bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum γ-Glutamyl Transferase and Risk of Heart Failure in the Community
Authors: Dhingra Ravi , Gona Philimon , Wang Thomas J. , Fox Caroline S. , D'Agostino Ralph B. , Vasan Ramachandran S.
Published: June 2010

Objective—

To examine the association of serum γ-glutamyltransferase (GGT) with incident heart failure.

Methods and Results—

We related serum GGT to the incidence of heart failure in 3544 (mean age, 44.5 years; 1833 women and 1711 men) Framingham Study participants who were free of heart failure and myocardial infarction. On follow-up (mean, 23.6 years), 188 participants (77 women) developed new-onset heart failure. In multivariable Cox proportional hazards regression models adjusting for standard risk factors and alcohol consumption as time-varying covariates (updated every 4 years), each SD increase in log-GGT was associated with a 1.39-fold risk of heart failure (95% CI, 1.20 to 1.62). The linearity of the association was confirmed by multivariable-adjusted splines, and the relations remained robust on additional adjustment for hepatic aminotransferases and C-reactive protein. Participants with a serum GGT level at the median or greater had a 1.71-fold risk of heart failure (95% CI, 1.21 to 2.41) compared with individuals with GGT concentrations less than the median. GGT marginally increased the model C-statistic from 0.85 to 0.86 but improved the risk reclassification modestly (net reclassification index, 5.7%;
P
=0.01).

Conclusion—

In this prospective study of a large community-based sample, higher serum GGT concentrations within the “normal” range were associated with greater risk of heart failure and incrementally improved prediction of heart failure risk.
Alterations of L-Type Calcium Current and Cardiac Function in CaMKIIδ Knockout Mice
Authors: Xu Lin , Lai Dongwu , Cheng Jun , Lim Hyun Joung , Keskanokwong Thitima , Backs Johannes , Olson Eric N. , Wang Yanggan
Published: June 2010

Rationale:

Recent studies have highlighted important roles of CaMKII in regulating Ca2+handling and excitation-contraction coupling. However, the cardiac effect of chronic CaMKII inhibition has not been well understood.

Objective:

We have tested the alterations of L-type calcium current (ICa) and cardiac function in CaMKIIδ knockout (KO) mouse left ventricle (LV).

Methods and Results:

We used the patch-clamp method to record ICain ventricular myocytes and found that in KO LV, basal ICawas significantly increased without changing the transmural gradient of ICadistribution. Substitution of Ba2+for Ca2+showed similar increase in IBa. There was no change in the voltage dependence of ICaactivation and inactivation. ICarecovery from inactivation, however, was significantly slowed. In KO LV, the Ca2+-dependent ICafacilitation (CDF) and ICaresponse to isoproterenol (ISO) were significantly reduced. However, ISO response was reversed by β2-adrenergic receptor (AR) inhibition. Western blots showed a decrease in β1-AR and an increase in Cav1.2, β2-AR, and Gαi3 protein levels. Ca2+transient and sarcomere shortening in KO myocytes were unchanged at 1-Hz but reduced at 3-Hz stimulation. Echocardiography in conscious mice revealed an increased basal contractility in KO mice. However, cardiac reserve to work load and β-adrenergic stimulation was reduced. Surprisingly, KO mice showed a reduced heart rate in response to work load or β-adrenergic stimulation.

Conclusions:

Our results implicate physiological CaMKII activity in maintaining normal ICa, Ca2+handling, excitation-contraction coupling, and the in vivo heart function in response to cardiac stress.
Formation of Plexiform Lesions in Experimental Severe Pulmonary Arterial Hypertension
Authors: Abe Kohtaro , Toba Michie , Alzoubi Abdallah , Ito Masako , Fagan Karen A. , Cool Carlyne D. , Voelkel Norbert F. , McMurtry Ivan F. , Oka Masahiko
Published: June 2010

Background—

The plexiform lesion is the hallmark of severe pulmonary arterial hypertension. However, its genesis and hemodynamic effects are largely unknown because of the limited availability of lung tissue samples from patients with pulmonary arterial hypertension and the lack of appropriate animal models. This study investigated whether rats with severe progressive pulmonary hypertension developed plexiform lesions.

Methods and Results—

After a single subcutaneous injection of the vascular endothelial growth factor receptor blocker Sugen 5416, rats were exposed to hypoxia for 3 weeks. They were then returned to normoxia for an additional 10 to 11 weeks. Hemodynamic and histological examinations were performed at 13 to 14 weeks after the Sugen 5416 injection. All rats developed pulmonary hypertension (right ventricular systolic pressure ≈100 mm Hg) and severe pulmonary arteriopathy, including concentric neointimal and complex plexiform-like lesions. There were 2 patterns of complex lesion formation: a lesion forming within the vessel lumen (stalk-like) and another that projected outside the vessel (aneurysm-like). Immunohistochemical analyses showed that these structures had cellular and molecular features closely resembling human plexiform lesions.

Conclusions—

Severe, sustained pulmonary hypertension in a very late stage of the Sugen 5416/hypoxia/normoxia-exposed rat is accompanied by the formation of lesions that are indistinguishable from the pulmonary arteriopathy of human pulmonary arterial hypertension. This unique model provides a new and rigorous approach for investigating the genesis, hemodynamic effects, and reversibility of plexiform and other occlusive lesions in pulmonary arterial hypertension.
Paramedic Diagnosis of Stroke
Authors: Bray Janet E. , Coughlan Kelly , Barger Bill , Bladin Chris
Published: June 2010

Background and Purpose—

Recent evidence suggests the Cincinnati Prehospital Stroke Scale is ineffectively used and lacks sensitivity and specificity. Melbourne (Australia) paramedics have been using the Melbourne Ambulance Stroke Screen (MASS) since 2005. The aim of this study was to review the real-world use of MASS 3 years after citywide implementation.

Methods—

Two groups of consecutively admitted patients to an Australian hospital between January and May 2008 were used: (1) patients for whom paramedics performed MASS; and (2) patients with a discharge diagnosis of stroke or transient ischemic attack. Use of MASS was examined for all transports and for patients diagnosed with stroke or transient ischemic attack. The sensitivity and specificity of paramedic diagnosis, MASS, and Cincinnati Prehospital Stroke Scale were calculated. Paramedic diagnosis of stroke among patients with stroke was statistically compared with those obtained immediately post-MASS implementation in 2002.

Results—

For the study period, MASS was performed for 850 (16%) of 5286 emergency transports, including 199 of 207 (96%) patients with confirmed stroke and transient ischemic attack. In patients in whom MASS was performed (n=850), the sensitivity of paramedic diagnosis of stroke (93%, 95% CI: 88% to 96%) was higher than the MASS (83%, 95% CI: 77% to 88%,
P
=0.003) and equivalent to Cincinnati Prehospital Stroke Scale (88%, 95% CI: 83% to 92%,
P
=0.120), whereas the specificity of the paramedic diagnosis of stroke (87%, 95% CI: 84% to 89%) was equivalent to MASS (86%, 95% CI: 83% to 88%,
P
=0.687) and higher than Cincinnati Prehospital Stroke Scale (79%, 95% CI: 75% to 82%,
P
<0.001). The initial improvement in stroke paramedic diagnosis seen in 2002 (94%, 95% CI: 86% to 98%) was sustained in 2008 (89%, 95% CI: 84% to 94%,
P
=0.19).

Conclusion—

In our experience, paramedics have successfully incorporated MASS into the assessment of neurologically compromised patients. The initial improvement to the paramedics’ diagnosis of stroke with MASS was sustained 3 years after citywide implementation.
Improvement in Aphasia Scores After Stroke Is Well Predicted by Initial Severity
Authors: Lazar Ronald M. , Minzer Brandon , Antoniello Daniel , Festa Joanne R. , Krakauer John W. , Marshall Randolph S.
Published: June 2010

Background and Purpose—

Most improvement from poststroke aphasia occurs within the first 3 months, but there remains unexplained variability in recovery. Recently, we reported a strong correlation between initial impairment and change scores in motor recovery at 90 days. We wanted to determine whether aphasia recovery (defined as a change from baseline to 90 days) shows a comparably strong correlation and whether the relation was similar to that in motor recovery.

Methods—

Twenty-one stroke patients had aphasia scores on the Western Aphasia Battery (WAB) obtained on stroke admission (WAB
initial
) and at 90 days (WAB
3 mo
). The relation between actual change (Δ) scores (defined as WAB
3 mo
− WAB
initial
) and WAB
initial
was calculated in multiple-regression analysis.

Results—

Regression analysis demonstrated that WAB
initial
was highly correlated with ΔWAB (
R
2
=0.81,
P
<0.001) and that, in addition, the relation between WAB
initial
and ΔWAB was proportional, such that patients recovered 0.73 of maximal potential recovery (WAB
maximum
−WAB
initial
).

Conclusions—

We show that, like motor recovery, there is a highly predictable relation between aphasia recovery and initial impairment, which is also proportional in nature. The comparability of recovery from motor and language impairment suggests that common mechanisms may govern reduction of poststroke neurologic impairment across different functional domains and that they could be the focus of therapeutic intervention.
Plasma Magnesium Concentrations and Clinical Outcomes in Aneurysmal Subarachnoid Hemorrhage Patients
Authors: Wong George K.C. , Poon Wai S. , Chan Matthew T.V. , Boet Ronald , Gin Tony , Ng Stephanie C.P. , Zee Benny C.Y.
Published: June 2010

Background and Purpose—

Conflicting data have been obtained on optimal plasma magnesium concentrations for clinical outcomes in patients with aneurysmal subarachnoid hemorrhage.

Methods—

Adults (aged 18 years or older) who had acute aneurysmal subarachnoid hemorrhage diagnosed were randomly assigned to receive either an intravenous MgSO
4
infusion (80 mmol in 500 mL normal saline per day) or a placebo (500 mL normal saline per day) for up to 14 days. Post hoc multivariable binary logistic regression analyses were performed by dividing mean plasma magnesium concentrations into 4 quartiles according to treatment group and then comparing with the lowest quartiles.

Results—

The worst clinical outcomes at 6 months were seen in MgSO
4
group patients, with mean plasma magnesium concentrations in the fourth quartile, and in placebo group patients, with mean such concentrations in the third and fourth quartiles.

Conclusions—

No evidence was found to suggest that a higher mean plasma magnesium concentration improves clinical outcomes. On the contrary, we found an association between high plasma magnesium concentration and worse clinical outcomes.
Comparison of Satellite Cloud Masks with Ceilometer Sky Conditions in Southern Finland
Authors: Joro Sauli , Hyvärinen Otto , Kotro Janne
Published: June 2010

The cloud mask is an essential product derived from satellite data. Whereas cloud analysis applications typically make use of information from cloudy pixels, many other applications require cloud-free conditions. For this reason many organizations have their own cloud masks tuned to serve their particular needs. Being a fundamental product, continuous quality monitoring and validation of these cloud masks are vital. This study evaluated the performance of the European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT) Meteorological Products Extraction Facility cloud mask (MPEF), together with the Nowcasting Satellite Application Facility (SAFNWC) cloud masks provided by Météo-France (SAFNWC/MSG) and the Swedish Meteorological and Hydrological Institute (SAFNWC/PPS), in the high-latitude area of greater Helsinki in Finland. The first two used the Spinning Enhanced Visible and Infrared Imager (SEVIRI) instrument from the geostationary Meteosat-8 satellite, whereas the last used the Advanced Very High Resolution Radiometer (AVHRR) instrument on board the polar-orbiting NOAA satellite series. Ceilometer data from the Helsinki Testbed, an extensive observation network covering the greater Helsinki area in Finland, were used as reference data in the cloud mask comparison. A computational method, called bootstrapping, is introduced to account for the strong temporal and spatial correlation of the ceilometer observations. The method also allows the calculation of the confidence intervals (CI) for the results. This study comprised data from February and August 2006. In general, the SAFNWC/MSG algorithm performed better than MPEF. Differences were found especially in the early morning low cloud detection. The SAFNWC/PPS cloud mask performed very well in August, better than geostationary-based masks, but had problems in February when its performance was worse. The use of the CIs gave the results more depth, and their use should be encouraged.
Mechanisms Affecting the Transition from Shallow to Deep Convection over Land: Inferences from Observations of the Diurnal Cycle Collected at the ARM Southern Great Plains Site
Authors: Zhang Yunyan , Klein Stephen A.
Published: June 2010

Summertime observations for 11 yr from the Atmospheric Radiation Measurement (ARM) Climate Research Facility Southern Great Plains (SGP) site are used to investigate mechanisms controlling the transition from shallow to deep convection over land. It is found that a more humid environment immediately above the boundary layer is present before the start of late afternoon heavy precipitation events. The higher moisture content is brought by wind from the south. Greater boundary layer inhomogeneity in moist static energy, temperature, moisture, and horizontal wind before precipitation begins is correlated to larger rain rates at the initial stage of precipitation. In an examination of afternoon rain statistics, higher relative humidity above the boundary layer is correlated to an earlier onset and longer duration of afternoon precipitation events, whereas greater boundary layer inhomogeneity and atmospheric instability in the 2–4-km layer above the surface are positively correlated to the total rain amount and the maximum rain rate. Although other interpretations may be possible, these observations are consistent with theories for the transition from shallow to deep convection that emphasize the role of a moist lower free troposphere and boundary layer inhomogeneity.
Mesoscale Cyclone Activity over the Ice-Free Southern Ocean: 1999–2008
Authors: Irving Damien , Simmonds Ian , Keay Kevin
Published: June 2010

Mesoscale cyclones play an important role in the weather and climate of the Southern Hemisphere (SH) mid-to-high latitudes. However, the relatively small size and short lifetime of these systems, combined with the lack of available conventional data in this region, means that there is a poor understanding of their climatological characteristics. In this study, the University of Melbourne cyclone-finding algorithm was applied to relatively high-resolution scatterometer-derived surface pressure fields, obtained from the Department of Atmospheric Sciences at the University of Washington, to produce a decade-long (1999–2008) seasonal climatology of mesoscale cyclone activity over the ice-free regions of the Southern Ocean.

The frequency of mesoscale cyclone activity was found to be highest just to the north of the sea ice zone, reaching a maximum over the Amundsen and Bellingshausen Seas (ABS), while the southern Indian Ocean was associated with systems of the largest depth, intensity, and momentum flux at the ocean surface. These spatial patterns in mean mesoscale cyclone characteristics showed a broad resemblance to those reported in existing synoptic-scale cyclone climatologies. Maximum wind speed data indicated that SH polar lows may be more frequent than the current literature suggests, while strong positive trends identified in mesoscale cyclone frequency over the ABS may represent a contributing factor to the rapid warming observed in that region over recent years. Partial correlation analyses indicated a link between mesoscale cyclone frequency and the southern annular mode.
‘I Hate Your Church; What I Want is My Kingdom’: Emerging Spiritualities in the UK Emerging Church Milieu
Authors: Moody Katharine Sarah
Published: June 2010

This article assesses current approaches to defining the emerging church. It argues for the value of the concept of a milieu, introducing the emerging church as a diverse transnational milieu of individuals, networks, organisations and collectives who are variously involved in exploring Christianity in the post- or late-modern missional contexts of the West today. It identifies two spiritualities that emerge from this milieu, and asks whether they are church- or kingdom-focused.
The Teacher-Pupil Observation Tool (T-POT)
Authors: Martin P.A. , Daley D. , Hutchings J. , Jones K. , Eames C. , Whitaker C.J.
Published: June 2010

Teacher-pupil relationships do not solely impact children’s academic development; they also influence emotional and behavioural development. Positive teacher-pupil relationships help reduce maladaptive behaviour while negative ones can lead to increased academic, social and behavioural difficulties. Identifying and measuring teacher-pupil relationship through classroom behaviours and interactions is therefore important as an index of classroom-based influences on child outcome. This article illustrates the development and testing of a classroom observation measure - the Teacher-Pupil Observation Tool (T-POT) - in a small-scale study of 12 teachers and 107 children in 12 reception classrooms. To assess validity and reliability, observed behaviours on the T-POT were correlated with each other (internal validity), and with teacher rated reports of classroom behaviour (discriminant and concurrent validity). Observer agreement was also assessed (inter-rater reliability). The T-POT showed promising psychometric properties in all cases. The T-POT is currently the main outcome measure in four funded evaluation studies in Gwynedd, North Wales, and an outcome measure in a funded evaluation study in Clondalkin, Ireland. These studies will further benefit the measure’s validity and reliability and test the sensitivity of the T-POT in detecting change in teacher-pupil behaviour over time.
School and Home Relationships and Their Impact on School Bullying
Authors: Murray-Harvey Rosalind , Slee Phillip T.
Published: June 2010

Previous school-related bullying research focused largely on inter-relationships among perpetrators and victims and more recently has included influences on, and by, peers. Still, less attention is given to wider school relationships that consider families and teachers. Students across grades 5—9 in 22 South Australian schools reported on how well they felt supported by their peers, families and teachers and the extent to which they perceived these groups as sources of stress in their lives at school. Six hundred and twenty-one teachers also assessed their students’ adaptive and non-adaptive behaviour. Links between stress and support and students’ experience of school, including bullying and victimization were examined using path analysis. Along with the expected impact of poor peer relationships and bullying/victimization, relationships with teachers exerted an equally powerful influence on students’ reports of bullying. Teachers need to be made aware that developing strong supportive relationships with students has a flow-on effect of reducing bullying.
Teacher-Student Relationship: The Influence of Teacher Interpersonal Behaviours and Perceived Beliefs about Teachers on the School Adjustment of Low Achieving Students in Asian Middle Schools
Authors: Wan Har Chong  , Huan Vivien S. , Choon Lang Quek  , Lay See Yeo  , Ang Rebecca P.
Published: June 2010

This study investigated aspects of the teacher-student relationship as they relate to school adjustment with 523 Grade 8 students in Singapore. The first question examined what configurations of teacher-student support could be identified with low-achieving students. Cluster analysis identified two sub-groups on the basis of specific qualities of the teacher-student relationship and patterns of teacher interpersonal behaviours in the classroom deemed important for improving the psychosocial aspects of their school experience. The second question examined the contribution of these teacher-student relationship variables in predicting school adjustment for each cluster. Finally, post hoc analyses showed students’ attitude toward teachers was significant in mediating between teacher-student relational quality and school liking. Implications from the study were discussed.
Educating for Democracy
Authors: Cam Philip
Published: June 2010

The author, a specialist in philosophy for children who is recognized worldwide, presents the conceptual and philosophical framework within which the idea of early education in philosophical discussion is situated. A theory of education and its place in social and cultural development is the precondition to any practice aimed at doing philosophy with children.
Retracing the Path of the Sons of Hilal
Authors: Galley Micheline
Published: June 2010

The article aims to contribute to a wider knowledge of the Hilâl epic, a masterwork of popular Arabic literature that tells the story of a nomadic pastoral people from the Arabian deserts. The focus is on the ‘Taghrîba’ cycle, which relates the migration in the 11th century of these Sons of Hilâl to Ifrîqiyya, present-day Tunisia.

In this context reference is made to the political act of the Fatimid power that launched the Hilalians on the conquest of Ifrîqiyya, as well as to historians’ and linguists’ perception of it. But interest is centred more on the texts, which are copiously quoted, their poetic quality and their message – the expression of a tribal humanism, composed of grandeur and human dignity, particular to those desert people.
Flame Retardancy of Wool Fabric with Zirconium Oxychloride Optimized by Central Composite Design
Authors: Forouharshad M. , Montazer M. , Bameni Moghadam M. , Saligheh O.
Published: June 2010

In this study, the effect of zirconium oxychloride (ZrOCl2) with different concentrations of citric and formic acids on the flame-retardant properties of wool is assessed by thermal analysis, mass loss, the limiting oxygen index (LOI) and the vertical flame. Scanning electron micrographs have been prepared to observe and compare the surface morphology of the raw and treated samples. It has been observed that the ZrOCl2 exhausted onto wool and the flame retardancy natural markedly improved. The wool treated with the flame-retardant agents show an increase in the temperature of decomposition and residual mass and LOI compared with the untreated wool. The central composite design (CCD) is used for the experimental design with four variables. The statistical analysis confirmed the optimum conditions obtained by the experimental results, in which the processing optimized at 94.9°C with 9.74% zirconium oxychloride, 9.6% citric acid, and 6.3% formic acid.
“The Only 13-Year-Old on Planet Earth Without a Cell Phone”: Meanings of Cell Phones in Early Adolescents’ Everyday Lives
Authors: Blair Bethany L. , Fletcher Anne C.
Published: June 2010

Cellular telephones have become an increasingly prevalent feature of contemporary American life, with usage often beginning during early adolescence. With this in mind, twenty 7th graders and their mothers participated in separate qualitative interviews regarding early adolescents’ use of cell phones as well as perceived risks and benefits of such use. Analyses indicated that early adolescents and their mothers imbued cell phones with a variety of psychological meanings. These meanings included cell phones as a source of connection to family and friends, cell phones as facilitators of adolescent autonomy development, and cell phones as sources of social status.These findings are discussed in relation to psychosocial developmental tasks occurring in early adolescence.
Subcontracting in India’s Unorganised Manufacturing Sector
Authors: Sahu Partha Pratim
Published: June 2010

The article provides empirical evidence on the pattern and magnitude of subcontracting in micro and small manufacturing enterprises sector and across its different industry groups and analyses whether there are any sector-specific features in functions and linkages. It illustrates types, nature and extent of linkages and their implications for the micro and small enterprises. In terms of select performance indicators, a comparative analysis of enterprises that are engaged in subcontracts and those that are not has been attempted to identify factors that work for or against long term relationships between the large and micro and small firms. Subcontracting as an instrument for technological upgradation and employment expansion in micro and small manufacturing enterprises has also been discussed. The article shows that the subcontracting intensities were pronounced in very few product lines. Although the subcontracting enterprises were reported of receiving assistances in terms of marketing, technology and finance, these enterprises were operating at a lower productivity level as compared to non-subcontracting enterprises. Further comparison of employment generation capacity between subcontracting and non-subcontracting enterprises does not reveal any pattern. The article concludes with a summary of the article and suggests policies that can potentially impinge on subcontracting linkages for optimal outcomes.
Risk, Need, and Responsivity: Unrealized Potential for the International Delivery of Substance Abuse Treatment in Prison
Authors: Jolley Jennifer M. , Kerbs John J.
Published: June 2010

Drawing from a strong Canadian and U.S. base of literature and an emergent base of scholarship from the United Kingdom, this article examines the delivery of substance abuse treatment in prisons and the determinants of prisoner access to and use of services. To date, multidisciplinary research provides evidence of supply-side programs driven by organizational factors that affect access and use; in contrast, there is a dearth of literature on demand-side programs driven by prisoners’ needs. Guiding this analysis is a model for service delivery that integrates supply- and demand-side factors into a framework that traces the pathway of prisoners through programs, beginning with assessment and ending with treatment outcomes. At the core of this analysis is an expanded discussion of how prisoners’ specific needs should inform service delivery for greater reductions in rates of relapse and recidivism. Conclusions examine the legal and socioeconomic policy implications of programs that fail to provide services according to offenders’ specific needs in Canada, the United Kingdom, and the United States.
Pulmonary Embolism and Pulmonary Infarction After Lung Transplantation
Authors: Krivokuca Igor , van de Graaf Ed A. , van Kessel Diana A. , van den Bosch Jules M. M. , Grutters Jan C. , Kwakkel-van Erp Johanna M.
Published: June 2010

Venous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep vein thrombosis (DVT), is a common occurrence in patients undergoing surgery and is a potentially fatal complication. Especially after lung transplantation, vascular complications can compromise the function of the allograft and limit survival. Typically, the risk of pulmonary infarction after PE in lung transplant recipients is high because the absence or poor development of the collateral bronchial circulation may predispose lung transplant recipients to pulmonary infarction. This article reports 2 cases of PE with associated pulmonary infarction after lung transplantation with significant morbidity.
The Gender of Geographical Indications: Women, Place, and the Marketing of Identities
Authors: Parasecoli Fabio
Published: June 2010

In Western Europe and in the United States, a rekindled interest in food and wine has stimulated the development of value-based food labels that define products based on their immaterial, cultural, and also political contents; among these, the geographical indications (GIs), now protected by the World Trade Organization, refer principally to the place of origin of the product. Despite their commercial and cultural relevance, the evaluation of the impact of GIs on a community usually does not consider gender issues, often misrepresenting or ignoring women’s role as the keepers of local traditions, especially in the case of seeds, shepherding products, and their culinary uses. This article (a) analyzes the relationships between gender, place, and local tradition in the case of GIs (b) and addresses the questions of who reaps the benefits of techniques and know-how transmitted and protected by women, and how the role of women is acknowledged in the developing regulations regarding the products involved.
Endovascular Repair of Abdominal Aortic Aneurysm With Extreme Iliac Artery Tortuosity
Authors: Rahimi Saum A. , O'Donnell Paul L. , Graham Alan M.
Published: June 2010

Iliac artery tortuosity can be a limiting factor in treating abdominal aortic aneurysms by endovascular means. In this case, a 6F catheter guiding sheath was used to allow tracking of the superstiff wire to straighten the iliac artery on the left. This allowed for tracking of the larger sheath so that a bifurcated device could be completed. This technique may be useful in dealing with extreme iliac tortuosity if one is unable to advance the superstiff wire.
At the Intersection of Principal and Teacher Instructional Leadership: The Case of Donaldson Elementary
Authors: Stoelinga Sara Ray
Published: June 2010

After 2 years of progress, the literacy initiative at Donaldson Elementary faces challenges because of a disagreement between Principal Joanna Jackson and Literacy Coordinator Loretta Sullivan over whether Sullivan’s role should include evaluative classroom observations and whether teachers should be mandated to receive coaching. The case is intended to be used in courses or workshops that focus on the enactment of teacher leadership roles and on the process of developing shared leadership structures in schools.
Does Exercise Benefit Fibromyalgia?
Authors: Terre Lisa
Published: June 2010

This review discusses evidence-based perspectives on the potential benefits of exercise for fibromyalgia. Future directions for inquiry and clinical management also are addressed.
The overactive bladder
Authors: Foon Richard , Drake Marcus J.
Published: June 2010

Urinary urgency and the associated symptoms which comprise overactive bladder are prevalent amongst the general population and adversely affect quality of life. Disease management consists of a sequential series of options starting with behavioural and lifestyle techniques, pharmacological management (antimuscarinics) and, in severe cases, surgical treatment (urinary diversion, neuromodulation, augmentation cystoplasty and detrusor myectomy). There is increasing recognition of pathophysiological mechanisms in the urothelium, interstitial cells and afferent neurons allowing the importance of peripheral integrative interaction to be identified. The hierarchy of the central nervous system control adds additional complexity to understanding the oflower urinary tract function. Some newer methods of treatment include Botulinum toxin A intramural injections, oral beta-3 adrenergic agonists and rho-kinase inhibitors. The lack of a disease generating hypothesis, the lack of animal models for disease and the subjective nature of the central symptom (urgency) still pose considerable theoretical and scientific hurdles that need to be overcome in the treatment of this condition.
Secondary malignancies following radiotherapy for prostate cancer
Authors: Sountoulides Petros , Koletsas Nikolaos , Kikidakis Dimitris , Paschalidis Konstantinos , Sofikitis Nikolaos
Published: June 2010

Human exposure to sources of radiation as well as the use of radiation-derived therapeutic and diagnostic modalities for medical reasons has been ongoing for the last 60 years or so. The carcinogenetic effect of radiation either due to accidental exposure or use of radiation for the treatment of cancer has been undoubtedly proven during the last decades. The role of radiation therapy in the treatment of patients with prostate cancer is constantly increasing as less-invasive treatment modalities are sought for the management of this widely, prevalent disease. Moreover the wide adoption of screening for prostate cancer has led to a decrease in the average age that patients are diagnosed with prostate cancer. Screening has also resulted in the diagnosis of low-grade, less-aggressive prostate cancers which would probably never lead to complications or death from the disease. Radiotherapy for prostate cancer has been linked to the late occurrence of second malignancies both in the true pelvis and outside the targeted area due to low-dose radiation scatter. Secondary malignancies following prostate irradiation include predominantly bladder cancer and, to a lesser extent, colon cancer. Those secondary radiation-induced bladder tumors are usually aggressive and sometimes lethal. Care should be given to the long-term follow up of patients under radiation therapy for prostate cancer, while the indications for its use in certain cases should be reconsidered.
Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia: prevalence and prognostic value
Authors: Abbas Saman , Lugthart Sanne , Kavelaars François G. , Schelen Anita , Koenders Jasper E. , Zeilemaker Annelieke , van Putten Wim J. L. , Rijneveld Anita W. , Löwenberg Bob , Valk Peter J. M.
Published: June 2010

Somatic mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) were recently demonstrated in acute myeloid leukemia (AML), but their prevalence and prognostic impact remain to be explored in large extensively characterized AML series, and also in various other hematologic malignancies. Here, we demonstrate in 893 newly diagnosed cases of AML mutations in the IDH1 (6%) and IDH2 (11%) genes. Moreover, we identified IDH mutations in 2 JAK2 V617F myeloproliferative neoplasias (n = 96), a single case of acute lymphoblastic leukemia (n = 96), and none in chronic myeloid leukemias (n = 81). In AML, IDH1 and IDH2 mutations are more common among AML with normal karyotype and NPM1mutant genotypes. IDH1 mutation status is an unfavorable prognostic factor as regards survival in a composite genotypic subset lacking FLT3ITD and NPM1mutant. Thus, IDH1 and IDH2 mutations are common genetic aberrations in AML, and IDH1 mutations may carry prognostic value in distinct subtypes of AML.
Effect of vascular endothelial growth factor and its receptor KDR on the transendothelial migration and local trafficking of human T cells in vitro and in vivo
Authors: Edelbauer Monika , Datta Dipak , Vos Ingrid H. C. , Basu Aninda , Stack Maria P. , Reinders Marlies E. J. , Sho Masayuki , Calzadilla Katiana , Ganz Peter , Briscoe David M.
Published: June 2010

In these studies, we find that the vascular endothelial growth factor (VEGF) receptor KDR is expressed on subsets of mitogen-activated CD4+ and CD8+ T cells in vitro. We also found that KDR colocalizes with CD3 on mitogen-activated T cells in vitro and on infiltrates within rejecting human allografts in vivo. To evaluate whether VEGF and KDR mediate lymphocyte migration across endothelial cells (ECs), we used an in vitro live-time transmigration model and observed that both anti-VEGF and anti-KDR antibodies inhibit the transmigration of both CD4+ and CD8+ T cells across tumor necrosis factorα (TNFα)–activated, but not unactivated ECs. In addition, we found that interactions among CD4+ or CD8+ T cells and TNFα–activated ECs result in the induction of KDR on each T cell subset, and that KDR-expressing lymphocytes preferentially transmigrate across TNFα–activated ECs. Finally, using a humanized severe combined immunodeficient mouse model of lymphocyte trafficking, we found that KDR-expressing lymphocytes migrate into human skin in vivo, and that migration is reduced in mice treated with a blocking anti-VEGF antibody. These observations demonstrate that induced expression of KDR on subsets of T cells, and locally expressed VEGF, facilitate EC-dependent lymphocyte chemotaxis, and thus, the localization of T cells at sites of inflammation.
Notch1 as a potential therapeutic target in cutaneous T-cell lymphoma
Authors: Kamstrup Maria R. , Gjerdrum Lise Mette Rahbek , Biskup Edyta , Thyssing Lauenborg Britt , Ralfkiaer Elisabeth , Woetmann Anders , Ødum Niels , Gniadecki Robert
Published: June 2010

Deregulation of Notch signaling has been linked to the development of T-cell leukemias and several solid malignancies. Yet, it is unknown whether Notch signaling is involved in the pathogenesis of mycosis fungoides and Sézary syndrome, the most common subtypes of cutaneous T-cell lymphoma. By immunohistochemistry of 40 biopsies taken from skin lesions of mycosis fungoides and Sézary syndrome, we demonstrated prominent expression of Notch1 on tumor cells, especially in the more advanced stages. The γ-secretase inhibitor I blocked Notch signaling and potently induced apoptosis in cell lines derived from mycosis fungoides (MyLa) and Sézary syndrome (SeAx, HuT-78) and in primary leukemic Sézary cells. Specific down-regulation of Notch1 (but not Notch2 and Notch3) by siRNA induced apoptosis in SeAx. The mechanism of apoptosis involved the inhibition of nuclear factor-κB, which is the most important prosurvival pathway in cutaneous T-cell lymphoma. Our data show that Notch is present in cutaneous T-cell lymphoma and that its inhibition may provide a new way to treat cutaneous T-cell lymphoma.
Genomic deletion of the whole IgH 3′ regulatory region (hs3a, hs1,2, hs3b, and hs4) dramatically affects class switch recombination and Ig secretion to all isotypes
Authors: Vincent-Fabert Christelle , Fiancette Remi , Pinaud Eric , Truffinet Véronique , Cogné Nadine , Cogné Michel , Denizot Yves
Published: June 2010

The immunoglobulin heavy chain locus (IgH) undergoes multiple changes along B-cell differentiation. In progenitor B cells, V(D)J assembly allows expression of μ heavy chains. In mature B cells, class switch recombination may replace the expressed constant (C)μ gene with a downstream CH gene. Finally, plasma cell differentiation strongly boosts IgH transcription. How the multiple IgH transcriptional enhancers tune these changes is unclear. Here we demonstrate that deletion of the whole IgH 3′ regulatory region (3′RR) allows normal maturation until the stage of IgM/IgD expressing lymphocytes, but nearly abrogates class switch recombination to all CH genes. Although plasma cell numbers are unaffected, we reveal the role of the 3′RR into the transcriptional burst normally associated with plasma cell differentiation. Our study shows that transcriptional changes and recombinations occurring after antigen-encounter appear mainly controlled by the 3′RR working as a single functional unit.
PKCζ decreases eNOS protein stability via inhibitory phosphorylation of ERK5
Authors: Nigro Patrizia , Abe Jun-ichi , Woo Chang-Hoon , Satoh Kimio , McClain Carolyn , O'Dell Michael R. , Lee Hakjoo , Lim Jae-Hyang , Li Jian-dong , Heo Kyung-Sun , Fujiwara Keigi , Berk Bradford C.
Published: June 2010

PKCζ has emerged as a pathologic mediator of endothelial cell dysfunction, based on its essential role in tumor necrosis factor α (TNFα)–mediated inflammation. In contrast, extracellular signal–regulated kinase 5 (ERK5) function is required for endothelial cell homeostasis as shown by activation of Krüppel-like factor 2 (KLF2), increased endothelial nitric-oxide synthase (eNOS) expression, and inhibition of apoptosis. We hypothesized that protein kinase C ζ (PKCζ) activation by TNFα would inhibit the ERK5/KLF2/eNOS pathway. TNFα inhibited the steady laminar flow–induced eNOS expression, and this effect was reversed by the dominant-negative form of PKCζ (Ad.DN-PKCζ). In addition, ERK5 function was inhibited by either TNFα or the transfection of the catalytic domain of PKCζ. This inhibition was reversed by PKCζ small interfering RNA. PKCζ was found to bind to ERK5 under basal conditions with coimmunoprecipitation and the mammalian 2-hybrid assay. Furthermore, PKCζ phosphorylates ERK5, and mutation analysis showed that the preferred site is S486. Most importantly, we found that the predominant effect of TNFα stimulation of PKCζ was to decrease eNOS protein stability that was recapitulated by transfecting Ad.ERK5S486A mutant. Finally, aortic en face analysis of ERK5/PKCζ activity showed high PKCζ and ERK5 staining in the athero-prone region. Taken together our results show that PKCζ binds and phosphorylates ERK5, thereby decreasing eNOS protein stability and contributing to early events of atherosclerosis.
Telomere dysfunction and fusion during the progression of chronic lymphocytic leukemia: evidence for a telomere crisis
Authors: Lin Thet Thet , Letsolo Boitelo T. , Jones Rhiannon E. , Rowson Jan , Pratt Guy , Hewamana Saman , Fegan Chris , Pepper Chris , Baird Duncan M.
Published: June 2010

We performed single-molecule telomere length and telomere fusion analysis in patients at different stages of chronic lymphocytic leukemia (CLL). Our work identified the shortest telomeres ever recorded in primary human tissue, reinforcing the concept that there is significant cell division in CLL. Furthermore, we provide direct evidence that critical telomere shortening, dysfunction, and fusion contribute to disease progression. The frequency of short telomeres and fusion events increased with advanced disease, but importantly these were also found in a subset of early-stage patient samples, indicating that these events can precede disease progression. Sequence analysis of fusion events isolated from persons with the shortest telomeres revealed limited numbers of repeats at the breakpoint, subtelomeric deletion, and microhomology. Array-comparative genome hybridization analysis of persons displaying evidence of telomere dysfunction revealed large-scale genomic rearrangements that were concentrated in the telomeric regions; this was not observed in samples with longer telomeres. The telomere dynamics observed in CLL B cells were indistinguishable from that observed in cells undergoing crisis in culture after abrogation of the p53 pathway. Taken together, our data support the concept that telomere erosion and subsequent telomere fusion are critical in the progression of CLL and that this paradigm may extend to other malignancies.
Shortcomings in the clinical evaluation of new drugs: acute myeloid leukemia as paradigm
Authors: Walter Roland B. , Appelbaum Frederick R. , Tallman Martin S. , Weiss Noel S. , Larson Richard A. , Estey Elihu H.
Published: June 2010

Drugs introduced over the past 25 years have benefitted many patients with acute myeloid leukemia (AML) and provided cure for some. Still, AML remains difficult to treat, and most patients will eventually die from their disease. Therefore, novel drugs and drug combinations are under intense investigation, and promising results eagerly awaited and embraced. However, drug development is lengthy and costs are staggering. While the phase 1–phase 2–phase 3 sequence of clinical drug testing has remained inviolate for decades, it appears intrinsically inefficient, and scientific flaws have been noted by many authors. Of major concern is the high frequency of false-positive results obtained in phase 2 studies. Here, we review features of phase 2 trials in AML that may contribute to this problem, particularly lack of control groups, patient heterogeneity, selection bias, and choice of end points. Recognizing these problems and challenges should provide us with opportunities to make drug development more efficient and less costly. We also suggest strategies for trial design improvement. Although our focus is on the treatment of AML, the principles that we highlight should be broadly applicable to the evaluation of new treatments for a variety of diseases.
Equivalence of multibreed animal models and hierarchical Bayes analysis for maternally influenced traits
Authors: Munilla Leguizamón Sebastián , Cantet Rodolfo JC
Published: June 2010

Background

It has been argued that multibreed animal models should include a heterogeneous covariance structure. However, the estimation of the (co)variance components is not an easy task, because these parameters can not be factored out from the inverse of the additive genetic covariance matrix. An alternative model, based on the decomposition of the genetic covariance matrix by source of variability, provides a much simpler formulation. In this study, we formalize the equivalence between this alternative model and the one derived from the quantitative genetic theory. Further, we extend the model to include maternal effects and, in order to estimate the (co)variance components, we describe a hierarchical Bayes implementation. Finally, we implement the model to weaning weight data from an Angus × Hereford crossbred experiment.

Methods

Our argument is based on redefining the vectors of breeding values by breed origin such that they do not include individuals with null contributions. Next, we define matrices that retrieve the null-row and the null-column pattern and, by means of appropriate algebraic operations, we demonstrate the equivalence. The extension to include maternal effects and the estimation of the (co)variance components through the hierarchical Bayes analysis are then straightforward. A FORTRAN 90 Gibbs sampler was specifically programmed and executed to estimate the (co)variance components of the Angus × Hereford population.

Results

In general, genetic (co)variance components showed marginal posterior densities with a high degree of symmetry, except for the segregation components. Angus and Hereford breeds contributed with 50.26% and 41.73% of the total direct additive variance, and with 23.59% and 59.65% of the total maternal additive variance. In turn, the contribution of the segregation variance was not significant in either case, which suggests that the allelic frequencies in the two parental breeds were similar.

Conclusion

The multibreed maternal animal model introduced in this study simplifies the problem of estimating (co)variance components in the framework of a hierarchical Bayes analysis. Using this approach, we obtained for the first time estimates of the full set of genetic (co)variance components. It would be interesting to assess the performance of the procedure with field data, especially when interbreed information is limited.