bluuebunny/crossref_metadata_2025 huggingface dataset:
Importance of the Cutoff Value in the Quadratic Adaptive Integrate-and-Fire Model
Authors: Touboul Jonathan
Published: May 2009

The quadratic adaptive integrate-and-fire model (Izhikevich, 2003 , 2007 ) is able to reproduce various firing patterns of cortical neurons and is widely used in large-scale simulations of neural networks. This model describes the dynamics of the membrane potential by a differential equation that is quadratic in the voltage, coupled to a second equation for adaptation. Integration is stopped during the rise phase of a spike at a voltage cutoff value Vc or when it blows up. Subsequently the membrane potential is reset, and the adaptation variable is increased by a fixed amount. We show in this note that in the absence of a cutoff value, not only the voltage but also the adaptation variable diverges in finite time during spike generation in the quadratic model. The divergence of the adaptation variable makes the system very sensitive to the cutoff: changing Vc can dramatically alter the spike patterns. Furthermore, from a computational viewpoint, the divergence of the adaptation variable implies that the time steps for numerical simulation need to be small and adaptive. However, divergence of the adaptation variable does not occur for the quartic model (Touboul, 2008 ) and the adaptive exponential integrate-and-fire model (Brette & Gerstner, 2005 ). Hence, these models are robust to changes in the cutoff value.
Quantifying Statistical Interdependence by Message Passing on Graphs—Part II: Multidimensional Point Processes
Authors: Dauwels J. , Vialatte F. , Weber T. , Musha T. , Cichocki A.
Published: May 2009

Stochastic event synchrony is a technique to quantify the similarity of pairs of signals. First, events are extracted from the two given time series. Next, one tries to align events from one time series with events from the other. The better the alignment, the more similar the two time series are considered to be. In Part I, the companion letter in this issue, one-dimensional events are considered; this letter concerns multidimensional events. Although the basic idea is similar, the extension to multidimensional point processes involves a significantly more difficult combinatorial problem and therefore is nontrivial. Also in the multidimensional case, the problem of jointly computing the pairwise alignment and SES parameters is cast as a statistical inference problem. This problem is solved by coordinate descent, more specifically, by alternating the following two steps: (1) estimate the SES parameters from a given pairwise alignment; (2) with the resulting estimates, refine the pairwise alignment. The SES parameters are computed by maximum a posteriori (MAP) estimation (step 1), in analogy to the one-dimensional case. The pairwise alignment (step 2) can no longer be obtained through dynamic programming, since the state space becomes too large. Instead it is determined by applying the max-product algorithm on a cyclic graphical model. In order to test the robustness and reliability of the SES method, it is first applied to surrogate data. Next, it is applied to detect anomalies in EEG synchrony of mild cognitive impairment (MCI) patients. Numerical results suggest that SES is significantly more sensitive to perturbations in EEG synchrony than a large variety of classical synchrony measures.
Fully Automated Detection of Cloud and Aerosol Layers in the CALIPSO Lidar Measurements
Authors: Vaughan Mark A. , Powell Kathleen A. , Winker David M. , Hostetler Chris A. , Kuehn Ralph E. , Hunt William H. , Getzewich Brian J. , Young Stuart A. , Liu Zhaoyan , McGill Matthew J.
Published: May 2009

Accurate knowledge of the vertical and horizontal extent of clouds and aerosols in the earth’s atmosphere is critical in assessing the planet’s radiation budget and for advancing human understanding of climate change issues. To retrieve this fundamental information from the elastic backscatter lidar data acquired during the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) mission, a selective, iterated boundary location (SIBYL) algorithm has been developed and deployed. SIBYL accomplishes its goals by integrating an adaptive context-sensitive profile scanner into an iterated multiresolution spatial averaging scheme. This paper provides an in-depth overview of the architecture and performance of the SIBYL algorithm. It begins with a brief review of the theory of target detection in noise-contaminated signals, and an enumeration of the practical constraints levied on the retrieval scheme by the design of the lidar hardware, the geometry of a space-based remote sensing platform, and the spatial variability of the measurement targets. Detailed descriptions are then provided for both the adaptive threshold algorithm used to detect features of interest within individual lidar profiles and the fully automated multiresolution averaging engine within which this profile scanner functions. The resulting fusion of profile scanner and averaging engine is specifically designed to optimize the trade-offs between the widely varying signal-to-noise ratio of the measurements and the disparate spatial resolutions of the detection targets. Throughout the paper, specific algorithm performance details are illustrated using examples drawn from the existing CALIPSO dataset. Overall performance is established by comparisons to existing layer height distributions obtained by other airborne and space-based lidars.
Injuries From Furniture Tip-overs Among Children and Adolescents in the United States, 1990-2007
Authors: Gottesman Bethany L. , McKenzie Lara B. , Conner Kristen A. , Smith Gary A.
Published: May 2009

Objective. To describe the epidemiology of pediatric injuries associated with furniture tip-overs in the United States. Methods. Data from the National Electronic Injury Surveillance System were analyzed for patients ≤17 years treated in emergency departments for a furniture tip-over-related injury from 1990 through 2007. Results. An estimated 264 200 furniture tip-over-related injuries occurred during the study period, yielding an average of 14 700 injuries annually, or 20.7 per 100 000 population per year. There was a significant increase in the number and rate of these injuries during the 18-year period. Three-quarters of injuries were to children ≤6 years. Televisions were the item most commonly involved (47.4%). Head/neck injuries were the most common (42.2%) injury type among children 0 to 9 years of age. Conclusions . The number and rate of injuries to children associated with furniture tip-overs are increasing. Pediatricians and caregivers should be aware of this important source of pediatric injury and the strategies for prevention.
The semi-autonomous judge in colonial India
Authors: Sharafi Mitra
Published: May 2009

Through a survey of 19 leading cases on Islamic dower and divorce between 1855 and 1924, this article explores the ways in which judges acted as semi-autonomous agents by undermining the colonial legislation and personal law treatises they were expected to apply. Contrary to the view that colonial judges consistently reinforced the patriarchal authority of husbands in direct and immediate ways, it suggests that some colonial judges were working in the service of their own chivalric imperialist agenda: the defence of Muslim wives. The article focuses on two particular moves. First, colonial judges encouraged the use of inflated dower, a device intended to make the husband's power of triple talāq too expensive to use. Colonial legislators invalidated inflated dower in various parts of India, but judges confirmed the validity of inflated dower sums whenever possible. Second, judges expanded the use of delegated divorce, a device that helped Muslim wives counter their husbands' right to polygamy and unilateral divorce. In doing so, judges undermined the restricted approach to delegation taken by colonial treatises on Anglo-Islamic law.
The Dynamics of Violence in Vietnam: An Analysis of the Hamlet Evaluation System (HES)
Authors: Kalyvas Stathis N. , Kocher Matthew Adam
Published: May 2009

The authors analyze a unique data source to study the determinants of violence against civilians in a civil war context. During the Vietnam War, the United States Department of Defense pioneered the use of quantitative analysis for operational purposes. The centerpiece of that effort was the Hamlet Evaluation System (HES), a monthly and quarterly rating of `the status of pacification at the hamlet and village level throughout the Republic of Vietnam'. Consistent with existing theoretical claims, the authors find that homicidal violence against civilians was a function of the level of territorial control exercised by the rival sides: Vietnamese insurgents relied on selective violence primarily where they enjoyed predominant, but not full, control; South Vietnamese government and US forces exercised indiscriminate violence primarily in the most rebel-dominated areas. Violence was less common in the most contested areas. The absence of spatial overlap between insurgent selective and incumbent indiscriminate violence, as well as the relative absence of violence from contested areas, demonstrates both the fundamental divergence between irregular and conventional war and the need for cautious use of violent events as indicators of conflict.
Seeking Safety: Avoiding Displacement and Choosing Destinations in Civil Wars
Authors: Steele Abbey
Published: May 2009

Despite civil war violence, some civilians stay in their communities. Those who leave choose one of many possible destinations. Drawing on fieldwork in Colombia, this article argues that the way armed groups target civilians explains households' decisions about displacement. When groups of civilians are targeted based on a shared characteristic — `collective' targeting — their best options for avoiding violence differ from those targeted selectively or indiscriminately. This article outlines conditions under which people can stay in contexts of collective targeting, and where they are likely to go if these conditions are not met. A civilian facing collective targeting could move to a rival group's stronghold, cluster with others similarly targeted, or seek anonymity in a city or different region. Community characteristics, such as whether it is urban or rural, as well as macro characteristics of the war, such as whether or not there is an ascriptive cleavage, shape which decisions are relatively safest, which in turn leads to implications for aggregate patterns. For example, clustering together has a perverse effect: even though hiding among others with similar characteristics may reduce an individual's likelihood of suffering direct violence, the community may be more endangered as it is perceived to be affiliated with an armed group. This then leads to a cycle of collective targeting and displacement, which has important implications for the development of warfare. In turn, this cycle and related cleavage formation may have long-term impacts on postwar stability and politics.
Another Look at the Language Difficulties of International Students
Authors: Yanyin Zhang  , Yinan Mi
Published: May 2009

International students encounter language-related problems in their academic studies. Specific problem areas have been identified and possible underlying causes have been explored. The present study investigates the impact of two variables—length of study and academic disciplines—in relation to the problems. The findings from a survey and interview of 40 Chinese students at 8 Australian universities reveal that though listening and speaking pose a lot of difficulties for the majority of the informants, the difficulties are confined to the first 2 years, and they do not seem to affect the academic study of those informants in linguistically less demanding courses. Reading does not seem to be a problem area but writing does, across academic disciplines, defying the 2-year mark. These findings call for a more balanced and nuanced understanding of the language difficulties experienced by international students.
Impact of Biopsychosocial Factors on Chronic Pain in Persons With Myotonic and Facioscapulohumeral Muscular Dystrophy
Authors: Miró Jordi , Raichle Katherine A. , Carter Gregory T. , O'Brien Sarah A. , Abresch Richard T. , McDonald Craig M. , Jensen Mark P.
Published: May 2009

To assess the role of biopsychosocial factors in patients with type 1 myotonic and facioscapulohumeral muscular dystrophy (MMD1/FSHD) with chronic pain. Associations between psychosocial factors were found to be important in other samples of persons with pain and both psychological functioning and pain interference in a sample of patients suffering from MMD/FSHD. Prospective, multiple group, survey study of 182 patients with confirmed MMD1 and FSHD. Participants completed surveys assessing pain interference and psychological functioning, as well as psychosocial, demographic, and injury-related variables. Analyses indicated that greater catastrophizing was associated with increased pain interference and poorer psychological functioning, pain attitudes were significantly related to both pain interference and psychological functioning, and coping responses were significantly related only to pain interference. In addition, greater perceived social support was associated with better psychological functioning. The results support the use of studying pain in persons with MMD/FSHD from a biopsychosocial perspective, and the importance of identifying psychosocial factors that may play a role in the adjustment to and response to pain secondary to MMD/FSHD.
Seven-Year Follow-Up on Lopinavir/ Ritonavir Monotherapy
Authors: Pierone Gerald , Mieras Jeffrey , Martin Amber , Urban Theresa
Published: May 2009

Previous studies of lopinavir/ritonavir (LPV/r) monotherapy have shown that over 70% of patients achieved HIV RNA levels <500 copies/mL over a follow-up period of 48 to 96 weeks, but the long-term durability is undetermined. Herein, the authors report 2 patients that started LPV/r monotherapy after virologic failure on an NNRTIbased regimen and have been successfully treated for greater than 7 years. Both patients demonstrated long-term control of viral replication over the course of treatment, although the first patient had 3 viral load blips and the second had 1 blip under 400 copies/mL. Both patients had increases in CD4+ lymphocyte counts. The first patient from 96 cells/μL to 378 cells/μL and the second patient from 71 cells/μL to 411 cells/μL. To the authors knowledge, these 2 cases represent the longest experience with LPV/r monotherapy and provide some measure of reassurance about the durability of LPV/r for control of HIV replication.
Understanding the Advanced Signal Processing Technique of Real-Time Adaptive Filters
Authors: Ahman Hilary , Thompson Lindsay , Swarbrick Amy , Woodward Julie
Published: May 2009

Diagnostic ultrasound manufacturers are advancing the technology of sonographic systems, providing superior image quality and improving the diagnostic confidence for both sonographers and radiologists. Real-time adaptive filters (RTAFs) are perhaps the least known among the advanced signal processing techniques available on most modern sonography machines, which is further complicated by the fact that RTAF appears under various trademark names. Despite the different proprietary names, RTAFs generally employ a postprocessing mathematical algorithm to real-time imaging that improves contrast resolution by reducing noise and artifacts while simultaneously enhancing the edges and smoothing the tissue texture of structures. This technique may be applied across a wide variety of clinical examinations and may not yet be completely understood and appreciated by sonographers. This review aims to educate readers on how RTAFs work, supported by examples of their benefit to image quality. In particular, the authors describe the effectiveness of using RTAF for superficial structures (thyroid, abdominal wall), deep structures (abdomen, pelvis), and dynamic examinations, including musculoskeletal and vascular applications.
Financialised Capitalism: After the Crisis and beyond Neoliberalism
Authors: Montgomerie Johnna , Williams Karel
Published: May 2009

This paper serves as an introduction to a special issue which explores many new questions, intellectual and political, posed by the current global financial crisis. The aim is to get beyond the convention asking the well-rehearsed questions about what caused the crisis, or why the established theories could not predict it. For we can safely predict that many critical thinkers in political and cultural economy already know, or think they know, the answer to what caused the crisis. This is because they will construct the origins and causes of the within the problematic which they endorsed before the crisis began. Namely, that neoliberalism demarcates the period since 1970 as one of privatisation, liberalisation and support for free markets which essentially takes ideological propositions at their own word and, consequently, fail to distinguish between rhetoric and practice. This special issue explores some new ways of fundamentally reconsidering or challenging established ideas about neoliberalism and finance. For financialisation researchers, the intellectual struggle against organising concepts of neoliberalism and disembedded finance is unfinished business.
Rethinking Neoliberalism and the Subprime Crisis: Beyond the Re-Regulation Agenda
Authors: Konings Martijn
Published: May 2009

Many critical commentators view the current crisis and the attendant legitimacy problems for free-market capitalism as an opportunity to make the case for financial re-regulation, i.e. a reassertion of public values against globalising markets. This paper suggests that such assessments of the political possibilities offered by the subprime crisis rest on a misappraisal of its nature and, more broadly, the nature of the neoliberal era. It argues that the financial expansion of the past decades cannot be adequately understood in terms of the state's failure to regulate financial markets. Financial growth has not involved the retreat of public institutions, the dissolution of social bonds or an emptying out of subjectivity, but has rather been a process whereby new organisational linkages were forged, particular norms and relations of institutional control were constructed and complex identities with thoroughly interlinked emotional households were created. Through a historical interpretation of the development of American finance since the New Deal, the paper outlines how the reconfigurations of neoliberalism have not reduced but enhanced the institutional capacities of the American state, as well as the leverage and power resources available to those who enjoy privileged access to the state's organisational mechanisms. It then returns to the question of the political significance of the current crisis, suggesting that to seize on the change in ideological climate to advocate increased state control over financial life is likely to come down to supporting the restoration and fortification of an infrastructure of financial power that we criticised when it still went under the ideological banner of neoliberalism.
Biochemical characterization of bovine plasma thrombin-activatable fibrinolysis inhibitor (TAFI)
Authors: Valnickova Zuzana , Thaysen-Andersen Morten , Højrup Peter , Christensen Trine , Sanggaard Kristian W , Kristensen Torsten , Enghild Jan J
Published: May 2009

Background

TAFI is a plasma protein assumed to be an important link between coagulation and fibrinolysis. The three-dimensional crystal structures of authentic mature bovine TAFI (TAFIa) in complex with tick carboxypeptidase inhibitor, authentic full lenght bovine plasma thrombin-activatable fibrinolysis inhibitor (TAFI), and recombinant human TAFI have recently been solved. In light of these recent advances, we have characterized authentic bovine TAFI biochemically and compared it to human TAFI.

Results

The four N-linked glycosylation sequons within the activation peptide were all occupied in bovine TAFI, similar to human TAFI, while the sequon located within the enzyme moiety of the bovine protein was non-glycosylated. The enzymatic stability and the kinetic constants of TAFIa differed somewhat between the two proteins, as did the isoelectric point of TAFI, but not TAFIa. Equivalent to human TAFI, bovine TAFI was a substrate for transglutaminases and could be proteolytically cleaved by trypsin or thrombin/solulin complex, although small differences in the fragmentation patterns were observed. Furthermore, bovine TAFI exhibited intrinsic activity and TAFIa attenuated tPA-mediated fibrinolysis similar to the human protein.

Conclusion

The findings presented here suggest that the properties of these two orthologous proteins are similar and that conclusions reached using the bovine TAFI may be extrapolated to the human protein.
Improving classification in protein structure databases using text mining
Authors: Koussounadis Antonis , Redfern Oliver C , Jones David T
Published: May 2009

Background

The classification of protein domains in the CATH resource is primarily based on structural comparisons, sequence similarity and manual analysis. One of the main bottlenecks in the processing of new entries is the evaluation of 'borderline' cases by human curators with reference to the literature, and better tools for helping both expert and non-expert users quickly identify relevant functional information from text are urgently needed. A text based method for protein classification is presented, which complements the existing sequence and structure-based approaches, especially in cases exhibiting low similarity to existing members and requiring manual intervention. The method is based on the assumption that textual similarity between sets of documents relating to proteins reflects biological function similarities and can be exploited to make classification decisions.

Results

An optimal strategy for the text comparisons was identified by using an established gold standard enzyme dataset. Filtering of the abstracts using a machine learning approach to discriminate sentences containing functional, structural and classification information that are relevant to the protein classification task improved performance. Testing this classification scheme on a dataset of 'borderline' protein domains that lack significant sequence or structure similarity to classified proteins showed that although, as expected, the structural similarity classifiers perform better on average, there is a significant benefit in incorporating text similarity in logistic regression models, indicating significant orthogonality in this additional information. Coverage was significantly increased especially at low error rates, which is important for routine classification tasks: 15.3% for the combined structure and text classifier compared to 10% for the structural classifier alone, at 10-3 error rate. Finally when only the highest scoring predictions were used to infer classification, an extra 4.2% of correct decisions were made by the combined classifier.

Conclusion

We have described a simple text based method to classify protein domains that demonstrates an improvement over existing methods. The method is unique in incorporating structural and text based classifiers directly and is particularly useful in cases where inconclusive evidence from sequence or structure similarity requires laborious manual classification.
Isolation and characterization of a spontaneously immortalized bovine retinal pigmented epithelial cell line
Authors: Liggett Thomas E , Griffiths T Daniel , Gaillard Elizabeth R
Published: May 2009

Background

The Retinal Pigmented Epithelium (RPE) is juxtaposed with the photoreceptor outer segments of the eye. The proximity of the photoreceptor cells is a prerequisite for their survival, as they depend on the RPE to remove the outer segments and are also influenced by RPE cell paracrine factors. RPE cell death can cause a progressive loss of photoreceptor function, which can diminish vision and, over time, blindness ensues. Degeneration of the retina has been shown to induce a variety of retinopathies, such as Stargardt's disease, Cone-Rod Dystrophy (CRD), Retinitis Pigmentosa (RP), Fundus Flavimaculatus (FFM), Best's disease and Age-related Macular Degeneration (AMD). We have cultured primary bovine RPE cells to gain a further understanding of the mechanisms of RPE cell death. One of the cultures, named tRPE, surpassed senescence and was further characterized to determine its viability as a model for retinal diseases.

Results

The tRPE cell line has been passaged up to 150 population doublings and was shown to be morphologically similar to primary cells. They have been characterized to be of RPE origin by reverse transcriptase PCR and immunocytochemistry using the RPE-specific genes RPE65 and CRALBP and RPE-specific proteins RPE65 and Bestrophin. The tRPE cells are also immunoreactive to vimentin, cytokeratin and zonula occludens-1 antibodies. Chromosome analysis indicates a normal diploid number. The tRPE cells do not grow in suspension or in soft agar. After 3H thymidine incorporation, the cells do not appear to divide appreciably after confluency.

Conclusion

The tRPE cells are immortal, but still exhibit contact inhibition, serum dependence, monolayer growth and secrete an extra-cellular matrix. They retain the in-vivo morphology, gene expression and cell polarity. Additionally, the cells endocytose exogenous melanin, A2E and purified lipofuscin granules. This cell line may be a useful in-vitro research model for retinal maculopathies.
Characteristics of HIV seroprevalence of visitors to public health centers under the national HIV surveillance system in Korea: cross sectional study
Authors: Kee Mee-Kyung , Lee Jin-Hee , Chu Chaeshin , Lee Eun-Ju , Kim Sung-Soon
Published: May 2009

Background

In Korea, the cumulative number of HIV-infected individuals was smaller than those of other countries. Mandatory HIV tests, dominating method until 1990's, have been gradually changed to voluntary HIV tests. We investigated HIV seroprevalence status and its characteristics of visitors to Public Health Centers (PHCs), which conducted both mandatory test and voluntary test under the national HIV/STI surveillance program.

Methods

We used HIV-testing data from 246 PHCs in 2005 through the Health Care Information System. The number of test taker was calculated using the code distinguished by the residential identification number. The subjects were classified into four groups by reason for testing; General group, HIV infection suspected group (HIV ISG), HIV test recommended group (HIV TRG), and sexually transmitted infection (STI) risk group.

Results

People living with HIV/AIDS were 149 (124 male and 25 female) among 280,456 individuals tested at PHCs. HIV seroprevalence was 5.3 per 10,000 individuals. Overall, the male revealed significantly higher seroprevalence than the female (adjusted Odds Ratio (adj. OR): 6.2; CI 3.8–10.2). Individuals aged 30–39 years (adj. OR: 2.6; CI 1.7–4.0), and 40–49 years (adj. OR: 3.8; CI 2.4–6.0) had higher seroprevalence than 20–29 years. Seroprevalence of HIV ISG (voluntary test takers and cases referred by doctors) was significantly higher than those of others. Foreigners showed higher seroprevalence than native Koreans (adj. OR: 3.8; CI 2.2–6.4). HIV ISG (adj. OR: 4.9; CI 3.2–7.5), and HIV TRG (adj. OR: 2.6; CI 1.3–5.4) had higher seroprevalence than General group.

Conclusion

A question on the efficiency of current mandatory test is raised because the seroprevalence of mandatory test takers was low. However, HIV ISG included voluntary test takers was high in our result. Therefore, we suggest that Korea needs to develop a method encouraging more people to take voluntary tests at PHCs, also to expand the anonymous testing centers and Voluntary Counselling and Testing Program (VCT) for general population to easily access to HIV testing.
Physical activity, energy requirements, and adequacy of dietary intakes of older persons in a rural Filipino community
Authors: Risonar Maria Grace D , Rayco-Solon Pura , Ribaya-Mercado Judy D , Solon Juan Antonio A , Cabalda Aegina B , Tengco Lorena W , Solon Florentino S
Published: May 2009

Background

Aging is a process associated with physiological changes such as in body composition, energy expenditure and physical activity. Data on energy and nutrient intake adequacy among elderly is important for disease prevention, health maintenance and program development.

Methods

This descriptive cross-sectional study was designed to determine the energy requirements and adequacy of energy and nutrient intakes of older persons living in private households in a rural Filipino community. Study participants were generally-healthy, ambulatory, and community living elderly aged 60–100 y (n = 98), 88 of whom provided dietary information in three nonconsecutive 24-hour food-recall interviews.

Results

There was a decrease in both physical activity and food intake with increasing years. Based on total energy expenditure and controlling for age, gender and socio-economic status, the average energy requirement for near-old (≥ 60 to < 65 y) males was 2074 kcal/d, with lower requirements, 1919 and 1699 kcal/d for the young-old (≥ 65 to < 75 y) and the old-old (≥ 75 y), respectively. Among females, the average energy requirements for the 3 age categories were 1712, 1662, and 1398 kcal/d, respectively. Actual energy intakes, however, were only ~65% adequate for all subjects as compared to energy expenditure. Protein, fat, and micronutrients (vitamins A and C, thiamin, riboflavin, iron and calcium) intakes were only ~24–51% of the recommended daily intake. Among this population, there was a weight decrease of 100 g (p = 0.012) and a BMI decrease of 0.04 kg/m2 (p = 0.003) for every 1% decrease in total caloric intake as percentage of the total energy expenditure requirements.

Conclusion

These community living elderly suffer from lack of both macronutrient intake as compared with energy requirements, and micronutrient intake as compared with the standard dietary recommendations. Their energy intakes are ~65% of the amounts required based on their total energy expenditure. Though their intakes decrease with increasing age, so do their energy expenditure, making their relative insufficiency of food intake stable with age.
Cost-effectiveness of pioglitazone in type 2 diabetes patients with a history of macrovascular disease: a German perspective
Authors: Scherbaum Werner A , Goodall Gordon , Erny-Albrecht Katrina M , Massi-Benedetti Massimo , Erdmann Erland , Valentine William J
Published: May 2009

Background

The aim of this study was to project health-economic outcomes relevant to the German setting for the addition of pioglitazone to existing treatment regimens in patients with type 2 diabetes, evidence of macrovascular disease and at high risk of cardiovascular events.

Methods

Event rates corresponding to macrovascular outcomes from the Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive) study of pioglitazone were used with a modified version of the CORE Diabetes Model to simulate outcomes over a 35-year time horizon. Direct medical costs were accounted from a healthcare payer perspective in year 2005 values. Germany specific costs were applied for patient treatment, hospitalization and management. Both costs and clinical benefits were discounted at 5.0% per annum.

Results

Over patient lifetimes pioglitazone treatment improved undiscounted life expectancy by 0.406 years and improved quality-adjusted life expectancy by 0.120 quality-adjusted life years (QALYs) compared to placebo. Direct medical costs (treatment plus complication costs) were marginally higher for pioglitazone treatment and calculation of the incremental cost-effectiveness ratio (ICER) produced a value of €13,294 per QALY gained with the pioglitazone regimen versus placebo. Acceptability curve analysis showed that there was a 78.2% likelihood that pioglitazone would be considered cost-effective in Germany, using a "good value for money" threshold of €50,000 per QALY gained. Sensitivity analyses showed that the results were most sensitive to changes in the simulation time horizon. After adjustment for the potential stabilization of pancreatic β-cell function with pioglitazone treatment, the ICER was €6,667 per QALY gained for pioglitazone versus placebo.

Conclusion

The findings of this modelling analysis indicated that, for patients with a history of macrovascular disease, addition of pioglitazone to existing therapy reduces the long-term cumulative incidence of diabetes-complications at a cost that would be considered to represent good value for money in the German setting.
F-actin-based extensions of the head cyst cell adhere to the maturing spermatids to maintain them in a tight bundle and prevent their premature release in Drosophila testis
Authors: Desai Bela S , Shirolikar Seema , Ray Krishanu
Published: May 2009

Background

In Drosophila, all the 64 clonally derived spermatocytes differentiate in syncytium inside two somatic-origin cyst cells. They elongate to form slender spermatids, which are individualized and then released into the seminal vesicle. During individualization, differentiating spermatids are organized in a tight bundle inside the cyst, which is expected to play an important role in sperm selection. However, actual significance of this process and its underlying mechanism are unclear.

Results

We show that dynamic F-actin-based processes extend from the head cyst cell at the start of individualization, filling the interstitial space at the rostral ends of the maturing spermatid bundle. In addition to actin, these structures contained lamin, beta-catenin, dynamin, myosin VI and several other filopodial components. Further, pharmacological and genetic analyses showed that cytoskeletal stability and dynamin function are essential for their maintenance. Disruption of these F-actin based processes was associated with spermatid bundle disassembly and premature sperm release inside the testis.

Conclusion

Altogether, our data suggests that the head cyst cell adheres to the maturing spermatid heads through F-actin-based extensions, thus maintaining them in a tight bundle. This is likely to regulate mature sperm release into the seminal vesicle. Overall, this process bears resemblance to mammalian spermiation.
Detection and phylogenetic analysis of Orf virus from sheep in Brazil: a case report
Authors: Abrahão Jônatas S , Campos Rafael K , Trindade Giliane S , Guedes Maria IM , Lobato Zélia IP , Mazur Carlos , Ferreira Paulo CP , Bonjardim Cláudio A , Kroon Erna G
Published: May 2009

Background

Orf virus (ORFV), the prototype of the genus Parapoxvirus (PPV), is the etiological agent of contagious ecthyma, a severe exanthematic dermatitis that afflicts domestic and wild small ruminants. Although South American ORFV outbreaks have occurred and diagnosed there are no South American PPV major membrane glycoprotein B2L gene nucleotide sequences available.

Case presentation

an outbreak of ovine contagious ecthyma in Midwest Brazil was investigated. The diagnosis was based on clinical examinations and molecular biology techniques. The molecular characterization of the virus was done using PCR amplification, cloning and DNA sequencing of the B2L gene. The phylogenetic analysis demonstrated a high degree of identity with ORFV strains, and the isolate was closest to the ORFV-India 82/04 isolate. Another Brazilian ORFV isolate, NE1, was sequenced for comparative analysis and also showed a high degree of identity with an Asian ORFV strain.

Conclusion

Distinct ORFV strains are circulating in Brazil. This is the first report on the phylogenetic analysis of an ORFV in South America.
Genetic and environmental pathways to complex diseases
Authors: Gohlke Julia M , Thomas Reuben , Zhang Yonqing , Rosenstein Michael C , Davis Allan P , Murphy Cynthia , Becker Kevin G , Mattingly Carolyn J , Portier Christopher J
Published: May 2009

Background

Pathogenesis of complex diseases involves the integration of genetic and environmental factors over time, making it particularly difficult to tease apart relationships between phenotype, genotype, and environmental factors using traditional experimental approaches.

Results

Using gene-centered databases, we have developed a network of complex diseases and environmental factors through the identification of key molecular pathways associated with both genetic and environmental contributions. Comparison with known chemical disease relationships and analysis of transcriptional regulation from gene expression datasets for several environmental factors and phenotypes clustered in a metabolic syndrome and neuropsychiatric subnetwork supports our network hypotheses. This analysis identifies natural and synthetic retinoids, antipsychotic medications, Omega 3 fatty acids, and pyrethroid pesticides as potential environmental modulators of metabolic syndrome phenotypes through PPAR and adipocytokine signaling and organophosphate pesticides as potential environmental modulators of neuropsychiatric phenotypes.

Conclusion

Identification of key regulatory pathways that integrate genetic and environmental modulators define disease associated targets that will allow for efficient screening of large numbers of environmental factors, screening that could set priorities for further research and guide public health decisions.
Enhanced reactivity to pain in patients with rheumatoid arthritis
Authors: Edwards Robert R , Wasan Ajay D , Bingham Clifton O , Bathon Joan , Haythornthwaite Jennifer A , Smith Michael T , Page Gayle G
Published: May 2009

Introduction

Maladaptive physiological responses to stress appear to play a role in chronic inflammatory diseases such as rheumatoid arthritis (RA). However, relatively little stress research in RA patients has involved the study of pain, the most commonly reported and most impairing stressor in RA. In the present study, we compared psychophysical and physiological responses to standardized noxious stimulation in 19 RA patients and 21 healthy controls.

Methods

Participants underwent a single psychophysical testing session in which responses to a variety of painful stimuli were recorded, and blood samples were taken at multiple time points to evaluate the reactivity of cortisol, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) to the experience of acute pain.

Results

The findings suggest that RA patients display a fairly general hyperalgesia to mechanical and thermal stimuli across several body sites. In addition, while serum cortisol levels did not differ at baseline or following pain testing in patients relative to controls, the RA patients tended to show elevations in serum IL-6 and demonstrated enhanced pain-reactivity of serum levels of TNF-α compared with the healthy controls (P < 0.05).

Conclusions

These findings highlight the importance of pain as a stressor in RA patients and add to a small body of literature documenting amplified responses to pain in RA. Future studies of the pathophysiology of RA would benefit from the consideration of acute pain levels when comparing RA patients with other groups, and future trials of analgesic interventions in RA patients may benefit from evaluating the effects of such interventions on inflammatory activity.
Long-term survival of chronic dialysis patients following survival from an episode of multiple-organ failure
Authors: Chapman Richard J , Templeton Maie , Ashworth Simon , Broomhead Robert , McLean Adam , Brett Stephen J
Published: May 2009

Introduction

This study aimed to examine the long-term outcome for patients with end-stage renal failure (ESRF) who survived multiple-organ failure.

Methods

We performed a review of databases from the renal medicine service and intensive care units (ICU) of the participating hospitals within Imperial College Healthcare NHS Trust, London, UK. Patients with ESRF admitted to ICU who required support of two or more organ systems or were ventilated for more than 36 hours were included. To provide a comparison we examined the survival of a comparator group of ESRF patients in the general population with similar demographic and disease characteristics to our study group. We also examined the outcome for ESRF patients admitted to ICU who died prior to discharge.

Results

Survival data for two years following discharge from ICU were examined for the impact of age, prior dialysis history, Acute Physiology and Chronic Health Evaluation (APACHE) II scores and medical or surgical status. Of the 199 patients who met the inclusion criteria, 111 (56%) survived their ICU stay. Sixty-two (56%) of the survivors remained alive two years following discharge. There was no group difference in survival with regards to age, dialysis history or APACHE II scores. Those admitted with a medical rather than surgical diagnosis were less likely to survive two years (P < 0.01). Patients who died in ICU had higher APACHE II scores (P < 0.0001) and were more likely to have a medical diagnosis. By log rank analysis two-year mortality was significantly higher (P = 0.003) in the ICU survivors than the comparator group with ESRF. This difference was lost when patients who died within a month of discharge were excluded.

Conclusions

ESRF patients with multiple-organ failure have a high mortality, with the increased risk of death continuing into the early post-ICU period. Those with non-surgical diagnoses have the highest risk. Survival within the group who live beyond the early post-ICU period appears similar to the background population of ESRF patients.
Evaluation of the Optimal Number of Lesions Needed for Tumor Evaluation Using the Response Evaluation Criteria in Solid Tumors: A North Central Cancer Treatment Group Investigation
Authors: Hillman Shauna L. , An Ming-Wen , O'Connell Michael J. , Goldberg Richard M. , Schaefer Paul , Buckner Jan C. , Sargent Daniel J.
Published: May 2009

Purpose

In February 2000, the criteria for measuring tumor shrinkage as an indicator of antitumor activity were redefined by the Response Evaluation Criteria in Solid Tumors (RECIST). This resulted in simplifying bidimensional to unidimensional measurement of lesions. Under RECIST, all lesions, up to 10, must be measured. Scanning and measuring multiple lesions is costly, time-consuming, and a disincentive to participation in clinical trials. We investigated whether fewer than 10 lesions can be measured without compromising the accuracy of assessing a regimen's activity.

Patients and Methods

Thirty-two North Central Cancer Treatment Group trials including 2,374 patients were analyzed. Twelve studies were conducted before RECIST; 20 were conducted post-RECIST. Agreement between objective status by cycle, confirmed response, overall response rate, and time to progression (TTP) was evaluated based on all 10 versus the largest one through five lesions.

Results

The median number of lesions reported on RECIST trials did not differ from pre-RECIST trials (median = 2.0). One lesion at baseline was reported in 49% of patients, two lesions in 28% of patients, three lesions in 12% of patients, four lesions in 6% of patients, and five lesions in 5% of patients in post-RECIST trials. Utilizing the largest two lesions produced excellent concordance with that using all lesions for all end points. In no trial did the overall response rate differ by more than 3% when two versus all lesions were considered. Evaluating more than two lesions did not significantly improve agreement.

Conclusion

Based on these trials, the assessment of more than two lesions did not alter the conclusions regarding a treatment's efficacy as judged by response rate or TTP.
Inlet flow conditions and the jet impact work in a Pelton turbine
Authors: Zhang Zh
Published: May 2009

The inlet flow of the jet entering the rotating buckets of a Pelton wheel turbine is considered with respect to jet flow impact and the non-disturbing flow condition. In the first step the volume rate of flow in the rotating frame of reference is shown to be independent of the bucket rotational position. Next, kinematical distinctions are made between the inlet flow at the bucket cut-out and inlet flow at the bucket splitter. Then, based on calculations of the impact forces and the corresponding impact work, the percentage of total jet impact energy is estimated. For purposes of configuring the proper inlet flow, the non-disturbing flow condition is specified and the corresponding criterion for geometry layout of the bucket is shown to be a function of the Pelton wheel turbine specific speed.
Analytical method for frictional flows in a Pelton turbine
Authors: Zhang Zh
Published: May 2009

The frictional flow in the rotating buckets of a Pelton turbine has been considered analytically for two special cases: the lateral flow along the path of constant circumferential velocity and the longitudinal flow with varying circumferential velocity. For the first flow form, the additional concept regarding the flow losses and dissipation in the flow has been accounted for to complete the existing flow friction theorem. For the longitudinal flow in the rotating buckets, detailed analyses have been performed to confirm the influences of centrifugal, Coriolis, frictional, and inertia forces on the power exchange between water and rotating buckets. Because the flow of this form along the bucket surface could not be integrated mathematically, the calculation algorithm by means of the spreadsheet method has been presented. For both flow forms, the flow friction has again been confirmed to be most effective in affecting the hydraulic efficiency. Because the flow mechanism in the rotating buckets of a Pelton turbine has been extensively worked out, direct calculations of combined flows of other forms become highly available, for instance in using the spreadsheet, and can be considered at least as a best available alternative to the computational fluid dynamics.
Flow dynamics of the free surface flow in the rotating buckets of a Pelton turbine
Authors: Zhang Zh
Published: May 2009

The relative flow in the rotating buckets of a Pelton turbine was calculated with respect to the influences of centrifugal, Coriolis, and impact forces. Based on the assumption of frictionless flows, the so-called invariance equation was presented, which enables the changeable flow velocity in a rotating bucket to be calculated. The introduced jet layer method relying on the invariance equation significantly simplifies the computation of the entire jet expansion in the rotating bucket. For purely radial flows, contributions of centrifugal, Coriolis, and impact forces to the power exchange and the corresponding effectiveness relations were quantified. In general, the centrifugal force only performs the negligible work, if compared with the effectiveness of the Coriolis and the impact forces. Various calculation examples were presented to show the flow development and the effectiveness of all active forces in the rotating bucket and to explain the application of the invariance equation. The results presented in the article for frictionless flows can be applied as the reference for further computational and experimental investigations with respect to the flow friction effects on the hydraulic efficiency of a Pelton turbine.