, including The Responsibility Attitude Scale (RAS), The Thought Action Fusion Scale (TAF), The White Bear Suppression Inventory (WBSI), The Maudsley Obsessive–Compulsive Inventory (MOCI), and The Beck Depression Inventory (BDI). After a 4-week interval, participants were again asked to complete the MOCI and BDI. Two separate hierarchical regression equations were formulated to examine the factors significantly accounting for the residual changes from Time 1 to Time 2 assessments of OC and depressive symptomatologies. Results of these analyses indicated that while thought suppression (WBSI scores) played a significant role on the persistence of both OC and depressive symptoms across time, the role of inflated sense of responsibility (RAS scores) was specific to the persistence of OC symptoms.
A Cognitive Behavioural Coaching Intervention for the Treatment of Perfectionism and Self-Handicapping in a Nonclinical Population
Authors: Kearns Hugh , Forbes Angus , Gardiner Maria
Published: September 2007

This study examined the efficacy of a modified form of cognitive behavioural therapy, known as cognitive behavioural coaching, in reducing levels of perfectionism and self-handicapping in a non-clinical population. Twenty-eight research higher degree students participated in an intensive workshop series held over 6 weeks. Perfectionism and self-handicapping were measured at the commencement and conclusion of the workshop series, and again 4 weeks later. Levels of perfectionism fell during the workshop series and this reduction was sustained at follow-up. Levels of self-handicapping did not fall during the workshop series but had fallen significantly by follow-up. Participants' level of satisfaction with their candidature progress also improved. This study demonstrates how the principles of CBT can be successfully modified and used with a nonclinical population.
Satisfaction With Pharmacy Services Among Older Adults in New Zealand
Authors: Paddison Charlotte A. M. , Pachana Nancy A.
Published: September 2007

Objectives: This study aimed to: (a) ascertain levels of satisfaction with pharmacy services, and (b) identify possible barriers to pharmacy services utilisation among older adults in New Zealand. Method: Data was collected using a mailed questionnaire. Participants were older adults randomly selected from the general electoral roll (N= 180). Results: While satisfaction with pharmacy services was found to be generally high among older adults, considerable dissatisfaction was evident in relation to the cost of medication. Conclusions: While dissatisfaction was expressed with the cost of prescriptions, at present this does not appear linked to a failure to uplift medication. Physical access to pharmacy services may be compromised by disabling health problems, particularly among those living alone.