bluuebunny/crossref_metadata_2025 huggingface dataset:
Convergence of Hormones, Inflammation, and Energy-Related Factors: A Novel Pathway of Cancer Etiology
Authors: Slattery Martha L. , Fitzpatrick F.A.
Published: November 2009

Colorectal cancer (CRC) is a multifactorial disease with several hypothesized etiologic factors including inflammatory processes; hormones such as estrogen, androgen, and insulin; and energy-related factors. We present evidence that integrates these elements in a pathway we call the convergence of hormones, inflammation, and energy-related factors (CHIEF). First, given the physiology of the gut, substantial epidemiologic and molecular data support the hypothesis that activation of innate immunity in the normal gut mucosa by various environmental agents (commensal bacteria, dietary antigens, mucosal irritants, pathogens) and endogenous factors such as estrogen, androgens, and insulin levels provokes basal inflammation as an underlying factor of the association of insulin, estrogen, and energy-related factors with CRC. Second, critical genes involved in this pathway, e.g., phosphatase tensin homologue on chromosome 10 (PTEN) and serine threonine kinase 11 (STK11)/LKB1, are tumor suppressor genes often mutated in intestinal cancer or CRC. Third, laboratory experiments show that cellular PTEN and STK11/LKB1 tumor suppressor enzymes are vulnerable to inactivation by redox-active species, especially chemically reactive lipid mediators of inflammation and redox stress. Epidemiologic data further support the underlying proposal that CHIEF comprises important elements of CRC risk. Although this discussion of the CHIEF pathway focuses on CRC, we believe that this pathway may play an important role in the etiology of other cancers as well.
Autofluorescence-Guided Surveillance for Oral Cancer
Authors: Jayaprakash Vijayvel , Sullivan Maureen , Merzianu Mihai , Rigual Nestor R. , Loree Thom R. , Popat Saurin R. , Moysich Kirsten B. , Ramananda Soumya , Johnson Timothy , Marshall James R. , Hutson Alan D. , Mang Thomas S. , Wilson Brian C. , Gill Steven R. , Frustino Jennifer , Bogaards Arjen , Reid Mary E.
Published: November 2009

Early detection of oral premalignant lesions (OPL) and oral cancers (OC) is critical for improved survival. We evaluated if the addition of autofluorescence visualization (AFV) to conventional white-light examination (WLE) improved the ability to detect OPLs/OCs. Sixty high-risk patients, with suspicious oral lesions or recently diagnosed untreated OPLs/OCs, underwent sequential surveillance with WLE and AFV. Biopsies were obtained from all suspicious areas identified on both examinations (n = 189) and one normal-looking control area per person (n = 60). Sensitivity, specificity, and predictive values were calculated for WLE, AFV, and WLE + AFV. Estimates were calculated separately for lesions classified by histopathologic grades as low-grade lesions, high-grade lesions (HGL), and OCs. Sequential surveillance with WLE + AFV provided a greater sensitivity than WLE in detecting low-grade lesions (75% versus 44%), HGLs (100% versus 71%), and OCs (100% versus 80%). The specificity in detecting OPLs/OCs decreased from 70% with WLE to 38% with WLE + AFV. Thirteen of the 76 additional biopsies (17%) obtained based on AFV findings were HGLs/OCs. Five patients (8%) were diagnosed with a HGL/OC only because of the addition of AFV to WLE. In seven patients, additional HGL/OC foci or wider OC margins were detected on AFV. Additionally, AFV aided in the detection of metachronous HGL/OC in 6 of 26 patients (23%) with a history of previously treated head and neck cancer. Overall, the addition of AFV to WLE improved the ability to detect HGLs/OCs. In spite of the lower specificity, AFV + WLE can be a highly sensitive first-line surveillance tool for detecting OPLs/OCs in high-risk patients.
Origin of Cardiac Fibroblasts and the Role of Periostin
Authors: Snider Paige , Standley Kara N. , Wang Jian , Azhar Mohamad , Doetschman Thomas , Conway Simon J.
Published: November 2009

Abstract:

Cardiac fibroblasts are the most populous nonmyocyte cell type within the mature heart and are required for extracellular matrix synthesis and deposition, generation of the cardiac skeleton, and to electrically insulate the atria from the ventricles. Significantly, cardiac fibroblasts have also been shown to play an important role in cardiomyocyte growth and expansion of the ventricular chambers during heart development. Although there are currently no cardiac fibroblast-restricted molecular markers, it is generally envisaged that the majority of the cardiac fibroblasts are derived from the proepicardium via epithelial-to-mesenchymal transformation. However, still relatively little is known about when and where the cardiac fibroblasts cells are generated, the lineage of each cell, and how cardiac fibroblasts move to reside in their final position throughout all four cardiac chambers. In this review, we summarize the present understanding regarding the function of Periostin, a useful marker of the noncardiomyocyte lineages, and its role during cardiac morphogenesis. Characterization of the cardiac fibroblast lineage and identification of the signals that maintain, expand and regulate their differentiation will be required to improve our understanding of cardiac function in both normal and pathophysiological states.
Significant Compositional Techniques in the Psalms: Evidence for the Use of Number as an Organizing Principle
Authors: Labuschagne Casper
Published: November 2009

This article directs attention to a largely unobserved, and grossly ignored, aspect of the biblical writings in general and of the Psalms in particular: their numerical features. It shall be demonstrated that in composing their texts, the biblical writers used specific numbers as an organizing principle to shape their texts and as a means of imbuing them with symbolic significance. In doing so, they employed a variety of numerical techniques, in which 7 and 11, symbolizing 'fullness' and 'comprehensiveness', play a crucial role as ordering devices. Evidence is adduced to show that the scribes also used the divine name numbers 17 and 26 in various ways to symbolically express God's presence and to give prominence to their texts. Approaching the book of Psalms from this perspective provides us with a new key to unlock and understand the compositional architecture of the psalms and the five books of the Psalter. These claims are substantiated by a discussion of sufficient examples to illustrate that the psalms are interrelated numerical compositions and that the book of Psalms is a sophisticated, meticulously designed work of art, shaped primarily by numerical considerations.
On the Maximum Observed Wind Speed in a Randomly Sampled Hurricane
Authors: Solow Andrew R.
Published: November 2009

There is considerable interest in detecting a long-term trend in hurricane intensity possibly related to large-scale ocean warming. This effort is complicated by the paucity of wind speed measurements for hurricanes occurring in the early part of the observational record. Here, results are presented regarding the maximum observed wind speed in a sparsely randomly sampled hurricane based on a model of the evolution of wind speed over the lifetime of a hurricane.
Great Plains Drought in Simulations of the Twentieth Century
Authors: McCrary Rachel R. , Randall David A.
Published: November 2009

Coupled global circulation models (CGCMs) have been widely used to explore potential future climate change. Before these climate projections can be trusted, the ability of the models to simulate present-day climate must be assessed. This study evaluates the ability of three CGCMs that participated in the Fourth Assessment Report of the Intergovernmental Panel on Climate Change to simulate long-term drought over the Great Plains region with the same frequency and intensity as was observed during the twentieth century. The three models evaluated in this study are the Geophysical Fluid Dynamics Laboratory Coupled Model, version 2.0 (CM2.0); the National Centers for Atmospheric Research Community Climate System Model, version 3 (CCSM3); and third climate configuration of the Met Office Unified Model (HadCM3).

The models are shown to capture the broad features of the climatology of the Great Plains, with maximum precipitation occurring in early summer, as observed. However, all of the models overestimate annual precipitation rates. Also, in CCSM3, precipitation and evapotranspiration experience unrealistic decreases between the months of June and August.

Long-term droughts are found in each simulation of the twentieth century that are comparable in duration, severity, and spatial extent as has been observed. However, the processes found to be associated with simulated long-term droughts vary among the models. In both CM2.0 and HadCM3, low-frequency variations in Great Plains precipitation are found to correspond with low-frequency variations in tropical Pacific SSTs. In CCSM3, on the other hand, there appears to be no significant correlation between tropical Pacific SST variability and Great Plains precipitation. Strong land–atmosphere coupling in CCSM3 may explain the persistence of long-term droughts in this model.
Shallow and Deep Latent Heating Modes over Tropical Oceans Observed with TRMM PR Spectral Latent Heating Data
Authors: Takayabu Yukari N. , Shige Shoichi , Tao Wei-Kuo , Hirota Nagio
Published: November 2009

Three-dimensional distributions of the apparent heat source (Q1) − radiative heating (QR) estimated from Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR) utilizing the spectral latent heating (SLH) algorithm are analyzed. Mass-weighted and vertically integrated Q1 − QR averaged over the tropical oceans is estimated as ∼72.6 J s−1 (∼2.51 mm day−1) and that over tropical land is ∼73.7 J s−1 (∼2.55 mm day−1) for 30°N–30°S. It is shown that nondrizzle precipitation over tropical and subtropical oceans consists of two dominant modes of rainfall systems: deep systems and congestus. A rough estimate of the shallow-heating contribution against the total heating is about 46.7% for the average tropical oceans, which is substantially larger than the 23.7% over tropical land.

Although cumulus congestus heating linearly correlates with SST, deep-mode heating is dynamically bounded by large-scale subsidence. It is notable that a substantial amount of rain, as large as 2.38 mm day−1 on average, is brought from congestus clouds under the large-scale subsiding circulation. It is also notable that, even in the region with SSTs warmer than 28°C, large-scale subsidence effectively suppresses the deep convection, with the remaining heating by congestus clouds.

The results support that the entrainment of mid–lower-tropospheric dry air, which accompanies the large-scale subsidence, is the major factor suppressing the deep convection. Therefore, a representation of the realistic entrainment is very important for proper reproduction of precipitation distribution and the resultant large-scale circulation.
A New Procedure Based on Surface Renewal Analysis to Estimate Sensible Heat Flux: A Case Study over Grapevines
Authors: Castellví F. , Snyder R. L.
Published: November 2009

Grapevines are grown on a range of soils and in different climates. Depending on the desired final product and method of harvesting, the trellis system, and hence vineyard architecture, varies dramatically. Consequently, the crop coefficients used to estimate vineyard evapotranspiration from reference evapotranspiration are less universal than for other crops. Evapotranspiration measurements are often limited because of a lack of fetch and unavailability of vine parameters required as input. In this paper, a new procedure based on surface renewal (SR) analysis was derived to estimate sensible heat flux over the grapevines. A two-dimensional sonic anemometer operating close to the canopy can provide the inputs required to estimate the sensible heat flux and the work of expansion of the air parcels under constant pressure. Regardless of the stability conditions, the SR estimates were comparable to those determined using the eddy covariance (EC) method providing a root-mean-square error of 14 W m−2 for all data. Thus, the procedure is low cost and makes SR a simpler method than EC to estimate latent heat flux as the residual of the energy balance equation in moderately tall and heterogeneous crops. The experiment was carried out at a site influenced by regional advection of sensible heat flux.
The Instability of the Thermohaline Circulation in a Low-Order Model
Authors: Colin de Verdière Alain
Published: November 2009

Although the instability of the thermohaline circulation has been widely observed in numerical ocean models, theoretical advances have been hindered by the nonlinearity of heat and salt transports, a circulation governed by lateral temperature, and salinity gradients. Because the instability occurs initially in polar waters through the formation of haloclines and the halt of convection, any explanatory model must have at least a surface and a deep layer. The model proposed here (two surface boxes above a deep one) reduces to a 2 degrees-of-freedom dynamical system when convection is active and 3 degrees when it is interrupted. The instability that is induced by a negative freshwater perturbation in polar waters has three stages. The first stage is a rapid 5-yr adjustment to a transient thermal attractor that results from an approximate balance between heat advection and air–sea heat fluxes. The second stage is a slow evolution that self-organizes near this attractor, which preconditions the instability, as it can be shown that the circulation becomes more sensitive to changes in salinity gradients than in temperature gradients. The slow O(100 yr) growth of salinity in the subtropics is the critical precursor of the instability while at the same time the subpolar salinity rises against the initial perturbation to stabilize the system by increasing the overturning and restoring convection. When the overturning becomes smaller than the value at the unstable fixed point, the third stage occurs, which is when the subpolar salinity decreases at last on a fast O(10 yr) time scale, precipitating the fall of the overturning. During the last two stages of the instability, the horizontal thermal gradient increases, but its stabilizing effect is just barely unable to prevent the outcome. The return to stability occurs frequently through a regime of multidecadal oscillations with intermittent convection. The hypothesis of mixed boundary conditions has been relaxed by coupling the ocean box model to an atmospheric energy balance model to show that the coupling increases the stability of the oceanic circulation; however, the precursors of the instability are unchanged.
National Identity, Anomie and Mental Health in Latin America
Authors: Parales Quenza Carlos José
Published: November 2009

This article suggests links between the construction of national identities in Latin America, anomie and mental health. Several issues in the process of national identification, including ambivalent independence movements, segregation and the emulation of Spanish social practices, have prevented the inclusion of all segments of the population into collective political projects. Due to exclusion and inequality, there is a persistent condition of anomie, in which social rules become ineffective to regulate the social behaviour of individuals. Dependency and in-group derogation are also counted among the effects of the dysfunctional processes of national identification. Given the influence of social determinants on the health of the population, anomie is considered an important cause of violence and psychosocial problems. The links between anomie and mental health call for a wider perspective to promote mental health and prevent violence and illness. Social participation, equity and citizenship are core themes within this broader perspective.
Newborn Event-Related Potentials Predict Poorer Pre-Reading Skills in Children at Risk for Dyslexia
Authors: Guttorm Tomi K. , Leppänen Paavo H. T. , Hämäläinen Jarmo A. , Eklund Kenneth M. , Lyytinen Heikki J.
Published: November 2009

Earlier results from the Jyväskylä Longitudinal Study of Dyslexia showed that newborn event-related potentials (ERPs) of children with and without familial risk for dyslexia were associated with receptive language and verbal memory skills between 2.5 and 5 years of age. We further examined whether these ERPs (responses to synthetic consonant-vowel syllables /ba/, /da/, /ga/; presented equiprobably with 3,910—7,285 ms interstimulus intervals) predict later pre-reading skills measured before the onset of school (6.5 years of age). In line with our earlier results, the at-risk children ( N = 11) with atypical speech processing in the right hemisphere (a slower shift in polarity from positivity to negativity in responses to /ga/ at 540—630 ms) scored significantly lower in phonological skills, rapid naming, and letter knowledge than the control children ( N = 10) without enhanced right hemispheric speech processing. These results further extend our earlier findings of newborn ERPs in predicting poorer language skills. These consistent differences in ERPs to speech sounds may have applications in the future for the early identification of children at risk for developmental language problems. This would facilitate well-directed intervention even before reading problems are typically diagnosed.
Children With and Without Learning Disabilities: A Comparison of Processes and Outcomes Following Group Counseling
Authors: Leichtentritt Judith , Shechtman Zipora
Published: November 2009

This study compared outcomes and processes in counseling groups of an expressive-supportive modality for children with learning disabilities (LD) and without them (NLD). Participants were 266 students (ages 10—18), all referred for emotional, social, and behavioral difficulties; of these, 123 were identified with LD and 143 were not. There were 40 groups in all—20 with LD children and 20 with NLD. Outcome variables included adjustment, social competence, and academic achievements. Process variables included bonding, group functioning, and client behavior. Analyses were nested using mixed models. Results indicated no differences in outcomes or process variables between populations except for academic achievements; some between-group differences were found in the effect of processes on outcomes. It was concluded that children with LD may be successfully treated in expressive-supportive counseling groups for their emotional and social difficulties.
Percutaneous Gastrojejunostomy Placement in a Heart Failure Patient With Biventricular Assist Devices
Authors: Page Sonya , Cecere Renzo , Valenti David
Published: November 2009

Heart failure patients who require a ventricular assist device often present a nutrition challenge. A 39‐year‐old woman suffering from an acute ST elevated myocardial infarction and severe cardiogenic shock underwent implant of left and right ventricular assist devices (BiVAD). Neurologic deficits prevented her from safely resuming oral intake, and long‐term feeding access was required. The decision was made to insert a percutaneous gastrojejunostomy under fluoroscopic guidance. Patients implanted with ventricular assist devices may require enteral nutrition support. Placement of feeding access other than through the nasoenteric route can be rendered more challenging because of anatomical constraints related to BiVAD positioning; however, whenever enteral nutrition support is required for extended periods, percutaneous or ostomy access offers easier delivery of nutrition. Although technically difficult, successful placement of the enteral feeding tube allowed for continuous 24‐hour feeds to optimize nutrition intake. This is the first time that a percutaneous enteral feeding access was obtained for a ventricular assist device patient at the authors' institution, and it has proven valuable in providing long‐term nutrition in a safe and efficient manner.
Comment on: Measurement of Resting Energy Expenditure in Healthy Children
Authors: Bogucki Elizabeth L.
Published: November 2009

Background: The role that the components of energy expenditure play in the etiology of childhood obesity has highlighted the need for greater accuracy and standardized protocols for the measurement of resting energy expenditure (REE). However, protocols used to assess REE in children are varied, and consensus on a suitable method for measuring REE in children has not been reached. This study was undertaken to determine the effect of measurement time and measurement device (mask or mouthpiece) on REE in healthy children. Design: Following a 12‐hour fast and abstinence from exercise, 23 children (age, 7–12 years) completed two 35‐minute protocols: one with a face mask and the other with a mouthpiece/noseclip. Energy expenditure was measured continuously via indirect calorimetry, while device acceptability was assessed using a 6‐point comfort rating scale. Results: Repeated measures ANOVA indicated that there was no significant difference in REE when measured after 10, 15, 20, or 25 minutes of rest compared to 30 minutes for either the mask or mouthpiece/noseclip (REE range, 1371–1460 kcal/d). Examination of the percentage coefficient of variation (CV) in energy expenditure for each time period by device showed that the least variation existed after 20 minutes of measurement using the mask (CV 6%). Paired t test analysis indicated significantly less discomfort when wearing the mask compared to the mouthpiece/noseclip. Conclusion: It would appear that a 20‐minute protocol using a mask may increase compliance and prove to be a more practical protocol for measuring REE in children.(JPEN J Parenter Enteral Nutr. 2009;33:640‐645)
Malnutrition Syndromes: A Conundrum vs Continuum
Authors: Jensen Gordon L. , Bistrian Bruce , Roubenoff Ronenn , Heimburger Douglas C.
Published: November 2009

This provocative commentary critically examines historic definitions for adult malnutrition syndromes as they apply to developed countries with modern healthcare. To stimulate further discussion, the authors propose an updated approach that incorporates current understanding of the systemic inflammatory response to help guide assessment, diagnosis, and treatment. An appreciation of a continuum of inflammatory response in relation to malnutrition syndromes is described. This discussion serves to highlight a research agenda to address deficiencies in diagnostics, biomarkers, and therapeutics of inflammation in relation to malnutrition.
Colonial Domesticities, Contentious Interactions
Authors: Sen Indrani
Published: November 2009

Nineteenth and early 20th century colonial writings projected the colonial home as a microcosm of the empire. However, as this article argues, the memsahibs’ imperial authority was often undermined by the dynamics of domestic relationships inside the home. Complex and contradictory, they threatened to render the colonial home an ambivalent—and even contested—space. In particular, the location of two female servants inside the colonial nursery—the ayah and the wet-nurse—was problematic. Ayahs were close to European children, who were the next generation of imperial rulers. Often, these children were more attached to their servants than to their parents. An even darker figure was that of the wet-nurse who was universally perceived negatively. This paper draws upon a range of materials from memoirs to medical handbooks to delineate tensions within the imperial home.
Political Awareness and its Implications on Participatory Behaviour
Authors: Amer Moamenla
Published: November 2009

The analysis in this article centres around three questions: First, how well informed are Naga women voters about politics. Second, whether political interest, media exposure and political discussion have an impact on women’s level of political awareness. Third, whether women’s level of political awareness influences their participation in electoral activities. The results indicate that a majority of the women have moderate awareness about politics. Their level of political awareness is accounted for by their level of interest in politics, pattern of media use and frequency of political discussion. The result also reports a limited impact of political awareness on women’s participation in electoral activities.
Women’s Exclusion in Farmer Management of Irrigation Systems in Tamil Nadu
Authors: Dasthagir K. Gulam
Published: November 2009

The Tamil Nadu Farmer Management of Irrigation Systems (TNFMIS) Act (2000) has legalised the participation of registered landowners (men and women) in the management of major and medium irrigation systems in the state. This article analyses the nature and extent of women’s exclusion in the management of a medium irrigation system in this state. The evidence indicates that gender discrimination underlies both land ownership and election strategies to exclude women from participation.
Best Practices for Young Children’s Music Education: Guidance From Brain Research
Authors: Flohr John W.
Published: November 2009

This article reviews best practices for young children’s music experiences in light of developments in brain research. The first section reviews research music and brain topics including neuromyths, effect of music on structural brain changes and general intelligence, plasticity, critical and optimal periods, and at-risk student populations. The second section applies brain research to development and instructional strategies in the elementary music classroom.
Metropoems: Poetic Method and Ethnographic Experience
Authors: Maréchal Garance , Linstead Stephen
Published: November 2009

Discussions of the use and significance of poetry as a research tool have raised the question of poetic technique and craftsmanship in ethnographic poetic outputs. In this article, the authors look explicitly at a contemporary poetic form, the “metropoem” originated by French Oulipian poet Jacques Jouet,1 arguing that it presents a potentially valuable new tool for qualitative research for four reasons. First, the “metropoetic” form enables the taking of a position that neither turns inward toward the ethnographer’s self nor outward toward an empathic relation with the ethnographic other, but is focused in the moment, in place, and in motion—which resists the temptations of nostalgia and Romanticism that have attracted criticism of “research poetry.” Second, it imposes a discipline that is derived from a specific activity, which embodies the rhythms, time, and space of that activity, distinguishing metropoems from poetry that recollects or represents. Third, it demands attention to technique, to poetry as a craft, which underscores calls made by recent critical work in this area. Finally, despite being practically, empirically, and metaphorically enformed by the mobility of contemporary urban social experience, it offers a method that can usefully be adapted to encapsulate other forms of social life.
Shifting horizons
Authors: Smart Carol
Published: November 2009

This article addresses the challenges of developing methodologies which build on the insights of early feminist research and methods, but which also incorporate some of the new innovations in sociological, qualitative research. Feminist research has emphasized the need to capture the everyday lives of women (and others) but this is not so easy once it is realized how ‘messy’ everyday life may be and that we may also not have tools adequate to the art of listening and the task of ‘story telling’. In particular there is a need to incorporate a wide range of sensibilities into the creation of feminist/sociological accounts of everyday lives. These include accounting for emotions, memories, intersubjective meanings, and other intangibles. Finally, the article argues that debates over methodologies should not stop with questions of collecting and analysing data, but must also address the problems of how to write the lives of people differently.
Reducing the Energy Cost of Hemiparetic Gait Using Center of Mass Feedback: A Pilot Study
Authors: Massaad Firas , Lejeune Thierry M. , Detrembleur Christine
Published: November 2009

Background. Hemiparetic gait following stroke requires substantial energy consumption, which would promote deconditioning and disability. Optimal modalities for decreasing this energy cost remain challenging. Excessive energy consumption, however, seems to be mainly due to extra positive muscle work to substantially lift the body’s center of mass (CM) against gravity during the paretic limb swing. Objective. The authors tested a new rehabilitation strategy in a pilot study to specifically reduce the energy cost in hemiparetic gait. Methods. Six chronic hemiparetic patients underwent a 6-week gait training program on a treadmill with real-time feedback of their CM and were asked to reduce its increased vertical displacement. The authors assessed the walking energy cost, vertical CM displacement, kinematics, and electromyogram activity without feedback before and after treatment. Results. After treatment, the vertical CM displacement decreased by 10% ( P = .005), particularly when the CM vaulted over the nonparetic limb in stance, and the energy cost decreased markedly by 30% ( P = .009). The paretic knee flexion in swing increased concomitantly by 45% and muscle co-contraction decreased significantly in both thigh muscles by 15%. Conclusions. The rehabilitation approach followed in this study seems remarkably effective in decreasing the walking energy cost. By treating the compensatory strategy (ie, the increased CM displacement), we also appear to treat primary deviations such as poststroke knee impairments, which is novel and complementary to current concepts in rehabilitation. This new approach is promising and merits further investigation.
Automated summaries of serious adverse events in the hepatitis C antiviral long-term treatment against cirrhosis trial
Authors: Bell Margaret C , Robuck Patricia R , Wright Elizabeth C , Mihova Marina S , Hofmann Charlotte , De Santo Jennifer L , Milstein Susan L , Richtmyer Pamela A , Shelton Janel L , Cormier Maureen , King Debra L , Park Choon J , Molchen Wallis A , Park Yoon , Kelley Michelle
Published: November 2009

Background Even though adverse event (AE) collection and official accounting are mandatory for clinical trials, there are limited detailed guidelines specifying how to summarize the event for reporting in a timely and expeditious manner. This article details the AE and serious adverse event (SAE) reporting summary developed for a large multi-center National Institutes of Health (NIH)-sponsored clinical trial.

Purpose To review and analyze the large volume of AE data reported by 10 sites (806 SAEs and 19,034 AEs from August 2000 to May 2007) the automated SAE summary was developed. It was designed to ensure timeliness and clarity in the complex process of AE review and reporting.

Methods The AE and SAE case report forms (CRFs) as well as the automated SAE summary were developed within a database management system developed by the Data Coordinating Center (DCC) which allowed for web-based data entry at the DCC and 10 sites and offered immediate overall and site-specific reports accessible by the DCC, site, and NIH project staff.

Results The automated SAE summary pulled data from multiple CRFs to create a succinct and informative summary and allowed for prompt and easy reporting to the regulatory agencies. The summary was adaptable to the needs of reviewers because of the availability of multiple search options.
Evidence for a cross-talk between human neutrophils and Th17 cells
Authors: Pelletier Martin , Maggi Laura , Micheletti Alessandra , Lazzeri Elena , Tamassia Nicola , Costantini Claudio , Cosmi Lorenzo , Lunardi Claudio , Annunziato Francesco , Romagnani Sergio , Cassatella Marco A.
Published: November 2009

Interleukin-17A (IL-17A) and IL-17F are 2 of several cytokines produced by T helper 17 cells (Th17), which are able to indirectly induce the recruitment of neutrophils. Recently, human Th17 cells have been phenotypically characterized and shown to express discrete chemokine receptors, including CCR2 and CCR6. Herein, we show that highly purified neutrophils cultured with interferon-γ plus lipopolysaccharide produce the CCL2 and CCL20 chemokines, the known ligands of CCR2 and CCR6, respectively. Accordingly, supernatants from activated neutrophils induced chemotaxis of Th17 cells, which was greatly suppressed by anti-CCL20 and anti-CCL2 antibodies. We also discovered that activated Th17 cells could directly chemoattract neutrophils via the release of biologically active CXCL8. Consistent with this reciprocal recruitment, neutrophils and Th17 cells were found in gut tissue from Crohn disease and synovial fluid from rheumatoid arthritis patients. Finally, we report that, although human Th17 cells can directly interact with freshly isolated or preactivated neutrophils via granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, and interferon-γ release, these latter cells cannot be activated by IL-17A and IL-17F, because of their lack of IL-17RC expression. Collectively, our results reveal a novel chemokine-dependent reciprocal cross-talk between neutrophils and Th17 cells, which may represent a useful target for the treatment of chronic inflammatory diseases.
Information-theoretic gene-gene and gene-environment interaction analysis of quantitative traits
Authors: Chanda Pritam , Sucheston Lara , Liu Song , Zhang Aidong , Ramanathan Murali
Published: November 2009

Background

The purpose of this research was to develop a novel information theoretic method and an efficient algorithm for analyzing the gene-gene (GGI) and gene-environmental interactions (GEI) associated with quantitative traits (QT). The method is built on two information-theoretic metrics, the k-way interaction information (KWII) and phenotype-associated information (PAI). The PAI is a novel information theoretic metric that is obtained from the total information correlation (TCI) information theoretic metric by removing the contributions for inter-variable dependencies (resulting from factors such as linkage disequilibrium and common sources of environmental pollutants).

Results

The KWII and the PAI were critically evaluated and incorporated within an algorithm called CHORUS for analyzing QT. The combinations with the highest values of KWII and PAI identified each known GEI associated with the QT in the simulated data sets. The CHORUS algorithm was tested using the simulated GAW15 data set and two real GGI data sets from QTL mapping studies of high-density lipoprotein levels/atherosclerotic lesion size and ultra-violet light-induced immunosuppression. The KWII and PAI were found to have excellent sensitivity for identifying the key GEI simulated to affect the two quantitative trait variables in the GAW15 data set. In addition, both metrics showed strong concordance with the results of the two different QTL mapping data sets.

Conclusion

The KWII and PAI are promising metrics for analyzing the GEI of QT.
Comparative proteomic analysis of malformed umbilical cords from somatic cell nuclear transfer-derived piglets: implications for early postnatal death
Authors: Park Jong-Yi , Kim Jae-Hwan , Choi Yun-Jung , Hwang Kyu-Chan , Cho Seong-Keun , Park Ho-Hyun , Paik Seung-Sam , Kim Teoan , Park ChanKyu , Lee Hoon Taek , Seo Han Geuk , Park Soo-Bong , Hwang Seongsoo , Kim Jin-Hoi
Published: November 2009

Background

Somatic cell nuclear transfer (scNT)-derived piglets have high rates of mortality, including stillbirth and postnatal death. Here, we examined severe malformed umbilical cords (MUC), as well as other organs, from nine scNT-derived term piglets.

Results

Microscopic analysis revealed complete occlusive thrombi and the absence of columnar epithelial layers in MUC (scNT-MUC) derived from scNT piglets. scNT-MUC had significantly lower expression levels of platelet endothelial cell adhesion molecule-1 (PECAM-1) and angiogenesis-related genes than umbilical cords of normal scNT piglets (scNT-N) that survived into adulthood. Endothelial cells derived from scNT-MUC migrated and formed tubules more slowly than endothelial cells from control umbilical cords or scNT-N. Proteomic analysis of scNT-MUC revealed significant down-regulation of proteins involved in the prevention of oxidative stress and the regulation of glycolysis and cell motility, while molecules involved in apoptosis were significantly up-regulated. Histomorphometric analysis revealed severe calcification in the kidneys and placenta, peliosis in the liver sinusoidal space, abnormal stromal cell proliferation in the lungs, and tubular degeneration in the kidneys in scNT piglets with MUC. Increased levels of apoptosis were also detected in organs derived from all scNT piglets with MUC.

Conclusion

These results suggest that MUC contribute to fetal malformations, preterm birth and low birth weight due to underlying molecular defects that result in hypoplastic umbilical arteries and/or placental insufficiency. The results of the current study demonstrate the effects of MUC on fetal growth and organ development in scNT-derived pigs, and provide important insight into the molecular mechanisms underlying angiogenesis during umbilical cord development.
Identification of differentially expressed miRNAs in chicken lung and trachea with avian influenza virus infection by a deep sequencing approach
Authors: Wang Ying , Brahmakshatriya Vinayak , Zhu Huifeng , Lupiani Blanca , Reddy Sanjay M , Yoon Byung-Jun , Gunaratne Preethi H , Kim Jong Hwan , Chen Rui , Wang Junjun , Zhou Huaijun
Published: November 2009

Background

MicroRNAs (miRNAs) play critical roles in a wide spectrum of biological processes and have been shown to be important effectors in the intricate host-pathogen interaction networks. Avian influenza virus (AIV) not only causes significant economic losses in poultry production, but also is of great concern to human health. The objective of this study was to identify miRNAs associated with AIV infections in chickens.

Results

Total RNAs were isolated from lung and trachea of low pathogenic H5N3 infected and non-infected SPF chickens at 4 days post-infection. A total of 278,398 and 340,726 reads were obtained from lung and trachea, respectively. And 377 miRNAs were detected in lungs and 149 in tracheae from a total of 474 distinct chicken miRNAs available at the miRBase, respectively. Seventy-three and thirty-six miRNAs were differentially expressed between infected and non-infected chickens in lungs and tracheae, respectively. There were more miRNAs highly expressed in non-infected tissues than in infected tissues. Interestingly, some of these differentially expressed miRNAs, including miR-146, have been previously reported to be associated with immune-related signal pathways in mammals.

Conclusion

To our knowledge, this is the first study on miRNA gene expression in AIV infected chickens using a deep sequencing approach. During AIV infection, many host miRNAs were differentially regulated, supporting the hypothesis that certain miRNAs might be essential in the host-pathogen interactions. Elucidation of the mechanism of these miRNAs on the regulation of host-AIV interaction will lead to the development of new control strategies to prevent or treat AIV infections in poultry.
Association of mannose-binding lectin-2 genotype and serum levels with prognosis of sepsis
Authors: Huh Jin Won , Song Kyuyoung , Yum Jung-Sun , Hong Sang-Bum , Lim Chae-Man , Koh Younsuck
Published: November 2009

Introduction

Individuals deficient in mannose-binding lectin (MBL), an important component of the innate immune system, show increased susceptibility to infection. We investigated whether polymorphisms in the MBL2 gene and the serum level are associated with the severity and prognosis of sepsis.

Methods

A total of 266 patients with sepsis and 398 healthy controls were enrolled. We analyzed the three single nucleotide polymorphisms (Gly54Asp, -550, and +4) in the MBL2 gene. Serum samples collected on day 1 were analyzed for the levels of MBL.

Results

Patients who were heterozygous (A/B) or homozygous (B/B) at codon 54 (adjusted odds ratio (OR), 0.370; 95% confidence interval (CI), 0.207-0.661, P = 0.001) and who were heterozygous (H/L) or homozygous (L/L) at -550 (adjusted OR, 0.476; 95% CI, 0.249-0.910, P = 0.025) were less likely to have septic shock in the sepsis group. Using Cox regression analysis for 28-day mortality, an MBL level ≥ 1.3 microg/mL showed significantly lower 28-day mortality (P = 0.020; hazard ratio, 0.571; 95% CI, 0.355-0.916) in the septic shock group.

Conclusions

Homozygosity at codons 54 (A/A) and -550 (H/H) appears to be associated with the severity, but not the outcome, of sepsis, whereas a low MBL level may be an independent risk factor for mortality. These findings suggest that the genotype and serum level for MBL2 may have different clinical implications.
Management of self-harm in older people
Authors: Toms Nikki D. , Ritchie Craig W.
Published: November 2009

Aims and Method

The epidemiology of self-harm in older people is poorly understood and a low incidence rate hampers research efforts. Regional surveillance for this may assist with research and improve clinical services accordingly. This study involved undertaking a scoping exercise to explore current management of self-harm in elderly people in selected North London hospitals, by interviewing healthcare professionals directly involved in their treatment.

Results

The study showed varied methods of coding clinical information across trusts, with no consistent method of surveillance.

Clinical Implications

Implications of this exercise involve generation of a summary document that will educate stage two of the project, which is the convention of a working party to implement a surveillance system across the region.
Leadership development: more than on-the-job training
Authors: Buckley Peter F.
Published: November 2009

The effective psychiatric leader in clinical administration must possess organisational knowledge, financial acumen, negotiation and conflict resolution skills, and a broad knowledge of our field. Team building, motivating others, mentorship, and the ability to hire excellent colleagues are all important attributes of leadership. It is opportune for our profession to promote training and skill acquisition in leadership development.
Synergy of Total PLAC4 RNA Concentration and Measurement of the RNA Single-Nucleotide Polymorphism Allelic Ratio for the Noninvasive Prenatal Detection of Trisomy 21
Authors: Tsui Nancy BY , Akolekar Ranjit , Chiu Rossa WK , Chow Katherine CK , Leung Tak Y , Lau Tze K , Nicolaides Kypros H , Lo YM Dennis
Published: November 2009

Background: Maternal plasma mRNA encoded by the PLAC4 gene (placenta-specific 4), which is transcribed from chromosome 21 in placental cells, is a potential marker for the noninvasive assessment of chromosome 21 dosage in the fetus. We evaluated the diagnostic sensitivities and specificities of 2 trisomy 21–screening approaches that use maternal plasma PLAC4 mRNA.

Methods: We studied maternal plasma samples from 153 pregnant women carrying euploid and trisomy 21 fetuses. For the samples in which the fetuses were heterozygous for the studied PLAC4 single-nucleotide polymorphism (SNP), we measured the ratio between 2 alleles of the SNP in maternal plasma PLAC4 mRNA (RNA-SNP) by mass spectrometric (MS) and digital PCR methods. For pregnancies involving fetuses homozygous for the SNP, we quantified the total PLAC4 mRNA concentration in maternal plasma by real-time PCR and digital PCR.

Results: For the RNA-SNP approach, we achieved a diagnostic sensitivity and specificity of 100% (95% CI, 40.2%–100%) and 89.7% (95% CI, 78.8%–96.1%), respectively, for both the MS and the digital PCR methods. For the mRNA-quantification approach, the areas under the ROC curves were 0.859 (95% CI, 0.741–0.903) and 0.833 (95% CI, 0.770–0.923) for plasma PLAC4 mRNA concentrations measured by the real-time PCR and the digital PCR methods, respectively.

Conclusions: For prenatal screening of trisomy 21, the quantification of the total PLAC4 mRNA concentration can be used in a synergistic manner with the RNA-SNP allelic ratio approach to increase the population coverage of cases in which diagnostic information can be obtained.
Determination of Plastic and Liquid Limits Using the Reverse Extrusion Technique
Authors: Kayabali Kamil , Tufenkci Osman Oguz
Published: November 2009

Consistency limits are fundamental properties of fine grained soils. The techniques used today to determine these parameters are operator dependent; their repeatability is low. In order to overcome and/or reduce those factors affecting the results of conventional testing methods, the reverse extrusion technique was evaluated. Thirty-one inorganic soil samples were used in the experiments. In order to produce a reliable basis for the plastic and liquid limits, a relatively broad database was constituted using the conventional consistency limit tests. Extrusion pressures were then obtained and plotted for different water contents for each sample. A linear relationship was observed among the water content and the logarithm of the extrusion pressure. The extrusion pressures corresponding to the average plastic and liquid limits of the conventional method show a normal distribution about certain values. A more reliable, economical, and robust device with greater repeatability is proposed. The presented approach shows promise in providing a better index parameter to characterize fine grained soils.
Neuromyelitis optica spectrum: novel concept of pathogenesis, diagnosis and treatment of Devic’s disease
Authors: Csécsei Péter , Trauninger Anita , Komoly Sámuel , Illés Zsolt
Published: November 2009

The identification of autoantibodies generated against the brain isoform water channel aquaporin4 in the sera of patients, changed the current diagnostic guidelines and concept of neuromyelitis optica (NMO). In a number of cases, clinical manifestation is spatially limited to myelitis or relapsing optic neuritis creating a diverse. NMO spectrum. Since prevention of relapses provides the only possibility to reduce permanent disability, early diagnosis and treatment is mandatory. In the present study, we discuss the potential role of neuroimaging and laboratory tests in differentiating the NMO spectrum from other diseases, as well as the diagnostic procedures and therapeutic options. We also present clinical cases, to provide examples of different clinical settings, diagnostic procedures and therapeutic decisions.
Monoicy in A. angustifolia (Bert.) O. Kuntze (Araucariaceae): I. Morphological aspects of the reproductive structures
Authors: Stefenon Valdir M. , Caprestano Clarissa A.
Published: November 2009

Araucaria angustifolia (Bert.) O. Kuntze is a dioecious conifer species native of Brazil. The rare occurrence of monoiceous specimens have been attributed to pathogenic infections or other injuries in adult trees. Here, the morphological characteristics of male and female cones and pollen grains of a monoiceous A. angustifolia are described. Male and female cones and pollen grains presented normal morphology, lacking any sort of injuries or infection and suggesting the existence of further grounds for the occurrence of monoicy in this conifer species.