bluuebunny/crossref_metadata_2025 huggingface dataset:
A Framework for Implementation-Independent Simulation Models
Authors: Larsson Jonas
Published: December 2006

Mathematical modeling and the simulation of complex physical systems is a central activity in engineering. The models are the result of large investments in time and measurement equipment and therefore need to be used as efficiently as possible. If one and the same model can be run in several simulation environments and in other applications, then the model can be simulated today and tomorrow in the most appropriate environment with respect to user background, the engineering domain at hand, and more. Modern equation-based modeling languages provide this functionality in principle since the models are translated into executable code by separate model compilers. These compilers today generate code for standalone simulation using a fixed interface toward a number of numerical solvers. What is missing is a compiler that can generate customized code for various simulation environments, where the generated code interfaces with other models in the environment through the conventional solution of powerports. Each port holds both input and output variables such as force and velocity. A compiler architecture is proposed in this article. Also, an implementation for a subset of the Modelica language is demonstrated in the case of two widely different simulation environment targets. The model ports are adapted initially to the simulation environment characteristics in terms of the variables part of the ports, and an input-output causality is found for which the model can be solved and that suits the environment. The equation system is optimized, and information such as Jacobians, assignments, and more is generated in the XML format. Finally, code generators specific for each environment are employed that create the final executable code.
Behavior Representation and Simulation for Military Operations on Urbanized Terrain
Authors: Shen Zhuoqian , Zhou Suiping
Published: December 2006

Generating human-like behaviors in a virtual warfare environment is still a challenging task to date. In this article, the authors present their work on the design of an artificial intelligence (AI) framework for the bots in military operations on urbanized terrain (MOUT) simulations.Their framework is designed to be flexible, extensible, integrable, and independent of simulation platforms. For fast prototyping, the AI framework is implemented on the Unreal Tournament (UT) game engine. A case study has been conducted that shows that the framework is effective and efficient in generating realistic bot behaviors in various combat scenarios.
Real-time measurement of melt viscosity in single-screw extrusion
Authors: McAfee M. , McNally G.
Published: December 2006

This paper examines the issues associated with the real-time measurement of viscosity in a single-screw extruder. To this end, the static and dynamic performance of a side-stream and in-line rheometer are compared. Side-stream sampling techniques were shown to be inappropriate for accurate detection of process dynamics. In-line rheometers may detect process dynamics but there are practical limitations on their use in an industrial environment.
Classification as an aid tool for the selection of sensors used for fault detection and isolation
Authors: Orantes A. , Kempowsky T. , Le Lann M.-V.
Published: December 2006

Complex industrial processes demand significant financial investment in sensors and automation devices to monitor and supervise the process in order to guarantee the production quality and the plant and operators safety. Fault detection is one of the multiple tasks of process monitoring and it critically depends on the sensors that measure the significant process variables. Nevertheless, most of the work on fault detection and diagnosis found in literature place more emphasis on developing procedures to perform diagnosis given a set of sensors, and less on determining the actual location of sensors for efficient identification of faults. A methodology based on learning and classification techniques and the information quantity measure, by the entropy concept, is proposed in order to address the problem of sensor location for fault identification. The proposed methodology has been applied to a new concept of intensification reactor, the Open Plate Reactor, developed by Alfa Laval and the Laboratory of Chemical Engineering located at Toulouse.
Identification of power disturbances using the morphological transform
Authors: Lu Z. , Smith J. S. , Wu Q. H. , Fitch J.
Published: December 2006

Power disturbances have always been represented a major issue to electricity consumers at all levels of usage. This paper presents a new method, based on mathematical morphology, for the detection and classification of power disturbances online. The proposed morphological transform technique extracts the features of disturbances from the signals in the time domain and detects the location and duration of the disturbances. A variety of power disturbances has been simulated to evaluate the validity of the technique. The advantages of the technique are also addressed in comparison with the wavelet transform.
Mothers' Favoritism in Later Life
Authors: Suitor J. Jill , Pillemer Karl
Published: December 2006

The authors used data on 426 older mothers' relationships with their 1,823 adult children to explore the relationship between birth order and parental favoritism. The findings demonstrate that birth order continues to play an important role in explaining favoritism when families enter later stages of the life course. Last-born adult children were most likely to be named as those to whom their mothers were most emotionally close; firstborn children were most likely to be chosen as those to whom mothers would turn when facing personal problems or crises. Further analyses revealed that these patterns remained largely unaffected by family size, race, and child spacing. Middleborn children were substantially underrepresented in mothers' choices; such a pattern is particularly striking considering that the number of middle-born children far exceeded that of firstborn and last-born children in the sample.
Education and Cognitive Decline in Older Americans
Authors: Alley Dawn , Suthers Kristen , Crimmins Eileen
Published: December 2006

Although education is consistently related to better cognitive performance, findings on the relationship between education and age-associated cognitive change have been conflicting. Using measures of multiple cognitive domains from four waves of the Asset and Health Dynamics of the Oldest Old study, a representative sample of Americans aged 70 years and older, the authors performed growth curve modeling to examine the relationships between education, initial cognitive score, and the rate of decline in cognitive function. More years of education were linked to better initial performance on each of the cognitive tests, and higher levels of education were linked to slower decline in mental status. However, more education was unrelated to the rate of decline in working memory, and education was associated with somewhat faster cognitive decline on measures of verbal memory. These findings highlight the role of early-life experiences not only in long-term cognitive performance but also in old-age cognitive trajectories.
Autonomy, Responsibility and the Italian Code of Deontology for Nurses
Authors: Barazzetti Gaia , Radaelli Stefania , Sala Roberta
Published: December 2006

This article is a first assessment of the Italian Code of deontology for nurses (revised in 1999) on the basis of data collected from focus groups with nurses taking part in the Ethical Codes in Nursing (ECN) project. We illustrate the professional context in which the Code was introduced and explain why the 1999 revision was necessary in the light of changes affecting the Italian nursing profession. The most remarkable findings concern professional autonomy and responsibility, and how the Code is thought of as a set of guidelines for nursing practice. We discuss these issues, underlining that the 1999 Code represents a valuable instrument for ethical reflection and examination, a stimulus for putting the moral sense of the nursing profession into action, and that it represents a new era for professional nursing practice in Italy. The results of the analysis also deserve further qualitative study and future consideration.
Factors Predicting Nurses' Consideration of Leaving their Job During the Sars Outbreak
Authors: Shiao Judith Shu-Chu , Koh David , Lo Li-Hua , Lim Meng-Kin , Guo Yueliang Leon
Published: December 2006

Taiwan was affected by an outbreak of severe acute respiratory syndrome (SARS) in early 2003. A questionnaire survey was conducted to determine (1) the perceptions of risk of SARS infection in nurses; (2) the proportion of nurses considering leaving their job; and (3) work as well as non-work factors related to nurses' consideration of leaving their job because of the SARS outbreak. Nearly three quarters (71.9%) of the participants believed they were 'at great risk of exposure to SARS', 49.9% felt'an increase in workload', and 32.4% thought that people avoided them because of their job; 7.6% of the nurses not only considered that they should not care for SARS patients but were looking for another job or considering resignation. The main predictors of nurses' consideration of leaving their job were shorter tenure, increased work stress, perceived risk of fatality from SARS, and affected social relationships. The findings are important in view of potential impending threats of pandemics such as avian influenza.
Consent and Assent to Participate in Research from People with Dementia
Authors: Slaughter Susan , Cole Dixie , Jennings Eileen , Reimer Marlene A
Published: December 2006

Conducting research with vulnerable populations involves careful attention to the interests of individuals. Although it is generally understood that informed consent is a necessary prerequisite to research participation, it is less clear how to proceed when potential research participants lack the capacity to provide this informed consent. The rationale for assessing the assent or dissent of vulnerable individuals and obtaining informed consent by authorized representatives is discussed. Practical guidelines for recruitment of and data collection from people in the middle or late stage of dementia are proposed. These guidelines were used by research assistants in a minimal risk study.
The Terminal: A tale of virtue
Authors: Austin Wendy
Published: December 2006

The movie, The terminal, is used to illustrate Mac Intyre's description of virtue ethics. The terminal is a mythical tale about a traveler, Viktor Navorski, who is stranded by circumstances in a New York airport. Viktor is a person who, without a strict reliance on duty or rules, has developed the disposition to act well despite variation in his circumstances. His character is revealed in contrast to that of three other characters: a cleaner, a flight attendant and the airport manager. Stories like this one may be a good way to open dialogue among clinicians about being virtuous as a practitioner. Such dialogue may make striving to be virtuous an acceptable goal for practitioners and less like an idealistic, pseudo-goal for those aiming for sainthood.
QALY: An Ethical Issue that Dare Not Speak its Name
Authors: Hirskyj Peter
Published: December 2006

The current British Government's policy towards resource allocation for health care has been informed by the commissioned Wanless Report. This makes a case for the use of quality adjusted life years (QALYs) to form a rationale for resourcing health care and has implications for the staff and patients who work in and use the health service. This article offers a definition of the term ‘QALY’ and considers some of the strengths and weaknesses of this approach to resource distribution. An account is also given of an alternative formula, the DALY (disability adjusted life years), which can address some of the problems that are associated with QALYs. The values of the public, patients and nurses are identified and linked to the potential effect of a QALY formula. The implications of QALY use are applied to the health care of patients and a discussion is offered with regard to whether this method of resource allocation can be considered as just.
On defining marketing: finding a new roadmap for marketing
Authors: Grönroos Christian
Published: December 2006

The American Marketing Association has updated its marketing definition and included value for customers and customer relationships in the new definition. Moreover, marketing is defined as one organizational function. Taking mainly service and relationship marketing research as a starting point, this present article broadens the discussion to a generic marketing level, and analyses the underpinning logic of the updated definition. It concludes that the use of these elements of the definition is not well founded in current research. Also, it shows that marketing cannot be treated as one organizational function only. Drawing on the analysis of the updated definition, a set of propositions regarding the scope and content of a marketing definition are developed. Finally, based on the analysis and this set of propositions, an alternative marketing definition, based on the promise concept, and labelled a promises management definition, is suggested and its implications for marketing research and practice are discussed.
Conceptualizing product quality: the case of wine
Authors: Charters Steve , Pettigrew Simone
Published: December 2006

This study investigated wine drinkers' perspectives on how product quality is conceptualized. The research was carried out because the dominant paradigm for quality within the marketing literature is perceived quality, and as such it is important to understand how consumers construct frameworks to understand quality and specifically whether they share this perception of the particular importance of the notion of perceived quality. Qualitative processes were used to obtain data from 60 informants. The findings indicate that consumers can adopt subjective or objective frameworks, with some also leaning towards relative and absolute quality positions. These conflicting frameworks are resolved by using an interactionist perspective, which allows quality to mediate the varying quality correlates noted in the marketing literature.
Heaven knows I'm miserable now
Authors: Shankar Avi , Whittaker Julie , Fitchett James A.
Published: December 2006

In this article, marketing is considered a tool for performing the economy, a means by which a particular economic and political ideology has been reproduced and disseminated. Despite the early success of this project in improving and progressing the quality of peoples' lives, it is doubtful that this progress can be sustained in the 21st century. Marketing and its technologies are fundamental to sustaining economic growth, yet the provision of more goods and services into the marketplace–the provision of more choice–appears not to deliver on its theoretical promise of making people happier with their lives. The source of this discontent is examined from a psychoanalytical perspective.
Interferon regulatory factor 3-dependent responses to lipopolysaccharide are selectively blunted in cord blood cells
Authors: Aksoy Ezra , Albarani Valentina , Nguyen Muriel , Laes Jean-Francois , Ruelle Jean-Louis , De Wit Dominique , Willems Fabienne , Goldman Michel , Goriely Stanislas
Published: December 2006

The synthesis of interferon-β (IFNβ) and IFN-inducible factors elicited by lipopolysaccharide (LPS) depends on the transcriptional activity of interferon regulatory factor 3 (IRF-3) downstream of Toll-like receptor-4 (TLR4). To examine the ability of human newborns to mount TLR4-mediated IRF-3–dependent responses, we analyzed the pattern of genes expressed on the addition of LPS to cord blood or cord blood monocyte-derived dendritic cells (moDCs). Expression of IFNβ and IFN-inducible genes was selectively impaired in neonatal blood and moDCs as compared with their adult counterparts. This selective defect was confirmed by microarray experiments on moDCs. Altered expression of IFN-inducible genes was related to impaired IFNβ synthesis because IFNβ signaling was functional in neonatal moDCs. However, addition of exogenous IFNβ failed to restore LPS-induced IL-12p70 synthesis which was previously shown to be defective in neonatal moDCs. Although LPS-induced IRF-3 nuclear translocation was observed both in adult and neonatal moDCs, IRF-3 DNA-binding activity and association with the coactivator CREB-binding protein (CBP) were decreased in neonatal as compared with adult moDCs. We conclude that impaired IRF-3/CBP interaction in neonatal blood cells exposed to LPS is associated with impaired expression of IFNβ and IFN-inducible genes. Because IRF-3 activity is also required for IL-12p70 synthesis, our findings provide a molecular basis for the decreased ability of LPS-stimulated neonatal moDCs to elicit Th1-type responses.
Hyperacute GVHD: risk factors, outcomes, and clinical implications
Authors: Saliba Rima M. , de Lima Marcos , Giralt Sergio , Andersson Borje , Khouri Issa F. , Hosing Chitra , Ghosh Shubhra , Neumann Joyce , Hsu Yvonne , De Jesus Jorge , Qazilbash Muzaffar H. , Champlin Richard E. , Couriel Daniel R.
Published: December 2006

Acute graft-versus-host disease (GVHD) is a major limiting factor in allogeneic hematopoietic stem cell transplantation (HSCT), and the timing of acute GVHD may affect patient outcomes. We evaluated the incidence, risk factors, clinical manifestations, and outcomes of hyperacute GVHD, defined as that occurring within 14 days after transplantation, among 809 consecutive HSCTs at the University of Texas M. D. Anderson Cancer Center. Of 265 patients with grade II-IV acute GVHD, 27% had biopsy-proven hyperacute GVHD. Skin involvement was significantly more common (88% versus 44%) and more severe (stage III-IV, 88% versus 66%) in the hyperacute group compared with acute GVHD diagnosed after day 14. On multivariate analysis, significant risk factors for hyperacute GVHD included a mismatched related or matched unrelated donor, a myeloablative conditioning regimen, more than 5 prior chemotherapy regimens, and donor-recipient sex mismatch. Hyperacute GVHD was associated with a significantly lower response rate to first-line therapy and a higher rate of nonrelapse mortality in patients with a mismatched related or matched unrelated donor graft. In conclusion, hyperacute GVHD accounts for a substantial proportion of grade II-IV acute GVHD after HSCT. Patients at high risk or with a diagnosis of hyperacute GVHD should be included in clinical studies.
Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats
Authors: Schurgers Leon J. , Spronk Henri M. H. , Soute Berry A. M. , Schiffers Paul M. , DeMey Jo G. R. , Vermeer Cees
Published: December 2006

Arterial calcification (AC) is generally regarded as an independent risk factor for cardiovascular morbidity and mortality. Matrix Gla protein (MGP) is a potent inhibitor of AC, and its activity depends on vitamin K (VK). In rats, inactivation of MGP by treatment with the vitamin K antagonist warfarin leads to rapid calcification of the arteries. Here, we investigated whether preformed AC can be regressed by a VK-rich diet. Rats received a calcification-inducing diet containing both VK and warfarin (W&K). During a second 6-week period, animals were randomly assigned to receive either W&K (3.0 mg/g and 1.5 mg/g, subsequently), a diet containing a normal (5 μg/g) or high (100 μg/g) amount of VK (either K1 or K2). Increased aortic calcium concentration was observed in the group that continued to receive W&K and also in the group changed to the normal dose of VK and AC progressed. Both the VK-rich diets decreased the arterial calcium content by some 50%. In addition, arterial distensibility was restored by the VK-rich diet. Using MGP antibodies, local VK deficiency was demonstrated at sites of calcification. This is the first study in rats demonstrating that AC and the resulting decreased arterial distensibility are reversible by high-VK intake.
IRF-4 and c-Rel expression in antiviral-resistant adult T-cell leukemia/lymphoma
Authors: Ramos Juan Carlos , Ruiz Phillip , Ratner Lee , Reis Isildinha M. , Brites Carlos , Pedroso Celia , Byrne Gerald E. , Toomey Ngoc L. , Andela Valentine , Harhaj Edward W. , Lossos Izidore S. , Harrington William J.
Published: December 2006

Adult T-cell leukemia/lymphoma (ATLL) is a generally fatal malignancy. Most ATLL patients fare poorly with conventional chemotherapy; however, antiviral therapy with zidovudine (AZT) and interferon alpha (IFN-α) has produced long-term clinical remissions. We studied primary ATLL tumors and identified molecular features linked to sensitivity and resistance to antiviral therapy. Enhanced expression of the proto-oncogene c-Rel was noted in 9 of 27 tumors. Resistant tumors exhibited c-Rel (6 of 10; 60%) more often than did sensitive variants (1 of 9; 11%). This finding was independent of the disease form. Elevated expression of the putative c-Rel target, interferon regulatory factor-4 (IRF-4), was observed in 10 (91%) of 11 nonresponders and in all tested patients with c-Rel+ tumors and occurred in the absence of the HTLV-1 oncoprotein Tax. In contrast, tumors in complete responders did not express c-Rel or IRF-4. Gene rearrangement studies demonstrated the persistence of circulating T-cell clones in long-term survivors maintained on antiviral therapy. The expression of nuclear c-Rel and IRF-4 occurs in the absence of Tax in primary ATLL and is associated with antiviral resistance. These molecular features may help guide treatment. AZT and IFN-α is a suppressive rather than a curative regimen, and patients in clinical remission should remain on maintenance therapy indefinitely.
Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents
Authors: Cairo Mitchell S. , Gerrard Mary , Sposto Richard , Auperin Anne , Pinkerton C. Ross , Michon Jean , Weston Claire , Perkins Sherrie L. , Raphael Martine , McCarthy Keith , Patte Catherine ,   on behalf of the FAB LMB96 International Study Committee
Published: December 2006

The prognosis for higher risk childhood B-cell non-Hodgkin lymphoma has improved over the past 20 years but the optimal intensity of treatment has yet to be determined. Children 21 years old or younger with newly diagnosed B-cell non-Hodgkin lymphoma/B-cell acute lymphoblastic leukemia (B-NHL/B-ALL) with higher risk factors (bone marrow [BM] with or without CNS involvement) were randomized to standard intensity French-American-British/Lymphoma Malignancy B (FAB/LMB) therapy or reduced intensity (reduced cytarabine plus etoposide and deletion of 3 maintenance courses M2, M3, M4). All patients with CNS disease had additional high-dose methotrexate (8 g/m2) plus extra intrathecal therapy. Fifty-one percent had BM involvement, 20% had CNS involvement, and 29% had BM and CNS involvement. One hundred ninety patients were randomized. The probabilities of 4-year event-free survival (EFS) and survival (S) were 79% ± 2.7% and 82% ± 2.6%, respectively. In patients in remission after 3 cycles who were randomized to standard versus reduced-intensity therapy, the 4-year EFS after randomization was 90% ± 3.1% versus 80% ± 4.2% (one-sided P = .064) and S was 93% ± 2.7% versus 83% ± 4.0% (one-sided P = .032). Patients with either combined BM/CNS disease at diagnosis or poor response to cyclophosphamide, Oncovin [vincristine], prednisone (COP) reduction therapy had a significantly inferior EFS and S (P < .001). Standard-intensity FAB/LMB therapy is recommended for children with high-risk B-NHL (B-ALL with or without CNS involvement).
Extended follow-up of methotrexate-free immunosuppression using sirolimus and tacrolimus in related and unrelated donor peripheral blood stem cell transplantation
Authors: Cutler Corey , Li Shuli , Ho Vincent T. , Koreth John , Alyea Edwin , Soiffer Robert J. , Antin Joseph H.
Published: December 2006

We assessed the combination of sirolimus and tacrolimus without methotrexate after myeloablative allogeneic stem cell transplantation from 53 matched related donors (MRDs) and 30 unrelated donors (URDs). All patients received cyclophosphamide and total body irradiation conditioning followed by transplantation of mobilized peripheral blood stem cells. The median time to neutrophil engraftment was 14 days. The median time to platelet engraftment was 12 days. No differences between MRD and URD cohorts was noted. The incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD) were 20.5% and 4.8%. The cumulative incidence of chronic GVHD was 59.1%. There were no differences in acute or chronic GVHD incidence between MRD and URD cohorts. The omission of methotrexate was associated with low transplant-related toxicity, with 30-day and 100-day treatment-related mortality rates of 0% and 4.8%. Relapse-free survival at 1 and 2 years was 72.3% and 68.5%, respectively. Overall survival at 1 and 2 years was 77.1% and 72.2%, respectively. There were no differences in relapse-free or overall survival between MRD and URD cohorts. The substitution of sirolimus for methotrexate as GVHD prophylaxis is associated with rapid engraftment, a low incidence of acute GVHD, minimal transplant-related toxicity, and excellent survival. Differences between MRD and URD cohorts are not evident when effective GVHD prophylaxis is used.
Activity and safety of bortezomib in multiple myeloma patients with advanced renal failure: a multicenter retrospective study
Authors: Chanan-Khan Asher A. , Kaufman Jonathan L. , Mehta Jayesh , Richardson Paul G. , Miller Kena C. , Lonial Sagar , Munshi Nikhil C. , Schlossman Robert , Tariman Joseph , Singhal Seema
Published: December 2006

Patients with multiple myeloma (MM) frequently present with concomitant renal dysfunction, and those requiring dialysis have particularly poor outcomes. Bortezomib is a reversible proteasome inhibitor with significant activity in MM. This retrospective case analysis evaluated the feasibility and activity of bortezomib-based therapy in MM patients (n = 24) requiring dialysis support for advanced renal failure. All but 1 patient were undergoing dialysis at the time of therapy. Patients received bortezomib alone or bortezomib-based combination therapy. Among 20 patients with available response data, overall response rate (complete response [CR] + partial response) was 75%, with 30% CR + near CR. One patient was spared dialysis, and 3 other patients became independent of dialysis following bortezomib-based treatment. These encouraging results suggest that bortezomib or bortezomib-based regimens can be used in MM patients requiring dialysis, with manageable toxicities. Further studies will more formally evaluate the impact of bortezomib-based regimens in this patient population.
Connectivity independent protein-structure alignment: a hierarchical approach
Authors: Kolbeck Bjoern , May Patrick , Schmidt-Goenner Tobias , Steinke Thomas , Knapp Ernst-Walter
Published: December 2006

Background

Protein-structure alignment is a fundamental tool to study protein function, evolution and model building. In the last decade several methods for structure alignment were introduced, but most of them ignore that structurally similar proteins can share the same spatial arrangement of secondary structure elements (SSE) but differ in the underlying polypeptide chain connectivity (non-sequential SSE connectivity).

Results

We perform protein-structure alignment using a two-level hierarchical approach implemented in the program GANGSTA. On the first level, pair contacts and relative orientations between SSEs (i.e. α-helices and β-strands) are maximized with a genetic algorithm (GA). On the second level residue pair contacts from the best SSE alignments are optimized. We have tested the method on visually optimized structure alignments of protein pairs (pairwise mode) and for database scans. For a given protein structure, our method is able to detect significant structural similarity of functionally important folds with non-sequential SSE connectivity. The performance for structure alignments with strictly sequential SSE connectivity is comparable to that of other structure alignment methods.

Conclusion

As demonstrated for several applications, GANGSTA finds meaningful protein-structure alignments independent of the SSE connectivity. GANGSTA is able to detect structural similarity of protein folds that are assigned to different superfamilies but nevertheless possess similar structures and perform related functions, even if these proteins differ in SSE connectivity.
iHAP – integrated haplotype analysis pipeline for characterizing the haplotype structure of genes
Authors: Song Chun Meng , Yeo Boon Huat , Tantoso Erwin , Yang Yuchen , Lim Yun Ping , Li Kuo-Bin , Rajagopal Gunaretnam
Published: December 2006

Background

The advent of genotype data from large-scale efforts that catalog the genetic variants of different populations have given rise to new avenues for multifactorial disease association studies. Recent work shows that genotype data from the International HapMap Project have a high degree of transferability to the wider population. This implies that the design of genotyping studies on local populations may be facilitated through inferences drawn from information contained in HapMap populations.

Results

To facilitate analysis of HapMap data for characterizing the haplotype structure of genes or any chromosomal regions, we have developed an integrated web-based resource, iHAP. In addition to incorporating genotype and haplotype data from the International HapMap Project and gene information from the UCSC Genome Browser Database, iHAP also provides capabilities for inferring haplotype blocks and selecting tag SNPs that are representative of haplotype patterns. These include block partitioning algorithms, block definitions, tag SNP definitions, as well as SNPs to be "force included" as tags. Based on the parameters defined at the input stage, iHAP performs on-the-fly analysis and displays the result graphically as a webpage. To facilitate analysis, intermediate and final result files can be downloaded.

Conclusion

The iHAP resource, available at http://ihap.bii.a-star.edu.sg, provides a convenient yet flexible approach for the user community to analyze HapMap data and identify candidate targets for genotyping studies.
Analyzing the dose-dependence of the Saccharomyces cerevisiae global transcriptional response to methyl methanesulfonate and ionizing radiation
Authors: Benton Michael G , Somasundaram Swetha , Glasner Jeremy D , Palecek Sean P
Published: December 2006

Background

One of the most crucial tasks for a cell to ensure its long term survival is preserving the integrity of its genetic heritage via maintenance of DNA structure and sequence. While the DNA damage response in the yeast Saccharomyces cerevisiae, a model eukaryotic organism, has been extensively studied, much remains to be elucidated about how the organism senses and responds to different types and doses of DNA damage. We have measured the global transcriptional response of S. cerevisiae to multiple doses of two representative DNA damaging agents, methyl methanesulfonate (MMS) and gamma radiation.

Results

Hierarchical clustering of genes with a statistically significant change in transcription illustrated the differences in the cellular responses to MMS and gamma radiation. Overall, MMS produced a larger transcriptional response than gamma radiation, and many of the genes modulated in response to MMS are involved in protein and translational regulation. Several clusters of coregulated genes whose responses varied with DNA damaging agent dose were identified. Perhaps the most interesting cluster contained four genes exhibiting biphasic induction in response to MMS dose. All of the genes (DUN1, RNR2, RNR4, and HUG1) are involved in the Mec1p kinase pathway known to respond to MMS, presumably due to stalled DNA replication forks. The biphasic responses of these genes suggest that the pathway is induced at lower levels as MMS dose increases. The genes in this cluster with a threefold or greater transcriptional response to gamma radiation all showed an increased induction with increasing gamma radiation dosage.

Conclusion

Analyzing genome-wide transcriptional changes to multiple doses of external stresses enabled the identification of cellular responses that are modulated by magnitude of the stress, providing insights into how a cell deals with genotoxicity.
Key transmission parameters of an institutional outbreak during the 1918 influenza pandemic estimated by mathematical modelling
Authors: Sertsou Gabriel , Wilson Nick , Baker Michael , Nelson Peter , Roberts Mick G
Published: December 2006

Aim

To estimate the key transmission parameters associated with an outbreak of pandemic influenza in an institutional setting (New Zealand 1918).

Methods

Historical morbidity and mortality data were obtained from the report of the medical officer for a large military camp. A susceptible-exposed-infectious-recovered epidemiological model was solved numerically to find a range of best-fit estimates for key epidemic parameters and an incidence curve. Mortality data were subsequently modelled by performing a convolution of incidence distribution with a best-fit incidence-mortality lag distribution.

Results

Basic reproduction number (R0) values for three possible scenarios ranged between 1.3, and 3.1, and corresponding average latent period and infectious period estimates ranged between 0.7 and 1.3 days, and 0.2 and 0.3 days respectively. The mean and median best-estimate incidence-mortality lag periods were 6.9 and 6.6 days respectively. This delay is consistent with secondary bacterial pneumonia being a relatively important cause of death in this predominantly young male population.

Conclusion

TheseR0estimates are broadly consistent with others made for the 1918 influenza pandemic and are not particularly large relative to some other infectious diseases. This finding suggests that if a novel influenza strain of similar virulence emerged then it could potentially be controlled through the prompt use of major public health measures.
How emergency departments might alert for prehospital heat-related excess mortality?
Authors: Claessens Yann-Erick , Taupin Pierre , Kierzek Gérald , Pourriat Jean-Louis , Baud Michel , Ginsburg Christine , Jais Jean-Philippe , Jougla Eric , Riou Bruno , Dhainaut Jean-François , Landais Paul
Published: December 2006

Introduction

A major issue raised by the public health consequences of a heat wave is the difficulty of detecting its direct consequences on patient outcome, particularly because of the delay in obtaining definitive mortality results. Since emergency department (ED) activity reflects the global increase of patients' health problems during this period, the profile of patients referred to EDs might be a basis to detect an excess mortality in the catchment area. Our objective was to develop a real-time surveillance model based on ED data to detect excessive heat-related mortality as early as possible.

Methods

A day-to-day composite indicator was built using simple and easily obtainable variables related to patients referred to the ED during the 2003 heat-wave period. The design involved a derivation and validation study based on a real-time surveillance system of two EDs at Cochin Hospital and Hôtel-Dieu Hospital, Paris, France. The participants were 99,976 adult patients registered from 1 May to 30 September during 2001, 2002 and 2003. Among these participants, 3,297, 3,580 and 3,851 patients were referred to the EDs from 3 August to 19 August for 2001, 2002 and 2003, respectively. Variables retained for the indicator were selected using the receiver operating characteristic curve methodology and polynomial regression.

Results

The indicator was composed of only three variables: the percentage of patients older than 70 years, the percentage of patients with body temperature above 39°C, and the percentage of patients admitted to or who died in the ED. The curve of the indicator with time appropriately fitted the overall mortality that occurred in the region of interest.

Conclusion

A composite and simple index based on real-time surveillance was developed according to the profile of patients who visited the ED. It appeared suitable for determining the overall mortality in the corresponding region submitted to the 2003 heat wave. This index should help early warning of excessive mortality and monitoring the efficacy of public health interventions.
Evaluation of furosemide regimens in neonates treated with extracorporeal membrane oxygenation
Authors: van der Vorst Maria MJ , Wildschut Enno , Houmes Robbert J , Gischler Saskia J , Kist-van Holthe Joana E , Burggraaf Jacobus , van der Heijden Albert J , Tibboel Dick
Published: December 2006

Introduction

Loop diuretics are the most frequently used diuretics in patients treated with extracorporeal membrane oxygenation (ECMO). In patients after cardiopulmonary bypass (CPB) surgery, the use of continuous furosemide infusion is increasingly documented. Because ECMO and CPB are 'comparable' procedures, continuous furosemide infusion is used in newborns on ECMO. We report on the use of continuous intravenous furosemide in neonates treated with ECMO.

Methods

This was a retrospective observational study in neonates treated with continuous intravenous furosemide during ECMO.

Results

Thirty-one patients were included in the study. A median of 25 (9–149) hours after the start of ECMO, continuous furosemide therapy was started at a median rate of 0.08 (0.02–0.17) mg/kg per hour. The continuous furosemide dose was not changed in the individual patient. Seven patients received a furosemide bolus prior to, and five patients received additional loop diuretics during, the continuous infusion. Urine production before continuous furosemide therapy was not significantly different between patients who received a furosemide bolus prior to the infusion and those who did not receive this bolus (P = 0.2879). Although a positive effect of the 'loading' bolus was observed in urine output in the first 24 hours, there was no statistically significant difference in urine output (P = 0.0961) or in time (P = 0.1976) to reach a urine output of 6 ml/kg per hour between patients. After 24 hours, urine production remained a median of 6.2 ml/kg per hour irrespective of furosemide boluses. The forced diuresis was well tolerated as illustrated by stable haemodynamic parameters and a decrease in ECMO flow and vasopressor score over the observation period.

Conclusion

This is the first report on continuous intravenous furosemide therapy in newborns treated with ECMO. The furosemide regimens used in this study varied widely in continuous and intermittent doses. However, all regimens achieved adequate urine output. An advantage of continuous, over intermittent, intravenous furosemide could not be documented. Furosemide dosing regimens should be developed for neonates treated with ECMO. In addition, therapeutic drug-monitoring studies are required to prevent furosemide toxicity because so far no data are available on serum furosemide levels in neonates treated with ECMO.
The National Audit of Violence: in-patient care for adults of working age
Authors: Chaplin Robert , McGeorge Maureen , Lelliott Paul
Published: December 2006

Aims and Method

We audited 184 psychiatric wards against clinical practice guidelines for the management of violence. Staff and service users completed anonymous questionnaires. Environmental inspections were performed by two teams.

Results

There were 4460 questionnaires returned. Nurses (78%) were significantly more likely to report the experience of violence than service users (37%). Drugs were reported by 72% of nurses and alcohol by 61% as causing problems. Other standards frequently not met included staffing levels, training, provision of activities, ward design and ambience.

Clinical Implications

Specific issues are identified that must be addressed by national and local action. A baseline is set against which the impact of this action can be judged. Priorities must include tackling drug and alcohol use in psychiatric wards.
Quality of referrals to old age psychiatry following introduction of the single assessment process
Authors: Ferriter Kathleen , Gangopadhyay Partha , Nilforooshan Ramin , Ardern Mark , Warner James
Published: December 2006

Aims and Method

We sought to identify changes in the quality of information in referrals to an old age psychiatry service before and after the introduction of the single assessment process. Referrals were compared in terms of length, legibility, information and clinical utility.

Results

Compared with letters before the introduction of the single assessment process, referrals made on the new forms took longer to read (mean 96 v. 124 s, P=0.001), had more illegible sections (P=0.011), contained less information (P=0.026) and were judged to be less clinically useful (P=0.001).

Clinical Implications

The introduction of the single assessment process has impaired clinical communication between general practitioners and psychiatrists, and might be prejudicial to patient care.
When mountains weep: psychological care for those affected by the earthquake in northern Pakistan
Authors: Khan Murad M.
Published: December 2006

Fate, it seems, conjures up all sorts of ways for us to be in a certain place at a certain time. In 1982 as a trainee psychiatrist in the UK, I found myself co-facilitating a group at the Castlewood Day Hospital, then part of the Bexley psychiatric rotation scheme, in the south-east of London. Group psychotherapy was part of our training. Held thrice a week the groups were open-ended and patients ranged from those with interpersonal relationship and personality problems to those with anxiety and substance misuse problems. At the time the experience was somewhat baffling. Not only was I from a different country and culture, my exposure to psychiatry was limited to about 12 months. More often than not I felt lost as I tried to come to terms with ‘group dynamics', ‘reality testing’, ‘transference’, ‘multiple transference’, ‘group cohesion’, ‘group pressure’, etc.
Service innovations: developing a service for the mental health needs of South-Asian children and adolescents
Authors: Hackett Latha , Theodosiou Louise , Patel Jamila
Published: December 2006

Over recent years there has been concern regarding health service accessibility for minority ethnic groups and this was reflected in the introduction of mandatory recordings of patient ethnicity upon hospital admission (Giu & Johnson, 1995).
No dogs. Guide dogs by prior permission
Authors: Pease James , Brown Anthony
Published: December 2006

Esther Rantzen created the Jobsworth Award before the National Health Service (NHS) invented clinical governance. One wonders sometimes if the NHS would have scooped all their awards had the programme continued. Television presenters also caution against involvement with children or animals, or worst of all both simultaneously. Clearly child and adolescent mental health professionals planning to involve animals in therapy should be cautious even in a semi-rural locality. Animals and children are, however, within our knowledge and skills framework, but not so the finer points of clinical governance.
Undernutrition in Utero Augments Systolic Blood Pressure and Cardiac Remodeling in Adult Mouse Offspring: Possible Involvement of Local Cardiac Angiotensin System in Developmental Origins of Cardiovascular Disease
Authors: Kawamura Makoto , Itoh Hiroaki , Yura Shigeo , Mogami Haruta , Suga Shin-Ichi , Makino Hisashi , Miyamoto Yoshihiro , Yoshimasa Yasunao , Sagawa Norimasa , Fujii Shingo
Published: December 2006

Evidence has emerged that undernutrition in utero is a risk factor for cardiovascular disorders in adulthood, along with genetic and environmental factors. Recently, the local expression of angiotensinogen and related bioactive substances has been demonstrated to play a pivotal role in cardiac remodeling, i.e. fibrosis and hypertrophy. The aim of the present study was to clarify the possible involvement of the local cardiac angiotensin system in fetal undernutrition-induced cardiovascular disorders. We developed a mouse model of undernutrition in utero by maternal food restriction, in which offspring (UN offspring) showed an increase in systolic blood pressure (8 wk of age, P < 0.05; and 16 wk, P < 0.01), perivascular fibrosis of the coronary artery (16 wk, P < 0.05) and cardiac cardiomegaly (16 wk, P < 0.01), and cardiomyocyte enlargement, concomitant with a significant augmentation of angiotensinogen (P < 0.05) and endothelin-1 (P < 0.01) mRNA expression and a tendency to increase in immunostaining for both angiotensin II and endothelin-1 in the left ventricles (16 wk). These findings suggest that fetal undernutrition activated the local cardiac angiotensin system-associated bioactive substances, which contributed, at least partly, to the development of cardiac remodeling in later life, in concert with the effects of increase in blood pressure.
Dynamic Changes in the Cervical Epithelial Tight Junction Complex and Differentiation Occur during Cervical Ripening and Parturition
Authors: Timmons Brenda C. , Mitchell Shannon M. , Gilpin Christopher , Mahendroo Mala S.
Published: December 2006

Cervical epithelia have numerous functions that include proliferation, differentiation, maintenance of fluid balance, protection from environmental hazards, and paracellular transport of solutes via tight junctions (TJs). Epithelial functions must be tightly regulated during pregnancy and parturition as the cervix undergoes extensive growth and remodeling. This study evaluated TJ proteins, as well as markers of epithelial cell differentiation in normal and cervical ripening defective mice to gain insights into how the permeability barrier is regulated during pregnancy and parturition. Although numerous TJ proteins are expressed in the nonpregnant cervix, claudins 1 and 2 are temporally regulated in pregnancy. Claudin 1 mRNA expression is increased, whereas claudin 2 expression declines. The cellular localization of claudin 1 shifts at the end of pregnancy (gestation d 18.75) to the plasma membrane in a lattice pattern, consistent with TJs in the apical cells. The timing of claudin 1-enriched TJs coincides with initiation of terminal differentiation of cervical squamous epithelia as evidenced by the increased expression of genes by differentiated epithelia late on gestation d 18. The cervical ripening defective steroid 5α-reductase type 1 deficient mouse, which has an elevated local progesterone concentration, also has aberrant claudin 1 and 2 expressions, fails to form claudin 1-enriched TJs, and lacks normal expression of genes involved in epithelial terminal differentiation. These data suggest that changes in permeability barrier properties during cervical ripening are, in part, negatively regulated by progesterone, and that dynamic changes in barrier properties of the cervix occur during pregnancy and parturition.