bluuebunny/crossref_metadata_2025 huggingface dataset:
Community Blood Supply Model: Development of a New Model to Assess the Safety, Sufficiency, and Cost of the Blood Supply
Authors: Custer Brian , Johnson Eric S. , Sullivan Sean D. , Hazlet Tom K. , Ramsey Scott D. , Murphy Edward L. , Busch Michael P.
Published: September 2005

Background. Through a combination of predonation donor screening and donated unit testing, the blood supply is safer than ever. However, as a result of increasingly stringent screening measures, one of the greatest threats may be an insufficient supply. The balance between safety and adequacy of the blood supply has not received enough attention. Study Design and Methods. The authors developed a model to allow for empirical investigation of the determinants of a safe and sufficient supply. The model is a cohort simulation of allogeneic whole-blood donation, with the population of presenting donors stratified into 8 age and gender groups because the probability of donor and donation deferral varies by these characteristics. Parameters are estimated from year 2000 Blood Centers of Pacific (BCP) data. The model includes cost parameters, which were estimated using BCP expenditure data. The main outcomes are the number of transfusable units of blood and the unit cost of procurement. Results. The model tracks the production of a supply of blood, highlighting the influence of demographic characteristics, predonation deferral, underweight collection of blood units, and associated costs. The authors sought to establish model validity by showing that modeled results closely mimic the outcomes and costs observed by blood bank administrators. Conclusion. The model was developed to evaluate blood safety and policy decisions; it can be used to assess the impact of predonation deferrals, such as expanded European travel deferral for variant Creutzfeldt-Jakob disease, or the impact of new testing strategies, such as nucleic acid testing for West Nile virus.
Assessing the Cost-Effectiveness of New Pharmaceuticals in Epilepsy in Adults: The Results of a Probabilistic Decision Model
Authors: Hawkins Neil , Epstein David , Drummond Michael , Wilby Jennifer , Kainth Anita , Chadwick David , Sculpher Mark
Published: September 2005

Epilepsy currently affects more than 400,000 people in the United Kingdom and 2.3 million in the United States. Drug therapy is the mainstay of treatment for patients with epilepsy, but therapies vary widely in their mechanism of action and acquisition cost. This article describes a decision model developed for the National Institute for Clinical Excellence in the United Kingdom. It compares the long-term cost-effectiveness of drugs licensed in adults for use in 3 situations: monotherapy for newly diagnosed patients, monotherapy for refractory patients, and combination therapy for refractory patients. The analysis separately considers the treatment of partial and generalized seizures. The full range of pharmaceutical therapies feasibly used in the UK health system was included in the analysis. The analysis showed that, on the basis of existing evidence, for newly diagnosed patients with partial seizures, carbamazepine and valproate are likely to be the most cost-effective mono-therapies. Carbamazepine is likely to be the most cost-effective 2nd-line monotherapy for refractory patients, and oxcarbazepine would probably be the most cost-effective adjunctive therapy for refractory patients if the willingness to pay for additional health benefits is greater than £18,000 per quality-adjusted life year (QALY). For patients with generalized seizures, valproate is most likely to be cost-effective for newly diagnosed patients. For refractory patients, adjunctive topiramate is more cost-effective than monotherapy alone if the willingness to pay for additional health benefits is greater than £35,000 per QALY. There is, however, considerable uncertainty regarding these results. Some of the methodological features of the study will be of value in designing cost-effectiveness analyses of other therapies for chronic conditions. These include the methods used to deal with the absence of head-to-head trial data and the need to reflect time dependency in Markov transition probabilities.
Analytic Choices in Economic Models of Treatments for Rheumatoid Arthritis: What Makes a Difference?
Authors: Drummond M. F. , Barbieri M. , Wong J. B.
Published: September 2005

Objectives. To compare the analytic judgments, data, and assumptions of different models used in the economic evaluation of infliximab, one of a new class of drugs for rheumatoid arthritis (RA). Methods. A detailed assessment was made of 4 models, 1 submitted (in a reimbursement dossier) by the manufacturer, 1 produced by an independent academic group, and 2 recently published in the literature. Factors considered included the key data inputs, assumptions about the sequencing of treatments for RA, the methods used to calculate health utilities, and the estimation of cost offsets. Results. Two of the 4 models, although embodying different methodological approaches, gave fairly similar results (approximately £25,000–£35,000 cost per additional quality-adjusted life year [QALY] gained). The other 2 models, both by an independent academic group, gave much higher estimates, ranging from £50,000 to £60,000 to more than £100,000 per additional QALY. The differences appeared to depend mainly on differences in model structure, the assumptions about the positioning of infliximab in the treatment sequence, and the relationship between Health Assessment Questionnaire (HAQ) states and QALYs. Conclusions. Economic models of treatments for RA incorporate different key data inputs and analytic judgments. However, convergence was observed in some of the estimates produced by the models, particularly when adjustments were made for some of the differences in input parameters. Nevertheless, differences in the choice of model structure and in key assumptions also had a major impact on results. Therefore, more discussion is needed to reach a consensus on some of these methodological issues.
Cost-Effectiveness Analysis of Treatments for Chronic Disease: Using R to Incorporate Time Dependency of Treatment Response
Authors: Hawkins Neil , Sculpher Mark , Epstein David
Published: September 2005

When constructing decision-analytic models to evaluate the cost-effectiveness of alternative treatments, we often need to extrapolate beyond the available experimental data, as these typically relate to a limited period starting from the initiation of a new treatment or the diagnosis of the current disease state. We may also be required to extrapolate beyond the available experimental evidence to compare potential treatment sequences. Markov models are often used for this extrapolation. These models have the defining assumption that future transition probabilities are independent of past transitions. This means that, in general, transition probabilities cannot be conditional of the time spent in a given state. Where data exist to show that the risks of transition are conditional on the time spent in the treatment state, the simplifying Markov assumption can result in a loss in the model’s “face validity,” and misleading results might be generated. Several methods are available to incorporate time dependency into transition probabilities based on standard methods and software. These include the inclusion of tunnel states in Markov models and patient-level simulation, where a series of individual patients are simulated. This article considers the features and limitations of these methods and also describes a novel approach to building time dependency into a Markov model by incorporating an additional time dimension resulting in a “semi-Markov” model. An example of the implementation of such a model, using the R statistical programming language, is illustrated using a cost-effectiveness model for new epilepsy therapies.
We’ve Had Training, Now What?
Authors: Minsky-Kelly Debbie , Hamberger L. Kevin , Pape Deborah A. , Wolff Marie
Published: September 2005

The present study assesses barriers to identification and referral of domestic violence (DV) victims by staff at a health care institution following a 3-hr DV training program in which 752 health care providers participated. Focus groups are conducted with staff in hospital departments that serve a high volume of women. Responses to focus group questions identify system-wide and individual hospital department barriers. These barriers have implications for health care organizations trying to implement DV screening protocols through training alone to change staff behavior in diverse clinical settings. Limitations of this study and future research recommendations are also discussed.
The Changing Pension Landscape
Authors: Morris Jim
Published: September 2005

The landscape facing corporate pension plan sponsors has changed dramatically over the past five years. Quite possibly, the most significant risk facing corporate plan sponsors is the refusal to acknowledge that the pension environment is fundamentally different. Today, pension managers are looking for answers to a new set of problems brought to light by the fact that these corporate plans now represent a material portion of the corporate balance sheet and are often now operating with a financial deficit. Although the problem is now apparent, the solutions typically are not. Most pension managers when faced with the new challenges have the tendency to go to the same old well for answers. Unfortunately, they are likely to find the same solutions—ones that only worked in earlier days. For the executive in charge of managing this benefit, the solution is a more integrated approach that seeks to align all components of the plan with corporate strategies across the entire organization. Aligning all aspects of plan management will help optimize the well-being and performance of the plan and the organization.
Short-Term Redemption Fees Burden 401(k) Plans
Authors: Hamilton Thad D.
Published: September 2005

Some mutual fund companies are imposing short-term redemption fees that are curtailing investment activity in 401(k) plans. Although average 401(k) plan balances are low and participants as investors in these plans are generally are in it for the long term, the short-term redemption fees are affecting the ways employers as plan sponsors manage their plans. The fees don’t come in response to any activity that was taking place at the 401(k) participant level but rather were established to curtail questionable trading activities conducted by large-scale investors. Whereas the vast majority of the damage caused by the inappropriate or illegal mutual fund trading was caused by hedge funds or large professionally managed asset pools, imposing restrictions to curtail these investors is impacting trading at the participant level in 401(k) plans.
Evaluating Human Resource Pay and Reward Computer and Web Products
Authors: Zingheim Patricia K. , Schuster Jay R.
Published: September 2005

New technology products for compensation vary widely in their substance, utility, and long-term value. Buyers need to review and consider these tools based on the company’s specific needs and whether they provide better pay management or just accelerate a pay system that needs revision beyond automation.
Vernacular Security: The Politics of Feeling Safe in Global, National and Local Worlds
Authors: Bubandt Nils
Published: September 2005

Tracing the political history of the concept of ‘security’ through a variety of global, national and regional inflections, this article argues for the analytical usefulness of the concept of ‘vernacular security’. Entailed by this concept is a proposal to treat ‘security’ as a socially situated and discursively defined practice open to comparison and politically contextualized explication, rather than merely an analytical category that needs refined definition and consistent use. While the ideas and politics of security associated with the rise of global governance are built on late-modern ideas about what it means to be safe, global governance is not seamless in its extension. The apparent universalism of the ontology and politics of global security therefore breaks down into a more complex pattern upon closer inspection. Based on material from Indonesia, the article suggests that the ‘onto-politics’ of security have global, national and local inflections, the interplay of which requires re-examination.
Addressing Ethnic Divisions in Post-Conflict Institution-Building: Lessons from Recent Cases
Authors: Simonsen Sven Gunnar
Published: September 2005

Where the lines of an armed conflict coincide with ethnic boundaries, the political salience of ethnicity increases. In post-conflict situations that may seem defined by ‘ancient hatreds’, the political salience and character of ethnic identities remain dynamic. Bringing together contributions from the comparative politics literature on power-sharing and the policy-dominated field of post-conflict peacebuilding, this article examines how ethnic divisions have been addressed in recent cases of institution-building directed by international forces following military intervention - in Bosnia, Kosovo, Afghanistan, and Iraq. It finds that an ‘assumption of intransigence’ has often influenced decisions on institutional design, and that the institutionalization of ethnicity has become an important hindrance to peacebuilding. Against this background, the article argues in favor of institutional designs that do not fixate the accentuation on ethnicity in politics: more flexible ways should be sought to assure inclusivity and representativeness for different ethnic groups. There exists a wide range of institutional-design options that can be combined, on the basis of in-depth assessments of each individual conflict, to de-ethnicize politics and build sustainable peace.
Stratification Patterns of Active Sport Involvement Among Adults
Authors: Scheerder Jeroen , Vanreusel Bart , Taks Marijke
Published: September 2005

This study examines leisure-time sport participation among adults according to their socio-cultural background and from a time-trend perspective. Using stapled cross-sectional survey data, sport participation trends in Flanders (Belgium) are studied for the 1979-99 period. The study explores the extent to which social inequalities in leisure-time sport still prevail. The results indicate that age, gender and social class remain the most important factors influencing sport involvement. Differences according to age, gender and social class are not only found with respect to participation rates; even among sport participants, social differentiation takes place in terms of the organizational context and participation preferences. Using logistic regression modelling and canonical correlation analysis, stratification patterns and different sporting styles are identified in terms of activities. The findings are discussed in terms of three decades of the Sport for All movement in Flanders.
‘Doctors Just Say “Rest and Take Ibuprofen”’
Authors: Pike Elizabeth C. J.
Published: September 2005

While sociologists have confirmed that athletes normalize illness and injury, there remains limited research into the practices of sports medicine. A two-year ethnographic study of female rowers shows that medical support for these athletes was both insufficient and inadequate. The rowers experienced a lack of medical care, and several had stories to tell of incompetent diagnoses and over-reliance on drug prescription. Many of the women turned to non-orthodox health care, which has been considered more ‘feminine’ than orthodox practices, and also empowering in terms of the active involvement of the client in the treatment process. This article critically evaluates the extent to which non-orthodox care is an authentic ‘alternative’ to traditional medical approaches, and the contention that such treatment facilitates the continued presentation of self as both ‘athlete’ and ‘female’ at a time when these identities are challenged by the injury or illness experience.
Sport in Namibia
Authors: Chappell Robert
Published: September 2005

In 2003 Namibia reached the final stages of the International Cricket Council (ICC) World Cup in South Africa, and the International Rugby Board (IRB) World Cup in Australia - a remarkable achievement for a country with a population of only 1.9 million people. This study addresses the current socio-political situation in Namibia, Africa in relation to the organization of sport. The article is based on two research visits to Namibia in which interviews were conducted with key providers of sport in Namibia. The results show that Namibia has made great strides in the administration and organization of sport since independence in 1990, and give a sense of the struggles and barriers involved in sport development in a newly independent developing nation.
Spatial Strategies and Territoriality in the Maine Lobster Industry
Authors: Acheson James M. , Gardner Roy J.
Published: September 2005

Although territoriality of one kind or another is found in every society, our understanding of the way territorial systems come into being remains undeveloped. In this article, we use game theory to understand the evolution of institutional arrangements in the Maine lobster fishery. Nash equilibrium of models explains the three stages observed in the local-scale informal system of the past century. These stages are the result of decisions to invade or defend territorial lines that have changed over the course of time in response to a number of factors, including adoption of better technology, transportation costs, ecological changes, ability to organize defensive and offensive groups, and better law enforcement - all captured by crucial parameters of our model. We explore the broader implications of this industry study, especially the issues it raises for rational choice theory and the generation of institutions and norms.
The Role of Consumers in Innovation Processes in Markets
Authors: Saam Nicole J.
Published: September 2005

What is the effect of the fallible knowledge of consumers on knowledge accumulation in markets? This is the question which this article investigates based on Hayek’s evolutionary concept of competition as a discovery procedure and of Popper’s concept of fallible knowledge. The article presents results from a simulation model. It tests the hypothesis that the growth rate of knowledge accumulation of an industry should decrease with the increase in fallible knowledge of consumers. Surprisingly, under certain conditions, the growth rate of knowledge accumulation of an industry increases with the increase in fallible knowledge of consumers.
Hacking the body: code, performance and corporeality
Authors: Thomas Douglas
Published: September 2005

This article argues for a politics of code grounded in the performance of hacking as an activity that is able to deconstruct the longstanding binary of code and performance by centering on the relationship of each to the body. Through a reading of hacker responses to the state’s restriction on the export of cryptography, the article argues that interventions by hackers reveal to us the point at which the body becomes, literally, the limit of code, marking it as irreducibly transgressive, while rendering code impotent. It is this performance, it contends, that holds the most powerful possibility for hacktivism and resistance.
Cultural differentiation or social segregation? Four approaches to the digital divide
Authors: Sassi Sinikka
Published: September 2005

This article analyses some of the contradictions of contemporary technological society through the term ‘digital divide’ and the societal consequences predicted by this development. It briefly examines the history of communication technology in the 1970s, when a lively debate about the new information and communication order and the unbalanced diffusion of mass media took place. The many views on the ‘digital divide’ are presented here as four distinct approaches differing from each other in context and definition: the technocratic approach; the social structure approach; the information structure and exclusion approach; and modernization and capitalism. The main characteristics of these discourses are explained and evaluated. The role of the information technologies in contemporary societies is briefly discussed and a tentative conclusion drawn on the issue of cultural differentiation as against social segregation in a context of a technologically advanced Nordic country. In conclusion, a few ideas concerning the adoption and use of the internet in a given locality are given.
ZAP-70 expression in acute lymphoblastic leukemia: association with the E2A/PBX1 rearrangement and the pre-B stage of differentiation and prognostic implications
Authors: Chiaretti Sabina , Guarini Anna , De Propris Maria Stefania , Tavolaro Simona , Intoppa Stefania , Vitale Antonella , Iacobelli Simona , Elia Loredana , Ariola Cristina , Ritz Jerome , Foà Robin
Published: September 2005

We evaluated the expression of 2 members of the Syk family, ZAP-70 and Syk, in acute lymphoblastic leukemia (ALL) samples, using data derived from a series of 33 T-ALL and 95 B-lineage adult ALL patients analyzed by oligonucleotide arrays. Of the B-lineage ALL cases, 37 were BCR/ABL+, 10 were ALL1/AF4+, 5 were E2A/PBX1+, and 43 carried no known molecular abnormality. ZAP-70 was highly expressed in T-ALL. A high ZAP-70 expression was also found in a proportion of B-lineage ALL, the highest levels being associated with the E2A/PBX1+ group and the lowest with ALL1/AF4+ cases (P < .001). A higher ZAP-70 expression was also observed in the pre-B group (P < .001). Remarkably, Syk expression was always preserved, suggesting that ZAP-70 expression is not substitutive of Syk. At the protein level, ZAP-70 was evaluated on 39 newly diagnosed ALL patients (25 adults, 14 children) and was detected in 23 cases (59%). ZAP-70 expression was consistently found in Igμ+ cases. Evaluation of long-term outcome in cases without molecular abnormalities showed that the higher levels of ZAP-70 were coupled to a higher relapse rate. In ALL, ZAP-70 expression is associated with the E2A/PBX1 rearrangement and pre-B stage and may have a prognostic role and be a candidate molecule for targeted therapies.
FGF-2 binding to fibrin(ogen) is required for augmented angiogenesis
Authors: Sahni Abha , Khorana Alok A. , Baggs Raymond B. , Peng Hu , Francis Charles W.
Published: September 2005

We have shown previously that fibrin(ogen) binds fibroblast growth factor 2 (FGF-2) and potentiates stimulation of endothelial-cell (EC) proliferation. We have now used 2 FGF-2 mutants differing only in the 5 residues constituting the binding site to characterize the importance of this interaction in angiogenesis. The nonbinding (2212) and binding (221*2) mutants stimulated EC proliferation by 2.2 ± 0.4-fold and 2.9 ± 0.3-fold over control, respectively, and both were similar to wild-type (wt) FGF-2 (2.5 ± 0.3-fold). Proliferation was augmented by fibrinogen to 5.3 ± 1.2-fold and 4.8 ± 0.8-fold with wtFGF-2 and 221*2, whereas no augmentation occurred with 2212 and fibrinogen. Using a placental explant model in a fibrin matrix, wtFGF-2 resulted in 2.6 ± 0.9-fold more growth over control, and 221*2 increased growth 3.3 plus or minus 0.9-fold. Vessel outgrowth with 2212 was minimal and comparable to control. Similarly, fibrinogen potentiated wtFGF-2 or 221*2-mediated angiogenesis in the chicken chorioallantoic membrane model. In a mouse Matrigel implant model, fibrinogen significantly increased angiogenesis with either wtFGF-2 or 221*2, whereas there was no augmentation with 2212. These results demonstrate that binding of FGF-2 to fibrin(ogen) mediated by the 5-residue FGF-2-fibrin(ogen) interactive site is required for augmented angiogenesis.
Modulation of ADAMTS13 secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation
Authors: Plaimauer Barbara , Fuhrmann Jakob , Mohr Gabriele , Wernhart Waltraud , Bruno Katharina , Ferrari Silvia , Konetschny Christian , Antoine Gerhard , Rieger Manfred , Scheiflinger Friedrich
Published: September 2005

Sequence analysis of the ADAMTS13 locus of 2 patients with hereditary thrombotic thrombocytopenic purpura (TTP) revealed the homozygous presence of 4 single nucleotide polymorphisms (SNPs) (R7W, Q448E, P618A, A732V) and a rare missense mutation (R1336W). Analysis of the individual effect of any amino acid exchanges showed that several sequence variations can interact with each other, thereby altering the phenotype of ADAMTS13 deficiency. Introduction of polymorphisms R7W, Q448E, and A732V had no or only minor effects on ADAMTS13 secretion. In contrast, P618A, R1336W, and the A732V-P618A combination strongly reduced ADAMTS13-specific activity and antigen levels. Surprisingly, R7W and Q448E were positive modifiers of ADAMTS13 secretion in the context of P618A and A732V but neither could rescue the severely reduced specific activity conferred by P618A. However, in the context of R1336W, polymorphisms R7W and Q448E enhanced the detrimental effect of the missense mutation and led to undetectable enzyme activity. We show that dependent on the sequence context, the same polymorphisms might be either positive or negative modifiers of gene expression. Our results might therefore be widely relevant to understanding the influence of polymorphisms on the phenotypic expression of complex diseases.
Initial depletion of regulatory T cells: the missing solution to preserve the immune functions of T lymphocytes designed for cell therapy
Authors: Mesel-Lemoine Mariana , Cherai Mustapha , Le Gouvello Sabine , Guillot Maude , Leclercq Virginie , Klatzmann David , Thomas-Vaslin Véronique , Lemoine François M.
Published: September 2005

We investigated the causes of the altered functionality of T cells cultured under conditions designed for cell and gene therapy and the strategies to prevent their defects. We first showed that human T cells cultured for 6 days with anti-CD3 ± anti-CD28 antibodies and interleukin-2 presented a 50% decrease of their proliferative responses to allogeneic or recall antigens. Similarly, day-6 cultured murine T cells completely lost their capacity to reject allogeneic skin grafts and to provoke graft-versus-host disease (GVHD) when infused into irradiated semi-allogeneic mice. Interestingly, injection of higher amounts of cultured T cells restored GVHD induction. Moreover, depletion of CD25+ cells prior to T-cell cultures can prevent these deficiencies both in mice and humans. Therefore, we demonstrated that culture conditions used for T-cell therapy preferentially activated and expanded regulatory T cells (Treg's). Thus, we showed that dividing cells sorted from T-cell cultures strongly suppressed the proliferation of autologous T cells in response to allogeneic stimulation. An increased detection of Foxp3 at mRNA and protein levels in the cultures confirmed the Treg expansion. Overall, we demonstrate that T-cell cultures promote Treg expansion over effector T cells, leading to deleterious immune functions, and that this imbalance can be prevented by an initial depletion of CD25+ cells.
Loss of Sp1 function via inhibitory phosphorylation in antifolate-resistant human leukemia cells with down-regulation of the reduced folate carrier
Authors: Stark Michal , Assaraf Yehuda G.
Published: September 2005

The reduced folate carrier (RFC) is the dominant influx transporter for antifolates. A major mechanism of antifolate resistance is loss of RFC (SLC19A1) gene expression due to decreased GC-box-dependent transcription. However, despite the poor GC-box binding in multiple antifolate-resistant cell lines, normal Sp1 levels were retained. Here we explored the post-translational modifications that may disrupt Sp1 function. Phospho-affinity purification of nuclear proteins revealed that resistant cells contained approximately 8-fold more phosphorylated Sp1 than parental cells; treatment of nuclear proteins from these cells with alkaline phosphatase restored GC-box binding. As protein kinase A phosphorylates Sp1, resistant cells were treated with various cAMP-reactive agents, revealing no apparent effect on GC-box binding except for the general phosphodiesterase inhibitor IBMX. As cGMP levels also may be affected by IBMX, resistant cells were treated with 8-pCPT-cGMP, resulting in the complete restoration of GC-box binding, luciferase reporter activity, and RFC mRNA levels. This restoration was abolished in the presence of the protein phosphatase 2A inhibitor (PP2A) okadaic acid. Importantly, whereas resistant cells showed multiple phosphorylated Sp1 forms barely detectable in parental cells, treatment with 8-pCPT-cGMP resulted in their elimination; this disappearance, however, was prevented by the copresence of okadaic acid. These findings provide the first evidence that loss of RFC gene expression in antifolate-resistant cells is associated with an inhibitory Sp1 phosphorylation that can be eliminated by a cGMP-dependent activation of PP2A. (Blood. 2006;107:708-715)
Laterally transferred elements and high pressure adaptation in Photobacterium profundum strains
Authors: Campanaro Stefano , Vezzi Alessandro , Vitulo Nicola , Lauro Federico M , D'Angelo Michela , Simonato Francesca , Cestaro Alessandro , Malacrida Giorgio , Bertoloni Giulio , Valle Giorgio , Bartlett Douglas H
Published: September 2005

Background

Oceans cover approximately 70% of the Earth's surface with an average depth of 3800 m and a pressure of 38 MPa, thus a large part of the biosphere is occupied by high pressure environments. Piezophilic (pressure-loving) organisms are adapted to deep-sea life and grow optimally at pressures higher than 0.1 MPa. To better understand high pressure adaptation from a genomic point of view three different Photobacterium profundum strains were compared. Using the sequenced piezophile P. profundum strain SS9 as a reference, microarray technology was used to identify the genomic regions missing in two other strains: a pressure adapted strain (named DSJ4) and a pressure-sensitive strain (named 3TCK). Finally, the transcriptome of SS9 grown under different pressure (28 MPa; 45 MPa) and temperature (4°C; 16°C) conditions was analyzed taking into consideration the differentially expressed genes belonging to the flexible gene pool.

Results

These studies indicated the presence of a large flexible gene pool in SS9 characterized by various horizontally acquired elements. This was verified by extensive analysis of GC content, codon usage and genomic signature of the SS9 genome. 171 open reading frames (ORFs) were found to be specifically absent or highly divergent in the piezosensitive strain, but present in the two piezophilic strains. Among these genes, six were found to also be up-regulated by high pressure.

Conclusion

These data provide information on horizontal gene flow in the deep sea, provide additional details of P. profundum genome expression patterns and suggest genes which could perform critical functions for abyssal survival, including perhaps high pressure growth.
Comparative analyses of six solanaceous transcriptomes reveal a high degree of sequence conservation and species-specific transcripts
Authors: Rensink Willem Albert , Lee Yuandan , Liu Jia , Iobst Stacy , Ouyang Shu , Buell C Robin
Published: September 2005

Background

The Solanaceae is a family of closely related species with diverse phenotypes that have been exploited for agronomic purposes. Previous studies involving a small number of genes suggested sequence conservation across the Solanaceae. The availability of large collections of Expressed Sequence Tags (ESTs) for the Solanaceae now provides the opportunity to assess sequence conservation and divergence on a genomic scale.

Results

All available ESTs and Expressed Transcripts (ETs), 449,224 sequences for six Solanaceae species (potato, tomato, pepper, petunia, tobacco and Nicotiana benthamiana), were clustered and assembled into gene indices. Examination of gene ontologies revealed that the transcripts within the gene indices encode a similar suite of biological processes. Although the ESTs and ETs were derived from a variety of tissues, 55–81% of the sequences had significant similarity at the nucleotide level with sequences among the six species. Putative orthologs could be identified for 28–58% of the sequences. This high degree of sequence conservation was supported by expression profiling using heterologous hybridizations to potato cDNA arrays that showed similar expression patterns in mature leaves for all six solanaceous species. 16–19% of the transcripts within the six Solanaceae gene indices did not have matches among Solanaceae, Arabidopsis, rice or 21 other plant gene indices.

Conclusion

Results from this genome scale analysis confirmed a high level of sequence conservation at the nucleotide level of the coding sequence among Solanaceae. Additionally, the results indicated that part of the Solanaceae transcriptome is likely to be unique for each species.
Modeling repeated ordinal responses using a family of power transformations: application to neonatal hypothermia data
Authors: Zayeri Farid , Kazemnejad Anoshirvan , Khanafshar Navid , Nayeri Fatemeh
Published: September 2005

Background

For analyzing a repeated ordinal response, it is common to use a multivariate cumulative logit model. This model may fit poorly, especially when a nonsymmetric response is available. In these cases, alternative strategies should be utilized.

Methods

In this paper, we present a family of power transformations for the cumulative probabilities to model asymmetric departures from the random-intercept cumulative logit model. To illustrate this method, we analyze the data from an epidemiologic study to identify risk factors of hypothermia among newly born infants in some referral university hospitals in Tehran, Iran.

Results

For hypothermia data, using this family of transformations and comparing the goodness-of-fit statistics showed that a model with the cumulative complementary log-log link gives us a better fit compared to a model with the cumulative logit link.

Conclusion

In some areas, using the ordinary cumulative logit link function does not lead to the best fit. So, other link functions should be evaluated to discover the best transformation for the cumulative probabilities.
Avoidance as a strategy of (not) coping: qualitative interviews with carers of Huntington's Disease patients
Authors: Lowit Alison , van Teijlingen Edwin R
Published: September 2005

Background

Since Huntington's Disease (HD) is a familial disease with an average onset in the mid-thirties, one might expect that spousal carers are concerned with providing care for off-spring who may turn out to be affected.

Methods

This study involved ten face-to-face interviews with carers of spouses affected by HD in Northeast Scotland. Carers were recruited through two channels: a genetic clinic and the Scottish Huntington's Association (SHA). Interviews were conducted in carers' own homes. A thematic analysis of the transcripts was conducted.

Results

Although carers did worry about their children, they did not envisage being involved in their care. Many avoided talking about the disease, both within and outwith their family; this may have greatly reduced the level of support provided by family members. Conversely, avoidance was often accompanied by symptom-spotting. For example, several people had given up driving, before they were incapable of doing so. The explanation appears to be that they avoided getting into situations in which HD may express itself.

Support meetings seem to be valued amongst patients with other serious diseases and their carers, however, although all participants had had contact with the SHA, only one regularly attended meetings. It was felt that seeing others with HD provided a constant reminder of the possible effect of HD on the wider family, which seemed to outweigh the benefit of attending. Overall, the analysis highlighted 'avoidance' as a key theme.

Conclusion

Many denied symptoms of HD in their spouses, pre-diagnosis. All had pretended at some point that it was not happening, through ignoring early signs and 'obvious' symptoms. Some partners had refused to go to the doctor until it was no longer possible to deny symptoms. Formal health and social care seemed to play a very small role compared to informal care arrangements.
Primary angiitis of the central nervous system presenting with subacute and fatal course of disease: a case report
Authors: Lukas Carsten , Keyvani Kathy , Börnke Christian
Published: September 2005

Background

Primary angiitis of the central nervous system is an idiopathic disorder characterized by vasculitis within the dural confines. The clinical presentation shows a wide variation and the course and the duration of disease are heterogeneous. This rare but treatable disease provides a diagnostic challenge owing to the lack of pathognomonic tests and the necessity of a histological confirmation.

Case presentation

A 28-year-old patient presenting with headache and fluctuating signs of encephalopathy was treated on the assumption of viral meningoencephalitis. The course of the disease led to his death 10 days after hospital admission. Postmortem examination revealed primary angiitis of the central nervous system.

Conclusion

Primary angiitis of the central nervous system should always be taken into consideration when suspected infectious inflammation of the central nervous system does not respond to treatment adequately. In order to confirm the diagnosis with the consequence of a modified therapy angiography and combined leptomeningeal and brain biopsy should be considered immediately.
AIDS knowledge and attitudes in a Turkish population: an epidemiological study
Authors: Ayranci Unal
Published: September 2005

Background

The aim of this study was to investigate and present some pertinent comments concerning Acquired Immunodeficiency Syndrome (AIDS) knowledge, attitudes and misconceptions among the general population in a city of west Turkey. This study was deemed important and relevant due to the increasing importance of AIDS in Turkey and the other countries.

Methods

Using a multistage area sampling method, a random sample of individuals aged 11–83 years, living in 65 different quarters in the city of Eskisehir, Turkey during September, October and November 2004 were interviewed.

Results

In all, 1048 respondents completed the survey. In most items, respondents displayed a fairly good to excellent degree of knowledge about HIV/AIDS. Individuals with higher degrees of education indicated more correct responses in all items relating to knowledge of HIV/AIDS.

In general, the respondents' attitudes towards AIDS and people with AIDS were found to be tolerant and positive, with one answer choice showing that the majority of the respondents agreed with the statement that those with HIV/AIDS must be supported, treated and helped (90.7%). Moreover, the proportions of the respondents' misconceptions were found to be significantly low for all the items. However, nearly one fourth of the respondents agreed with the misconceptions 'AIDS is a punishment by God' and 'One is not infected with HIV/AIDS if engaged in sport and well nourished'.

Conclusion

In general HIV/AIDS related knowledge was high and people showed positive attitudes. However, people continue to hold misconceptions about AIDS and these need to be addressed by health education programs targeting those at higher risk.
Non-obstructive azoospermia and maturation arrest with complex translocation 46,XY t(9;13;14)(p22;q21.2;p13) is consistent with the Luciani-Guo hypothesis of latent aberrant autosomal regions and infertility
Authors: Sills Eric Scott , Kim Joseph Jinsuk , Witt Michael A , Palermo Gianpiero D
Published: September 2005

Objective

To describe clinical and histological features observed in the setting of an unusual complex translocation involving three autosomes (9, 13, and 14) identified in an otherwise healthy male referred for infertility consultation.

Materials and methods

The patient was age 30 and no family history was available (adopted). Total azoospermia was confirmed on multiple semen analyses. Peripheral karyotype showed a 46,XY t(9;13;14)(p22:q21.2;p13) genotype; no Y-chromosome microdeletions were identified. Cystic fibrosis screening was negative. Bilateral testis biopsy revealed uniform maturation arrest and peritubular fibrosis.

Results

Formal genetic counseling was obtained and the extant literature reviewed with the couple. Given the low probability of obtaining sperm on testicular biopsy, as well as the high risk of any retrieved sperm having an unbalanced genetic rearrangement, the couple elected to proceed with fertility treatment using anonymous donor sperm for insemination.

Conclusion

Although genes mapped to the Y-chromosome have been established as critical to normal testicular development and spermatogenesis, certain autosomal genes are now also recognized as important in these processes. Here we present clinical evidence to support the Luciani-Guo hypothesis (first advanced in 1984 and refined in 2002), which predicts severe spermatogenic impairment with aberrations involving chromosomes 9, 13, and/or 14, independent of Y-chromosome status. Additional study including fluorescent in situ hybridization and molecular analysis of specific chromosomal regions is needed to characterize more fully the contribution(s) of these autosomes to male testicular development and spermatogenesis.
Platypnea-orthodeoxia associated with a fenestrated atrial septal aneurysm: Case Report
Authors: van Gaal William J , Joseph Majo , Jones Elizabeth , Matalanis George , Horrigan Mark
Published: September 2005

Background

Platypnea-orthodeoxia describes the condition of combined dyspnea and hypoxia respectively, whilst in the upright position, which improves in the recumbent position.

Case Report

We present a case of platypnea-orthodeoxia due to a fenestrated atrial septal defect associated with an atrial septal aneurysm. Due to the fenestrated nature of the atrial septal defect, surgical rather than percutaneous correction was performed.

Conclusion

A high index of suspicion is required to diagnose the syndrome of platypnea-orthodeoxia. Careful echocardiographic evaluation is required to identify the syndrome, and to determine suitability for percutaneous repair.
Gender differences in perceived environmental correlates of physical activity
Authors: Bengoechea Enrique Garcia , Spence John C , McGannon Kerry R
Published: September 2005

Background

Limited research has been conducted on gender differences in perceived environmental correlates of physical activity (PA). The purpose of this study was to explore the potential role of gender in the link between perceived environment and PA.

Methods

Using a telephone-administered survey, data was collected on leisure time physical activity (LTPA), perceptions of the neighbourhood environment, and self-efficacy in a representative sample of 1209 adults from the province of Alberta, Canada. LTPA was regressed on ten measures of perceived neighbourhood environment and self-efficacy in a series of logistic regressions.

Results

Women were more likely than men to perceive their neighbourhood as unsafe to go for walks at night (χ2= 67.46, p < 0.001) and to report seeing people being active in their neighbourhood (χ2= 6.73, p < 0.01). Conversely, women were less likely to perceive easy access to places for PA (χ2= 11.50, p < 0.01) and availability of places to buy things within easy walking distance from home (χ2= 4.30, p < 0.05). Adjusting for age, education, income, and place of residence, access to places for PA (OR = 2.49) and interesting things to look at in the neighbourhood (OR = 1.94), were associated with higher levels of LTPA in men. Access to places for PA (OR = 2.63) and reporting seeing people being active (OR = 1.50) were associated with increased LTPA among women. After controlling for sociodemographic variables and self-efficacy, the presence of shops and places to buy things within easy walking distance from home (OR = 1.73), interesting things to look at in the neighbourhood (OR = 1.65), and access to places for PA (OR = 1.82) were associated with higher levels of LTPA in men. Among women, no significant relationships were observed between perceived environment and LTPA after adjusting for self-efficacy.

Conclusion

The results provide additional support for the use of models in which gender is treated as a potential moderator of the link between the perceived environment and PA. Further, the results suggest the possibility of differential interventions to increase PA based on factors associated with gender.
Feedback activation of phospholipase C via intracellular mobilization and store-operated influx of Ca2+ in insulin-secreting β-cells
Authors: Thore Sophia , Dyachok Oleg , Gylfe Erik , Tengholm Anders
Published: September 2005

Phospholipase C (PLC) regulates various cellular processes by catalyzing the formation of inositol-1,4,5-trisphosphate (IP3) and diacylglycerol from phosphatidylinositol-4,5-bisphosphate (PIP2). Here, we have investigated the influence of Ca2+ on receptor-triggered PLC activity in individual insulin-secreting β-cells. Evanescent wave microscopy was used to record PLC activity using green fluorescent protein (GFP)-tagged PIP2/IP3-binding pleckstrin homology domain from PLCδ1, and the cytoplasmic Ca2+ concentration ([Ca2+]i) was simultaneously measured using the indicator Fura Red. Stimulation of MIN6 β-cells with the muscarinic-receptor agonist carbachol induced rapid and sustained PLC activation. By contrast, only transient activation was observed after stimulation in the absence of extracellular Ca2+ or in the presence of the non-selective Ca2+ channel inhibitor La3+. The Ca2+-dependent sustained phase of PLC activity did not require voltage-gated Ca2+ influx, as hyperpolarization with diazoxide or direct Ca2+ channel blockade with nifedipine had no effect. Instead, the sustained PLC activity was markedly suppressed by the store-operated channel inhibitors 2-APB and SKF96365. Depletion of intracellular Ca2+ stores with the sarco(endo)plasmic reticulum Ca2+-ATPase inhibitors thapsigargin or cyclopiazonic acid abolished Ca2+ mobilization in response to carbachol, and strongly suppressed the PLC activation in Ca2+-deficient medium. Analogous suppressions were observed after loading cells with the Ca2+ chelator BAPTA. Stimulation of primary mouse pancreatic β-cells with glucagon elicited pronounced [Ca2+]i spikes, reflecting protein kinase A-mediated activation of Ca2+-induced Ca2+ release via IP3 receptors. These [Ca2+]i spikes were found to evoke rapid and transient activation of PLC. Our data indicate that receptor-triggered PLC activity is enhanced by positive feedback from Ca2+ entering the cytoplasm from intracellular stores and via store-operated channels in the plasma membrane. Such amplification of receptor signalling should be important in the regulation of insulin secretion by hormones and neurotransmitters.