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Design and implementation of a high-performance CCA event service,CONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 9 2009
Abstract Event services based on publish,subscribe architectures are well-established components of distributed computing applications. Recently, an event service has been proposed as part of the common component architecture (CCA) for high-performance computing (HPC) applications. In this paper we describe our implementation, experimental evaluation, and initial experience with a high-performance CCA event service that exploits efficient communications mechanisms commonly used on HPC platforms. We describe the CCA event service model and briefly discuss the possible implementation strategies of the model. We then present the design and implementation of the event service using the aggregate remote memory copy interface as an underlying communication layer for this mechanism. Two alternative implementations are presented and evaluated on a Cray XD-1 platform. The performance results demonstrate that event delivery latencies are low and that the event service is able to achieve high-throughput levels. Finally, we describe the use of the event service in an application for high-speed processing of data from a mass spectrometer and conclude by discussing some possible extensions to the event service for other HPC applications. Published in 2009 by John Wiley & Sons, Ltd. [source]
Reliability in grid computing systems,CONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 8 2009
Abstract In recent years, grid technology has emerged as an important tool for solving compute-intensive problems within the scientific community and in industry. To further the development and adoption of this technology, researchers and practitioners from different disciplines have collaborated to produce standard specifications for implementing large-scale, interoperable grid systems. The focus of this activity has been the Open Grid Forum, but other standards development organizations have also produced specifications that are used in grid systems. To date, these specifications have provided the basis for a growing number of operational grid systems used in scientific and industrial applications. However, if the growth of grid technology is to continue, it will be important that grid systems also provide high reliability. In particular, it will be critical to ensure that grid systems are reliable as they continue to grow in scale, exhibit greater dynamism, and become more heterogeneous in composition. Ensuring grid system reliability in turn requires that the specifications used to build these systems fully support reliable grid services. This study surveys work on grid reliability that has been done in recent years and reviews progress made toward achieving these goals. The survey identifies important issues and problems that researchers are working to overcome in order to develop reliability methods for large-scale, heterogeneous, dynamic environments. The survey also illuminates reliability issues relating to standard specifications used in grid systems, identifying existing specifications that may need to be evolved and areas where new specifications are needed to better support the reliability. Published in 2009 by John Wiley & Sons, Ltd. [source]
Usability levels for sparse linear algebra components,CONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 12 2008
Abstract Sparse matrix computations are ubiquitous in high-performance computing applications and often are their most computationally intensive part. In particular, efficient solution of large-scale linear systems may drastically improve the overall application performance. Thus, the choice and implementation of the linear system solver are of paramount importance. It is difficult, however, to navigate through a multitude of available solver packages and to tune their performance to the problem at hand, mainly because of the plethora of interfaces, each requiring application adaptations to match the specifics of solver packages. For example, different ways of setting parameters and a variety of sparse matrix formats hinder smooth interactions of sparse matrix computations with user applications. In this paper, interfaces designed for components that encapsulate sparse matrix computations are discussed in the light of their matching with application usability requirements. Consequently, we distinguish three levels of interfaces, high, medium, and low, corresponding to the degree of user involvement in the linear system solution process and in sparse matrix manipulations. We demonstrate when each interface design choice is applicable and how it may be used to further users' scientific goals. Component computational overheads caused by various design choices are also examined, ranging from low level, for matrix manipulation components, to high level, in which a single component contains the entire linear system solver. Published in 2007 by John Wiley & Sons, Ltd. [source]
APEX-Map: a parameterized scalable memory access probe for high-performance computing systems,CONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 17 2007
Abstract The memory wall between the peak performance of microprocessors and their memory performance has become the prominent performance bottleneck for many scientific application codes. New benchmarks measuring data access speeds locally and globally in a variety of different ways are needed to explore the ever increasing diversity of architectures for high-performance computing. In this paper, we introduce a novel benchmark, APEX-Map, which focuses on global data movement and measures how fast global data can be fed into computational units. APEX-Map is a parameterized, synthetic performance probe and integrates concepts for temporal and spatial locality into its design. Our first parallel implementation in MPI and various results obtained with it are discussed in detail. By measuring the APEX-Map performance with parameter sweeps for a whole range of temporal and spatial localities performance surfaces can be generated. These surfaces are ideally suited to study the characteristics of the computational platforms and are useful for performance comparison. Results on a global-memory vector platform and distributed-memory superscalar platforms clearly reflect the design differences between these different architectures. Published in 2007 by John Wiley & Sons, Ltd. [source]
Developing LHCb Grid software: experiences and advancesCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 2 2007
Abstract The LHCb Grid software has been used for two Physics Data Challenges, with the latter producing over 98 TB of data and consuming over 650 processor-years of computing power. This paper discusses the experience of developing a Grid infrastructure, interfacing to an existing Grid (LCG) and traditional computing centres simultaneously, running LHCb experiment software and jobs on the Grid, and the integration of a number of new technologies into the Grid infrastructure. Our experience and utilization of the following core technologies will be discussed: OGSI, XML-RPC, Grid services, LCG middleware and instant messaging. Specific attention will be given to analysing the behaviour of over 100,000 jobs executed through the LCG Grid environment, providing insight into the performance, failure modes and scheduling efficiency over a period of several months for a large computational Grid incorporating over 40 sites and thousands of nodes. © Crown copyright 2006. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd. [source]
A performance comparison between the Earth Simulator and other terascale systems on a characteristic ASCI workload,CONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 10 2005
Darren J. Kerbyson
Abstract This work gives a detailed analysis of the relative performance of the recently installed Earth Simulator and the next top four systems in the Top500 list using predictive performance models. The Earth Simulator uses vector processing nodes interconnected using a single-stage, cross-bar network, whereas the next top four systems are built using commodity based superscalar microprocessors and interconnection networks. The performance that can be achieved results from an interplay of system characteristics, application requirements and scalability behavior. Detailed performance models are used here to predict the performance of two codes representative of the ASCI workload, namely SAGE and Sweep3D. The performance models encapsulate fully the behavior of these codes and have been previously validated on many large-scale systems. One result of this analysis is to size systems, built from the same nodes and networks as those in the top five, that will have the same performance as the Earth Simulator. In particular, the largest ASCI machine, ASCI Q, is expected to achieve a similar performance to the Earth Simulator on the representative workload. Published in 2005 by John Wiley & Sons, Ltd. [source]
Evaluating high-performance computers,CONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 10 2005
Jeffrey S. Vetter
Abstract Comparisons of high-performance computers based on their peak floating point performance are common but seldom useful when comparing performance on real workloads. Factors that influence sustained performance extend beyond a system's floating-point units, and real applications exercise machines in complex and diverse ways. Even when it is possible to compare systems based on their performance, other considerations affect which machine is best for a given organization. These include the cost, the facilities requirements (power, floorspace, etc.), the programming model, the existing code base, and so on. This paper describes some of the important measures for evaluating high-performance computers. We present data for many of these metrics based on our experience at Lawrence Livermore National Laboratory (LLNL), and we compare them with published information on the Earth Simulator. We argue that evaluating systems involves far more than comparing benchmarks and acquisition costs. We show that evaluating systems often involves complex choices among a variety of factors that influence the value of a supercomputer to an organization, and that the high-end computing community should view cost/performance comparisons of different architectures with skepticism. Published in 2005 by John Wiley & Sons, Ltd. [source]
The ASCI Computational Grid: initial deploymentCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 13-15 2002
Abstract Grid Services, a Department of Energy Accelerated Strategic Computing Initiative program, has designed, implemented, and deployed a grid-based solution for customer access to large computing resources at DOE weapons labs and plants. Customers can access and monitor diverse, geographically distributed resources using the common Grid Services interfaces. This paper discusses the architecture, security, and user interfaces of the Grid Services infrastructure. Published in 2002 by John Wiley & Sons, Ltd. [source]
The epidemiology of contact allergy in the general population , prevalence and main findingsCONTACT DERMATITIS, Issue 5 2007
Jacob Pontoppidan Thyssen
A substantial number of studies have investigated the prevalence of contact allergy in the general population and in unselected subgroups of the general population. The aim of this review was to determine a median prevalence and summarize the main findings from studies on contact allergy in the general population. Published research mainly originates from North America and Western Europe. The median prevalence of contact allergy to at least 1 allergen was 21.2% (range 12.5,40.6%), and the weighted average prevalence was 19.5%, based on data collected on all age groups and all countries between 1966 and 2007. The most prevalent contact allergens were nickel, thimerosal, and fragrance mix. The median nickel allergy prevalence was 8.6% (range 0.7,27.8%) and demonstrates that nickel was an important cause of contact allergy in the general population and that it was widespread in both men and women. Numerous studies demonstrated that pierced ears were a significant risk factor for nickel allergy. Nickel was a risk factor for hand eczema in women. Finally, heavy smoking was associated with contact allergy, mostly in women. Population-based epidemiological studies are considered a prerequisite in the surveillance of national and international contact allergy epidemics. [source]
Manganese cell labeling of murine hepatocytes using manganese(III)-transferrin,CONTRAST MEDIA & MOLECULAR IMAGING, Issue 3 2008
Christopher H. Sotak
Abstract Manganese(III)-transferrin [Mn(III),Tf] was investigated as a way to accomplish manganese-labeling of murine hepatocytes for MRI contrast. It is postulated that Mn(III),Tf can exploit the same transferrin-receptor-dependent and -independent metabolic pathways used by hepatocytes to transport the iron analog Fe(III),Tf. More specifically, it was investigated whether manganese delivered by transferrin could give MRI contrast in hepatocytes. Comparison of the T1 and T2 relaxation times of Mn(III),Tf and Fe(III),Tf over the same concentration range showed that the r1 relaxivities of the two metalloproteins are the same in vitro, with little contribution from paramagnetic enhancement. The degree of manganese cell labeling following incubation for 2,7,h in 31.5,µm Mn(III),Tf was comparable to that of hepatocytes incubated in 500,µm Mn2+ for 1,h. The intrinsic manganese tissue relaxivity between Mn(III),Tf-labeled and Mn2+ -labeled cells was found to be the same, consistent with Mn(III) being released from transferrin and reduced to Mn2+. For both treatment regimens, manganese uptake by hepatocytes appeared to saturate in the first 1,2,h of the incubation period and may explain why the efficiency of hepatocyte cell labeling by the two methods appeared to be comparable in spite of the ,16-fold difference in effective manganese concentration. Hepatocytes continuously released manganese, as detected by MRI, and this was the same for both Mn2+ - and Mn(III),Tf-labeled cells. Manganese release may be the result of normal hepatocyte function, much in the same way that hepatocytes excrete manganese into the bile in vivo. This approach exploits a biological process,namely receptor binding, endocytosis and endosomal acidification,to initiate the release of an MRI contrast agent, potentially conferring more specificity to the labeling process. The ubiquitous expression of transferrin receptors by eukaryotic cells should make Mn(III),Tf particularly useful for manganese labeling of a wide variety of cells both in culture and in vivo. Published in 2008 by John Wiley & Sons, Ltd. [source]
Imaging of the lymphatic system: new horizons,CONTRAST MEDIA & MOLECULAR IMAGING, Issue 6 2006
Abstract The lymphatic system is a complex network of lymph vessels, lymphatic organs and lymph nodes. Traditionally, imaging of the lymphatic system has been based on conventional imaging methods like computed tomography (CT) and magnetic resonance imaging (MRI), whereby enlargement of lymph nodes is considered the primary diagnostic criterion for disease. This is particularly true in oncology, where nodal enlargement can be indicative of nodal metastases or lymphoma. CT and MRI on their own are, however, anatomical imaging methods. Newer imaging methods such as positron emission tomography (PET), dynamic contrast-enhanced MRI (DCE-MRI) and color Doppler ultrasound (CDUS) provide a functional assessment of node status. None of these techniques is capable of detecting flow within the lymphatics and, thus, several intra-lymphatic imaging methods have been developed. Direct lymphangiography is an all-but-extinct method of visualizing the lymphatic drainage from an extremity using oil-based iodine contrast agents. More recently, interstitially injected intra-lymphatic imaging, such as lymphoscintigraphy, has been used for lymphedema assessment and sentinel node detection. Nevertheless, radionuclide-based imaging has the disadvantage of poor resolution. This has lead to the development of novel systemic and interstitial imaging techniques which are minimally invasive and have the potential to provide both structural and functional information; this is a particular advantage for cancer imaging, where anatomical depiction alone often provides insufficient information. At present the respective role each modality plays remains to be determined. Indeed, multi-modal imaging may be more appropriate for certain lymphatic disorders. The field of lymphatic imaging is ever evolving, and technological advances, combined with the development of new contrast agents, continue to improve diagnostic accuracy. Published in 2006 by John Wiley & Sons, Ltd. [source]
Monoclonal B cell lymphocytosis: Clinical and population perspectives,CYTOMETRY, Issue S1 2010
Neil E. Caporaso
Abstract Monoclonal B Cell Lymphocytosis (MBL) refers to clones of CLL-like cells that exhibit CLL characteristics that fall short of the numbers required for CLL diagnosis. Data from large CLL kindreds document increased prevalence of MBL suggesting a genetic contribution to its etiology. The molecular features that favor progression of MBL to CLL are poorly understood but an elevated B-cell count is a risk factor for progression. An important consideration when evaluating volunteers from CLL families who are willing to donate bone marrow is that MBL be ruled out since the MBL donor clone could result in a second CLL in the recipient. Further studies of MBL are needed to identify the molecular features and how they evolve during progression. Published 2010 Wiley-Liss, Inc. [source]
CD146+ T lymphocytes are increased in both the peripheral circulation and in the synovial effusions of patients with various musculoskeletal diseases and display pro-inflammatory gene profiles,,CYTOMETRY, Issue 2 2010
Pradeep Kumar Dagur
Abstract Twenty-eight synovial effusions (SE) were obtained from 24 patients, paired samples of peripheral blood (PB) from 10 of these patients, and PB from 36 healthy individuals for analysis of CD146 on T-lymphocytes by flow cytometry. CD146+ or CD146, T-lymphocytes were sorted from three SE to study gene expression profiles and selected genes revalidated using QPCR assays. We found more CD3+CD146+ and CD4+CD146+ T-lymphocytes in PB from patients compared with PB of healthy individuals (4.71% ± 2.48% vs. 2.53% ± 1.08%, P = 0.028) and (6.29% ± 2.74% vs. 2.41% ± 0.96%, P = 0.0017), respectively, whereas CD8+CD146+ T-lymphocytes were not significantly different (2.55% ± 1.65% vs. 3.18% ± 2.59%, P = 0.5008). SE displayed CD146 staining on 16.32% ± 6.06% of CD3+ cells. This expression was skewed toward CD4+ T-lymphocytes, with CD146 present on 24.06% ± 8.20% of the CD4+ T-lymphocytes compared with 6.19% ± 5.22% of the CD8+ T-lymphocytes. CD146 on CD3+, CD4+ and CD8+ T-lymphocytes in SE was significantly higher compared with PB in patients (P < 0.0001, P < 0.0001 and P = 0.0036, respectively). Gene expression profiles of sorted CD146+CD4+CD3+ vs. CD146,CD4+CD3+ T-lymphocytes (n = 2) and CD2+CD146+ vs. CD2+CD 146, (n = 1) from SE, displayed increased CD146, LAIR2, CXCL13, CD109, IL6ST, IL6R, TNFRsf18, and TNFRsf4 genes, whereas decreased CCR7, CCL5, and cytotoxicity-associated genes including granzymes b, h, and k, perforin were found with the CD146, T-lymphocytes. By QPCR higher mRNA expression of CXCL13, CD146 and CD109 was also noted in the CD146+ subset, compared with the CD146, subset, in PB of healthy individuals and in PB and SE from patients. Our study establishes increased CD146+ T-lymphocytes in diseases with joint effusions, and demonstrates pro-inflammatory gene profiles in these cells. Published 2009 Wiley-Liss, Inc. [source]
Discrepancy in measuring CD4 expression on T-lymphocytes using fluorescein conjugates in comparison with unimolar CD4-phycoerythrin conjugates,,CYTOMETRY, Issue 6 2007
Abstract Background: Numerous methods for quantitative fluorescence calibration (QFC) have been developed to quantify receptor expression on lymphocytes. However, the results from the use of these different QFC methods vary considerably in the literature. To better identify the causes of these discrepancies, we measured CD4 expression using FITC and phycoerythrin (PE) conjugates to stain CYTO-TROLÔ Control Cells and T-lymphocytes in whole blood and isolated cell preparations. We further examined pH of the cellular microenvironment as a cause of discordant results obtained with the FITC conjugate. Methods: Calibration with Quantibrite PE-labeled microspheres and the use of unimolar CD4-PE conjugates provided direct measurement of the antibody bound per cell value (ABC) for CD4 expression on normal T-lymphocytes. Calibration for CD4-FITC monoclonal antibody (Mab) labeled CYTO-TROL Control Cells and normal T-lymphocytes was based on molecules of equivalent soluble fluorochrome (MESF) as determined by FITC-labeled microspheres traceable to NIST RM 8640. The MESF value for CD4-FITC Mab was determined that enabled the conversion of the MESF values obtained for CYTO-TROL cells to ABC. We investigated the likely pH change in the fluorescein microenvironments within FITC-labeled Mab and cells stained with FITC-labeled Mab using a pH sensitive indicator. Results: The mean ABC value for T-lymphocytes prepared from fresh whole blood using CD4-PE conjugate (48,321) was consistent with previous results, and it was much higher than the mean ABC using CD4-FITC Mab (22,156). The mean ABC value for CYTO-TROL cells using CD4-PE conjugate (43,090) was also higher than that using CD4-FITC conjugate (34,734), although the discrepancy was not as great. Further studies suggested the discrepancy in CYTO-TROL results may be accounted for by the low pH of the membrane microenvironment, but the greater discrepancy in T-lymphocytes could not be fully explained. Conclusion: CD4 expression on fresh normal whole blood samples and CYTO-TROL cells can be consistently quantified in ABC units using Quantibrite PE quantification beads and unimolar CD4-PE conjugates. Quantification with CD4-FITC conjugate is not as consistent, but may be improved by the use of CD4 T-cells as biological calibrators. This approximation is valid only for surface receptors with consensus ABC values measured by different QFC methods serving as biological standards. Published 2007 Wiley-Liss, Inc. [source]
Albumin enhanced morphometric image analysis in CLL,CYTOMETRY, Issue 1 2004
Matthew A. Lunning
Abstract BACKGROUND The heterogeneity of lymphocytes from patients with chronic lymphocytic leukemia (CLL) and blood film artifacts make morphologic subclassification of this disease difficult. METHODS We reviewed paired blood films prepared from ethylene-diamine-tetraacetic acid (ETDA) samples with and without bovine serum albumin (BSA) from 82 CLL patients. Group 1 adhered to NCCLS specifications for the preparations of EDTA blood films. Group 2 consisted of blood films containing EDTA and a 1:12 dilution of 22% BSA. Eight patients were selected for digital photomicroscopy and statistical analysis. Approximately 100 lymphocytes from each slide were digitally captured. RESULTS The mean cell area ± standard error was 127.8 ,m2 ± 1.42 for (n = 793) for group 1 versus 100.7 ,m2 ± 1.39 (n = 831) for group 2. The nuclear area was 88.9 ,m2 ± 0.85 for group 1 versus 76.4 ,m2 ± 0.83 for group 2. For the nuclear transmittance, the values were 97.6 ± 0.85 for group 1 and 104.1 ± 0.83 for group 2. The nuclear:cytoplasmic ratios were 0.71 ± 0.003 for group 1 and 0.78 ± 0.003 for group 2. All differences were statistically significant (P < 0.001). CONCLUSIONS BSA addition results in the reduction of atypical lymphocytes and a decrease in smudge cells. BSA also decreases the lymphocyte area and nuclear area, whereas nuclear transmittance and nuclear:cytoplasmic ratio are increased. A standardized method of slide preparation would allow accurate interlaboratory comparison. The use of BSA may permit better implementation of the blood film-based subclassification of CLL and lead to a better correlation of morphology with cytogenetics and immunophenotyping. Published 2003 Wiley-Liss, Inc. [source]
Human B cells express a CD45 isoform that is similar to murine B220 and is downregulated with acquisition of the memory B-cell marker CD27,CYTOMETRY, Issue 1 2003
Jack J. H. Bleesing
Abstract Background Differences between human and murine B cells exist at all stages of B-cell development, including the stage of memory B-cell formation. B cells in mice are identified with the pan,B-cell,specific CD45 isoform, B220. In initial studies in humans, it appeared that B220 expression did not include all B cells. This study was performed to expand on those preliminary findings. Methods Multiparameter flow cytometric detection of B220 expression on B cells was combined with a variety of B-cell markers. Results In contrast to mice, B220 was not a pan,B-cell marker in humans but was downregulated in the majority of B cells that acquired the human memory B-cell marker, CD27, whereas a minor memory B-cell subset remained B220+, suggesting differences in differentiation. Conclusions The B220 isoform in humans is developmentally regulated in humans, tied to the acquisition of a memory phenotype, and as such can be used as a differentiation-specific CD45 isoform, akin to the use of CD45 isoforms to distinguish between naive and memory T-cell subsets. Patients with immunodeficiency disorders, associated with defective memory B-cell generation and absent or reduced CD27+ B cells, showed a corresponding lack of B220 downregulation consistent with altered differentiation of B-cell subsets. Cytometry Part B (Clin. Cytometry) 51B:1,8, 2003. Published 2002 Wiley-Liss, Inc. [source]
Report from a workshop on multianalyte microsphere assays,,§CYTOMETRY, Issue 5 2002
Marie C. Earley
Abstract Multiplexed assays using fluorescent microspheres is an exciting technique that has been gaining popularity among researchers, particularly those in the public health field. Part of its popularity is due to its flexibility, as both immunoassays and oligonucleotide hybridization assays can be developed on this platform. This report summarizes a workshop held by the Centers for Disease Control and Prevention that discussed issues surrounding these assays and the Luminex 100 xMAP instrument. Topics included instrumentation, assay design, sample matrix and volume, quality control, and development of commercial applications. Cytometry (Clin. Cytometry) 50:239,242, 2002. Published 2002 Wiley-Liss, Inc. [source]
Expression and alternative splicing of N-RAP during mouse skeletal muscle development,CYTOSKELETON, Issue 12 2008
Abstract N-RAP alternative splicing and protein localization were studied in developing skeletal muscle tissue from pre- and postnatal mice and in fusing primary myotubes in culture. Messages encoding N-RAP-s and N-RAP-c, the predominant isoforms of N-RAP detected in adult skeletal muscle and heart, respectively, were present in a 5:1 ratio in skeletal muscle isolated from E16.5 embryos. N-RAP-s mRNA levels increased three-fold over the first 3 weeks of postnatal development, while N-RAP-c mRNA levels remained low. N-RAP alternative splicing during myotube differentiation in culture was similar to the pattern observed in embryonic and neonatal muscle, with N-RAP-s expression increasing and N-RAP-c mRNA levels remaining low. In both developing skeletal muscle and cultured myotubes, N-RAP protein was primarily associated with developing myofibrillar structures containing ,-actinin, but was not present in mature myofibrils. The results establish that N-RAP-s is the predominant spliced form of N-RAP present throughout skeletal muscle development. Cell Motil. Cytoskeleton 2008. Published 2008 Wiley-Liss, Inc. [source]
Dynamic compartmentalization of protein tyrosine phosphatase receptor Q at the proximal end of stereocilia: Implication of myosin VI-based transportCYTOSKELETON, Issue 7 2008
Abstract Hair cell stereocilia are apical membrane protrusions filled with uniformly polarized actin filament bundles. Protein tyrosine phosphatase receptor Q (PTPRQ), a membrane protein with extracellular fibronectin repeats has been shown to localize at the stereocilia base and the apical hair cell surface, and to be essential for stereocilia integrity. We analyzed the distribution of PTPRQ and a possible mechanism for its compartmentalization. Using immunofluorescence we demonstrate that PTPRQ is compartmentalized at the stereocilia base with a decaying gradient from base to apex. This distribution can be explained by a model of transport directed toward the stereocilia base, which counteracts diffusion of the molecules. By mathematical analysis, we show that this counter transport is consistent with the minus end-directed movement of myosin VI along the stereocilia actin filaments. Myosin VI is localized at the stereocilia base, and exogenously expressed myosin VI and PTPRQ colocalize in the perinuclear endosomes in COS-7 cells. In myosin VI-deficient mice, PTPRQ is distributed along the entire stereocilia. PTPRQ-deficient mice show a pattern of stereocilia disruption that is similar to that reported in myosin VI-deficient mice, where the predominant features are loss of tapered base, and fusion of adjacent stereocilia. Thin section and freeze-etching electron microscopy showed that localization of PTPRQ coincides with the presence of a dense cell surface coat. Our results suggest that PTPRQ and myosin VI form a complex that dynamically maintains the organization of the cell surface coat at the stereocilia base and helps maintain the structure of the overall stereocilia bundle. Cell Motil. Cytoskeleton 2008. Published 2008 Wiley-Liss, Inc. [source]
Diversity of effective treatments of panic attacks: what do they have in common?,DEPRESSION AND ANXIETY, Issue 1 2010
Walton T. Roth M.D.
Abstract By comparing efficacious psychological therapies of different kinds, inferences about common effective treatment mechanisms can be made. We selected six therapies for review on the basis of the diversity of their theoretical rationales and evidence for superior efficacy: psychoanalytic psychotherapy, hypercapnic breathing training, hypocapnic breathing training, reprocessing with and without eye-movement desensitization, muscle relaxation, and cognitive behavior therapy. The likely common element of all these therapies is that they reduce the immediate expectancy of a panic attack, disrupting the vicious circle of fearing fear. Modifying expectation is usually regarded as a placebo mechanism in psychotherapy, but may be a specific treatment mechanism for panic. The fact that this is seldom the rationale communicated to the patient creates a moral dilemma: Is it ethical for therapists to mislead patients to help them? Pragmatic justification of a successful practice is a way out of this dilemma. Therapies should be evaluated that deal with expectations directly by promoting positive thinking or by fostering non-expectancy. Depression and Anxiety, 2010. Published 2009 Wiley-Liss, Inc. [source]
Lifetime comorbidities between phobic disorders and major depression in Japan: results from the World Mental Health Japan 2002,2004 Survey,DEPRESSION AND ANXIETY, Issue 10 2009
Masao Tsuchiya M.A.
Abstract Background: Although often considered of minor significance in themselves, evidence exists that early-onset phobic disorders might be predictors of later more serious disorders, such as major depressive disorder (MDD). The purpose of this study is to investigate the association of phobic disorders with the onset of MDD in the community in Japan. Methods: Data from the World Mental Health Japan 2002,2004 Survey were analyzed. A total of 2,436 community residents aged 20 and older were interviewed using the WHO Composite International Diagnostic Interview 3.0 (response rate, 58.4%). A Cox proportional hazard model was used to predict the onset of MDD as a function of prior history of DSM-IV specific phobia, agoraphobia, or social phobia, adjusting for gender, birth-cohort, other anxiety disorders, education, and marital status at survey. Results: Social phobia was strongly associated with the subsequent onset of MDD (hazard ratio [HR]=4.1 [95% CI: 2.0,8.7]) after adjusting for sex, birth cohort, and the number of other anxiety disorders. The association between agoraphobia or specific phobia and MDD was not statistically significant after adjusting for these variables. Conclusions: Social phobia is a powerful predictor of the subsequent first onset of MDD in Japan. Although this finding argues against a simple neurobiological model and in favor of a model in which the cultural meanings of phobia play a part in promoting MDD, an elucidation of causal pathways will require more fine-grained comparative research. Depression and Anxiety, 2009. Published 2009 Wiley-liss, Inc. [source]
Early adversity in chronic depression: clinical correlates and response to pharmacotherapy,,DEPRESSION AND ANXIETY, Issue 8 2009
Daniel N. Klein Ph.D.
Abstract Background: There is growing evidence suggesting that early adversity may be a marker for a distinct pathway to major depressive disorder (MDD). We examined associations between childhood adversity and a broad variety of clinical characteristics and response to pharmacotherapy in a large sample of patients with chronic forms of MDD. Methods: Subjects included 808 patients with chronic forms of MDD (chronic MDD, double depression, or recurrent MDD with incomplete recovery between episodes and a total continuous duration of >2 years) who were enrolled in a 12-week open-label trial of algorithm-guided pharmacotherapy. Baseline assessments included a semi-structured diagnostic interview, and clinician- and self-rated measures of depressive symptoms, social functioning, depressotypic cognitions, and personality traits, and childhood adversity. Patients were re-evaluated every 2 weeks. Results: A longer duration of illness; earlier onset; greater number of episodes, symptom severity, self-rated functional impairment, suicidality, and comorbid anxiety disorder; and higher levels of dysfunctional attitudes and self-criticism were each associated with multiple forms of childhood adversity. A history of maternal overcontrol, paternal abuse, paternal indifference, sexual abuse, and an index of clinically significant abuse each predicted a lower probability of remission. Among patients completing the 12-week trial, 32% with a history of clinically significant abuse, compared to 44% without such a history, achieved remission. Conclusions: These findings indicate that a history of childhood adversity is associated with an especially chronic form of MDD that is less responsive to antidepressant pharmacotherapy. Depression and Anxiety, 2009. Published 2009 Wiley-Liss, Inc. [source]
Antidepressant use in a nationally representative sample of community-dwelling US Latinos with and without depressive and anxiety disorders,DEPRESSION AND ANXIETY, Issue 7 2009
Hector M. González Ph.D.
Abstract Background: Antidepressant drugs are among the most widely prescribed drugs in the United States; however, little is known about their use among major ethnic minority groups. Method: Collaborative Psychiatric Epidemiology Surveys (CPES) data were analyzed to calculate nationally representative estimates of Latino and non-Latino White adults antidepressant use. Setting: The 48 coterminous United States was the setting. Participants: Household residents aged 18 years and older (N=9,250). Main outcome: Past year antidepressant use. Results: Compared to non-Latino Whites, few Latinos, primarily Mexican Americans, with 12-month depressive and/or anxiety disorders reported past year antidepressant use. Mexican Americans (OR=0.48; 95%CI=0.30,0.77) had significantly lower odds of use compared to non-Latino Whites, which were largely unaffected by factors associated with access to care. Over half of antidepressant use was by respondents not meeting 12-month criteria for depressive or anxiety disorders. Lifetime depressive and anxiety disorders explained another 21% of past year antidepressant use, leaving another 31% of drug use unexplained. Discussion: We found a disparity in antidepressant use for Mexican Americans compared to non-Latino Whites that was not accounted for by differences in need and factors associated with access to care. About one third of antidepressant use was by respondents not meeting criteria for depressive or anxiety disorders. Our findings underscore the importance of disaggregating Latino ethnic groups. Additional work is needed to understand the medical and economic value of antidepressant use beyond their primary clinical targets. Depression and Anxiety, 2009. Published 2009 Wiley-Liss, Inc. [source]
Impaired selection of relevant positive information in depressionDEPRESSION AND ANXIETY, Issue 5 2009
Sara M. Levens Ph.D.
Abstract Background: A hallmark characteristic of depression is the inability to regulate the effect of emotional material on cognition. Previous research has demonstrated that depressed individuals are less able than are nondepressed persons to expel irrelevant negative information from working memory (WM), thereby exacerbating the effects of negative content on cognition. The primary goal of this study was to examine whether depressed individuals are also impaired at selecting relevant positive content in the context of representations competing for resources in WM; such an impairment would limit depressed persons' ability to use positive material to ameliorate the cognitive effects of negative information. Methods: We administered a Recency-probes task with neutral, positive, and negative words to 20 currently depressed and 22 never-depressed participants. This task assesses the selection of relevant content in WM by inducing interference between current and prior representations of a stimulus in WM. Reaction times to interference and noninterference trials were compared across valence and group to assess how effectively depressed individuals select task-relevant emotional content to resolve interference. Results: Compared to never-depressed controls, depressed individuals were impaired in selecting task-relevant positive stimuli; the performance of the two groups was comparable for selecting task-relevant neutral and negative stimuli. Conclusions: Findings indicate that a valence-specific deficit in WM may contribute to the inability of depressed individuals to regulate emotion, and provide empirical support for formulations that implicate positive insensitivity in the maintenance of depression. Depression and Anxiety, 2009. Published 2009 Wiley-Liss, Inc. [source]
Atomoxetine treatment in adults with attention-deficit/hyperactivity disorder and comorbid social anxiety disorderDEPRESSION AND ANXIETY, Issue 3 2009
Lenard A. Adler M.D.
Abstract Background: To evaluate the effect of atomoxetine (ATX) on attention-deficit/hyperactivity disorder (ADHD) and comorbid social anxiety disorder in adults. Methods: Randomized, double-blind, placebo-controlled, conducted in adults with ADHD and social anxiety disorder. Patients received 40,100,mg ATX (n=224) or placebo (n=218) for 14 weeks following a 2-week placebo lead-in period. Efficacy measures included the Conners' Adult ADHD Rating Scale: Investigator-Rated: Screening Version (CAARS:Inv:SV), Liebowitz Social Anxiety Scale (LSAS), Clinical Global Impression-Overall-Severity (CGI-O-S), State-Trait Anxiety Inventory (STAI), Social Adjustment Scale-Self Report (SAS), and Adult ADHD Quality of Life Scale-29 (AAQoL). Safety and tolerability were also assessed. Results: ATX mean change (,8.7±10.0) from baseline (29.6±10.4) on CAARS:Inv:SV Total ADHD Symptoms score was significantly greater than placebo mean change (,5.6±10.2) from baseline (31.2±9.4; P<.001). ATX mean change (,22.9±25.3) from baseline (85.3±23.6) on LSAS Total score was significant compared to placebo mean change (,14.4±20.3) from baseline (82.1±21.3; P<.001). The visit-wise analysis revealed greater improvement on the CAARS:Inv:SV Total ADHD Symptoms score and LSAS Total score for ATX at every time point throughout the study (P values ,.012). Mean changes in CGI-O-S, STAI-Trait Anxiety scores, and AAQoL Total score were significantly greater for ATX compared to placebo. Mean change for both groups on STAI-State Anxiety scores was comparable. Improvement on SAS for ATX compared to placebo was not significant. Rates of insomnia, nausea, dry mouth, and dizziness were higher with ATX than with placebo. Discontinuation rates due to treatment-emergent adverse events were similar between groups. Conclusions: ATX monotherapy effectively improved symptoms of ADHD and comorbid social anxiety disorder in adults and was well tolerated. Depression and Anxiety, 2009. Published 2009 Wiley-Liss, Inc. [source]
Gender-specific disruptions in emotion processing in younger adults with depression,DEPRESSION AND ANXIETY, Issue 2 2009
Sara L. Wright Ph.D.
Abstract Background: One of the principal theories regarding the biological basis of major depressive disorder (MDD) implicates a dysregulation of emotion-processing circuitry. Gender differences in how emotions are processed and relative experience with emotion processing might help to explain some of the disparities in the prevalence of MDD between women and men. This study sought to explore how gender and depression status relate to emotion processing. Methods: This study employed a 2 (MDD status) × 2 (gender) factorial design to explore differences in classifications of posed facial emotional expressions (N=151). Results: For errors, there was an interaction between gender and depression status. Women with MDD made more errors than did nondepressed women and men with MDD, particularly for fearful and sad stimuli (Ps <.02), which they were likely to misinterpret as angry (Ps <.04). There was also an interaction of diagnosis and gender for response cost for negative stimuli, with significantly greater interference from negative faces present in women with MDD compared to nondepressed women (P=.01). Men with MDD, conversely, performed similarly to control men (P=.61). Conclusions: These results provide novel and intriguing evidence that depression in younger adults (<35 years) differentially disrupts emotion processing in women as compared to men. This interaction could be driven by neurobiological and social learning mechanisms, or interactions between them, and may underlie differences in the prevalence of depression in women and men. Depression and Anxiety, 2009. Published 2008 Wiley-Liss, Inc. [source]
Obsessive-compulsive disorder among African Americans and blacks of Caribbean descent: results from the national survey of American life,DEPRESSION AND ANXIETY, Issue 12 2008
Joseph A. Himle Ph.D.
Abstract Background: There is limited research regarding the nature and prevalence of obsessive-compulsive disorder (OCD) among various racial and ethnic subpopulations within the United States, including African Americans and blacks of Caribbean descent. Although heterogeneity within the black population in the United States has largely been ignored, notable differences exist between blacks of Caribbean descent and African Americans with respect to ethnicity, national heritage, and living circumstances. This is the first comprehensive examination of OCD among African Americans and blacks of Caribbean descent. Methods: Data from the National Survey of American Life, a national household probability sample of African Americans and Caribbean blacks in the United States, were used to examine rates of OCD among these groups. Results: Lifetime and 12-month OCD prevalence estimates were very similar for African Americans and Caribbean blacks. Persistence of OCD and rates of co-occurring psychiatric disorders were very high and also similar between African American and Caribbean black respondents. Both groups had high levels of overall mental illness severity and functional impairment. Use of services was low for both groups, particularly in specialty mental health settings. Use of anti-obsessional medications was also rare, especially among the Caribbean black OCD population. Conclusions: OCD among African Americans and Caribbean blacks is very persistent, often accompanied by other psychiatric disorders, and is associated with high overall mental illness severity and functional impairment. It is also likely that very few blacks in the United States with OCD are receiving evidence-based treatment and thus considerable effort is needed to bring treatment to these groups. Depression and Anxiety, 2008. Published 2008 Wiley-Liss, Inc. [source]
Cardiac anxiety in people with and without coronary atherosclerosis,DEPRESSION AND ANXIETY, Issue 10 2008
Craig D. Marker Ph.D.
Abstract Many studies have shown that cardiac anxiety when occurring in the absence of coronary artery disease is common and quite costly. The Cardiac Anxiety Questionnaire (CAQ) is an 18-item self-report measure that assesses anxiety related to cardiac symptoms. To better understand the construct of cardiac anxiety, a factor analysis was conducted on CAQ data from 658 individuals who were self or physician-referred for electron beam tomographic screening to determine whether clinically significant coronary atherosclerosis was present. A four-factor solution was judged to provide the best fit with the results reflecting the following factor composition: heart-focused attention, avoidance of activities that bring on symptoms, worry or fear regarding symptoms, and reassurance-seeking. Factorial invariance across groups was also assessed to determine whether the factor structure of the CAQ was similar in individuals with and without clear evidence of coronary atherosclerosis. The factor structure of the CAQ did not differ between the two groups. However, the group without coronary atherosclerosis had significantly higher mean scores on their attention and worry/fear factors suggesting that people without a diagnosed cardiac condition pay more attention to and worry more about their cardiac-related symptoms than those people who have coronary atherosclerosis. Depression and Anxiety 2007. Published 2007 Wiley-Liss, Inc. [source]
Parsing the general and specific components of depression and anxiety with bifactor modeling,DEPRESSION AND ANXIETY, Issue 7 2008
Leonard J. Simms Ph.D.
Abstract Recent hierarchical models suggest that both general and specific components are needed to fully represent the variation observed among mood and anxiety disorders. However, little is known about the relative size, severity, and psychological meaning of these components. We studied these features through bifactor modeling of the symptoms from the Inventory of Depression and Anxiety Symptoms [IDAS; Watson et al., 2007] in 362 community adults, 353 psychiatric patients, and 673 undergraduates. Results revealed that although all IDAS symptom types loaded prominently both on a general factor as well as specific factors, some symptom groups,such as dysphoria, generalized anxiety, and irritability,were influenced more strongly by the general factor, whereas others,e.g., appetite gain, appetite loss, and low well-being,contained a larger specific component. Second, certain symptom groups,e.g., Suicidality, Panic, Appetite Loss, and Ill Temper,reflected higher severity than other symptom groups. Finally, general factor scores correlated strongly with markers of general distress and negative emotionality. These findings support a hierarchical structure among mood and anxiety symptoms and have important implications for how such disorders are described, assessed, and studied. Depression and Anxiety 0:1,13, 2007. Published 2007 Wiley-Liss, Inc. [source]
Anxiety disorders and risk for suicide attempts: findings from the Baltimore Epidemiologic Catchment area follow-up study,DEPRESSION AND ANXIETY, Issue 6 2008
James M. Bolton M.D.
Abstract Our objective was to determine whether the presence of an anxiety disorder was a risk factor for future suicide attempts. Data were drawn from the 13-year follow-up Baltimore Epidemiological Catchment Area survey (n=1,920). Multiple logistic regression analysis was used to determine the association between baseline anxiety disorders (social phobia, simple phobia, obsessive-compulsive disorder, panic attacks, or agoraphobia) and subsequent onset suicide attempts. The presence of one or more anxiety disorders at baseline was significantly associated with subsequent onset suicide attempts (adjusted odds ratio 2.20, 95% confidence interval 1.04,4.64) after controlling for sociodemographic variables and all baseline mental disorders assessed in the survey. These findings suggest that anxiety disorders are independent risk factors for suicide attempts, and underscore the importance of anxiety disorders as a serious public health problem. Depression and Anxiety 0:1,5, 2007. Published 2007 Wiley-Liss. [source]