bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Lymphocyte Subsets in Patients With Stroke and Their Influence on Infection After Stroke
Authors: Vogelgesang Antje , Grunwald Uwe , Langner Sönke , Jack Robert , Bröker Barbara M. , Kessler Christof , Dressel Alexander
Published: November 2007

Background and Purpose—

Recent studies have attributed the increased infection vulnerability of patients with stroke to stroke-induced immunosuppression. We have therefore explored the immunological changes in patients with ischemic stroke.

Methods—

Blood from 46 patients with stroke was analyzed by fluorescent-activated cell sorter to determine leukocyte subsets. To identify changes that represent clinically relevant immunosuppression, we compared patients who developed infection within 14 days after stroke with those who did not.

Results—

Stroke induced a dramatic and immediate loss of T-lymphocytes, most pronounced within 12 hours after stroke onset. Only patients with subsequent infection exhibited a delay in the recovery of CD4+ T-lymphocyte counts.

Conclusions—

Our data suggest that a loss of CD4+ T cell function contributes to the stroke-induced immunosuppression. The CD4+ T cell count on the day after stroke may emerge as a predictive marker for poststroke infection allowing, early identification of patients at risk.
A Note on Lewicki-Sejnowski Gradient for Learning Overcomplete Representations
Authors: He Zhaoshui , Xie Shengli , Zhang Liqing , Cichocki Andrzej
Published: November 2007

Overcomplete representations have greater robustness in noise environment and also have greater flexibility in matching structure in the data. Lewicki and Sejnowski (2000) proposed an efficient extended natural gradient for learning the overcomplete basis and developed an overcomplete representation approach. However, they derived their gradient by many approximations, and their proof is very complicated. To give a stronger theoretical basis, we provide a brief and more rigorous mathematical proof for this gradient in this note. In addition, we propose a more robust constrained Lewicki-Sejnowski gradient.
See No Evil: Morality and Methodology in Ibn Al-qattān al-Fāsī's Ahkām al-nazar bi-Hāssat al-Basar
Authors: Maghen Ze'ev
Published: November 2007

This essay examines the worldviews underlying, and discursive techniques informing, the jurisprudence of a scholastically unaffiliated and highly original Muslim jurist. It attempts to elucidate the argumentation of a dense and often difficult work, specifically in connection with the twin Qurānic injunctions to "lower one's eyes" (ghadd al-basar) and "guard one's modesty" (hifz al-farj). At the same time, it uses this text as a test case for a preliminary theory of Islamic morality.
"Adversus Infideles": Some Notes On the Cavalier's Tour, the Fleet of the Order of St. John, and the Maltese Corsairs
Authors: Freller Thomas
Published: November 2007

Originally a charitable monastic institution devoted to the care of Christian pilgrims in the Holy Land, the Hospitallers of St. John became a military order during the twelfth century. The arrival of the Order of St. John in Malta in 1530 brought this island to the attention of European leaders and their subjects; indeed, the number of visitors who wrote about their sojourns on the island in the sixteenth and seventeenth centuries is remarkable. At this time private military tours to Malta came to be integrated into what was called the Cavalier's Tour. The famous caravans of the fleet of the Order of St. John played a special role in this development, since participation in the caravans-usually involving naval engagements against the infidel-was considered an integral part of a gentleman's education. The survival of the chivalric Order of St. John seems to testify to the spiritual and cultural continuity of the Crusades up through the period of the Counter Reformation. But closer examination of individual European travelers suggests a rather pragmatic and quite "tolerant" approach to the foreign world. This essay concentratcs on Northern European sources, as it was mainly the Northerners who made the Cavalier's Tour a regular ritual, often entailing the compilation of a detailed travel diary. The accounts of the travelers from Prussia, the Scandinavian countries and central and south Germany show that both Catholics and Protestants alike came to Malta, mainly for reasons of fame, career and the acquisition of military and nautical experience. By the middle of the eighteenth century the Order and its fleet had degenerated to an ornamental show. This decline coincided with the end of the phenomenon dealt with here. In the so-called "Grand Tour" of the second half of the eighteenth century-mostly undertaken by rich Englishmen-there was no space for a trip "adversus infideles." This new type of tour was meant for private pleasure and cultural education. The Ottoman empire was no longer seen as a threat. In contrast to the old emnity, there was a new vogue for things "oriental." The island of Malta and the state of the Knights became an object of curiosity and romantic chivalry.
Pilgrims' Progress: Narratives of Penitence and Reconciliation in the Dutch Reformed Church
Authors: Parker Charles
Published: November 2007

Historians over the past twenty years have utilized consistory records to analyze long-term patterns of illicit behavior and church punishment in Reformed congregations across Europe. Despite the value of these studies, a narrative approach to consistory records offers an opportunity to penetrate the assumptions of local church leaders and to discover real men and women in the sixteenth and seventeenth centuries. Using examples from the pivotal moments in the discipline process in the Dutch Reformed Church at Delft, this article reconstructs the narrative framework of discipline there. The author argues that consistory secretaries recorded discipline cases as ongoing stories of penitence and reconciliation in the lives of all sorts of church members.
'The Armies of the Lord': Christianity, Rebels and the State in Northern Uganda, 1986-1999
Authors: Ward Kevin
Published: November 2007

The accession to power of the National Resistance Movement in Uganda in 1986 was intended to inaugurate a new beginning for Uganda, an end to the political, ethnic and religious divisions that had characterised the country's violent history since the 1960s. Although peace, stability and the strengthening of democratic structures have brought substantial progress to many parts of the country, the Acholi of Northern Uganda have felt largely excluded from these benefits. Violence and insecurity have characterised the districts of Gulu and Kitgum since 1986. It is not simply the failure of development that has been so distressing for the inhabitants, but the collapse of the moral framework and the institutions that gave society coherence. Religion has played a considerable part in articulating the sense of loss and anger at this state of affairs. Traditional Acholi and Christian religious sentiments have helped to shape and sustain rebel movements against the central government, and to inform Acholi responses to the violence inflicted by rebels and government. The article, based on field work conducted in 1999, examines ways in which the main Churches, Catholic and Protestant (Anglican), have historically been bound up with the political divisions of Acholi. It examines the painful adjustments which loss of access to power has necessitated, particularly for the Anglican Church. Since 1986 the Churches have had a vital role in conflict resolution and in envisioning new futures for Acholi. The majority of the population, required to live in 'protected villages', have few material and spiritual resources. The importance of Christian faith and practice for Acholi living in such situations of prolonged conflict, with few signs of speedy resolution, is assessed.
Obadyah the Proselyte and the Roman Liturgy
Authors: Büchler Alfred
Published: November 2007

In his Hebrew autobiography, written probably in the 1120s, the Norman proselyte Obadyah cites in Hebrew transcription the Latin version of a verse taken from the prophet Joel (Masoretic Text: Joel 3:4, Vulgate: Joel 2:31). The verse appears in the first Old Testament reading of the mass of the Saturday after Pentecost, one of the five days of the Roman liturgical year on which the ordination of priests and deacons could take place. It was probably the appearance of Joel's prophecy in this context which imprinted the Latin version in the memory of Obadyah, who had been educated as a cleric, and which made him recall it some twenty years or more after his conversion.
The Golden Mirror in the Imperial Court of the Qianlong Emperor, 1739-1742
Authors: Hanson Marta
Published: November 2007

In the last month of 1739, the third of the Manchu rulers, the Qianlong emperor (r. 1736-1795), ordered the compilation of a treatise on medicine "to rectify medical knowledge" throughout the empire. By the end of 1742, eighty participants chosen from several offices within the palace bureaucracy based in Beijing completed the Golden Mirror of the Orthodox Lineage of Medicine, the only imperially commissioned medical text the Qing government's Imperial Printing Office published. The Golden Mirror represents both the limitations in the power of the Qianlong emperor and the dominance in the Manchu court of Chinese scholarship from the Jiangnan region during the first decade of his reign. Chinese scholars participating in the compilation of the Golden Mirror fashioned a medical orthodoxy for the empire in the mid-eighteenth century from regional trends in scholarship on history and the classics centered in the Jiangnan region since the sixteenth century. The Golden Mirror is an illuminating example of how medical scholars participated in the formation of evidential scholarship in early-modern China and why Manchu patronage, southern Chinese scholarship, and medical orthodoxy coalesced in the imperial court of the Qianlong emperor.
Creating the Future: Apocalyptic Rhetoric in 1 Thessalonians
Authors: Hester James D.
Published: November 2007

Recent studies of apocalyptic literature have brought better definitions of the genre and its worldviews, but have largely ignored issues of argumentation and the nature of apocalyptic discourse. Modern theories of rhetorical criticism help the critic to analyse how that discourse helped the early church to talk about their experiences of persecution and marginality, and how those experiences were to be understood in light of the gospel, which promised that believers were to be with the Lord. In effect apocalyptic discourse helped describe the ethical principles to be followed in daily life and create visions of the future that motivated the believers to practise those principles.
Young Bodies and Religion: Exploring the Role of Religion in Child Abuse
Authors: Botha Pieter J.J.
Published: November 2007

In this article possible connections between religious discourse and child abuse are explored. It would be dangerously naive to consider religion as either irrelevant to or as the cure for the problem of child abuse. The assumption of a direct connection between religion and society is criticised, and a plea is made for rethinking and re-evaluating any straightforward claims for religion promoting moral integrity and providing solutions for child abuse. It is suggested that by considering the complex and indirect interrelationship of religion and mundane, daily life, the involvement of religion in this terrible problem can be dealt with in a more constructive manner and a contribution to a worthwhile turnabout may become possible.
Appropriating Historical Jesus Research in Africa
Authors: Craffert Pieter F.
Published: November 2007

This study starts with a brief overview of the variety of images of Jesus found in African Christianity. African Christianity (like Christianity all over the world) has many ingenious and creative ways of going about the figure of Jesus, of which the quest for what Jesus can do for Africans and the inculturation of Jesus in African images represent the main trends. Although historical Jesus research receives almost no attention in African scholarship, it is argued that a historical understanding of Jesus within his own cultural setting can pick up many clues from the study of religious specialists in African traditional religions (ATRs). From such an approach, Jesus as historical figure can not only be described as similar to typical religious practitioners in many ATRs, but it offers a new avenue for inter-religious dialogue in Africa.
A Contemporary Exegesis At the Edges of Chaos
Authors: Bloomquist L. Gregory
Published: November 2007

Biblical exegesis continues to work under the aegis of assumptions that have been associated with it since the late critical period. I identify primary ones: a posture of objectivity toward the biblical text that purports simply to find in the text what is already there and an approach to the text that abstracts it from the real life experience of human persons. Using socio-rhetorical analysis, I show how ideological analysis undercuts the first assumption, that of passivity toward the text and false modesty toward the exegetical process. Using the same analysis, I show how it is possible to re-enflesh the text to overcome the second problem. This re-enfleshment leads me to reflect on ways that socio-rhetorical analysis accords with contemporary scientific explorations of 'complexity, which emerges on the edge of chaos. I conclude with a call to adopt exegetical practices that can exist on and grow with such a complexity and to see the shortcomings of those practices that adopt an artificial truncation of the process, a truncation that can only be understood as 'death'in contrast with 'life'.
The Competitiveness of the Cuban Tourism Industry in the Twenty-First Century: A Strategic Re-Evaluation
Authors: Miller Mark M. , Henthorne Tony L. , George Babu P.
Published: November 2007

Cuba holds great potential for competitiveness within the Caribbean regional, and even global, tourism industry. The question “Can Cuba realize this potential?” looms increasingly large across the region and within U.S. tourism interests, as Castro's health is in question and brother Raúl assumes more control over the country's political economy. This article analyzes the Cuban tourism industry's current position in the context of leading current models of competitive advantage. It is concluded that, in the case of Cuba, ambitious competitive strategies have been diminished to date by less-focused execution in practice. In general, however, careful analysis of competitive positioning can provide potential for greater success of individual destinations and enhanced regional cooperation.
Sensation Seeking and Its Measurement for Tourism Research
Authors: Litvin Stephen W.
Published: November 2007

Tourism marketers and managers must be sensitive to those psychographic characteristics that distinguish their visitors and potential visitors. A growing list of psychographic characteristics has interested tourism researchers through the years. One such personality trait is the concept of sensation seeking. It is widely accepted that some vacationers seek higher levels of arousal than do others and that the appropriate matching of the trait to the destination or product is an important element of successful tourism marketing. But how does one measure sensation seeking? This article discusses the results of an empirical test that compared a somewhat cumbersome but well-established testing method with a relatively new scale created to serve as an alternative. The findings validate the new, simplified approach.
Changes in Residents' Attitudes toward Tourism over Time: A Cohort Analytical Approach
Authors: Huh Chang , Vogt Christine A.
Published: November 2007

Tourism development in a community must acknowledge residents' attitudes toward and support for tourism as residents are often the business owners, service providers, or workers, and vote on tax millage funding infrastructure investments. Few studies have examined longitudinal changes in hosts' attitudes to tourism. Using a 7-year period and employing a cohort analytical method, residents' attitudes and time-related effects (i.e., age, period, and birth cohort) were studied in an Alaskan island dependent on fishing-related industries with an emerging tourism industry from small cruise ships and outdoor recreation. Constrained multiple regression analyses identified age effect as the dominant variable explaining changes in residents'attitudes toward economic impacts. Successive young adult cohorts were more likely to have favorable attitudes toward tourism's economic impacts. Residents'perceptions of the leading industry (tourism or seafood) in the community, socioeconomic factors, and the effects of age and period explained variations in their attitudes toward tourism over time.
Implementing an Evidence-Based Parenting Program With Adherence in the Real World of Community Practice
Authors: Stern Susan B. , Alaggia Ramona , Watson Katina , Morton Tanya R.
Published: November 2007

This study examined group leaders' adherence to The Incredible Years Parenting Program's components and collaborative process during a yearlong dissemination in a large multicultural city and universal prevention context. Mixed methods were used to evaluate adherence and develop an understanding of the barriers and facilitators of therapist fidelity. Results suggest that the protocol and collaborative group processes were implemented with a high degree of adherence with the three exceptions of role plays, videotape modeling dosage, and “buddy calls.” A number of interconnected barriers with implications for future implementation were identified. Key contributors to adherence included the training and structure of the program, emphasis on accountability and ongoing session monitoring, and important aspects of supervision and group leader qualities.
The Role of Hemodynamic Measurements in the Management of Venous and Ischemic Ulcers
Authors: Lazarides M.K. , Giannoukas A.D.
Published: November 2007

There is a need for quantitative investigations in the vascular laboratory to manage lower extremity ulcers. The majority of leg ulcers are of venous (45%-60%) or arterial origin (10%-20%). Despite the increasing complexity of new devices used in vascular surgical practice, the anklebrachial pressure index (ABPI) remains the cornerstone for the differential diagnosis of ischemic ulcers. The toe-brachial pressure index and the pole test represent attractive alternative tests especially in patients with diabetes. Color flow Doppler imaging (CFDI) is advantageous over ABPI in cases in which wounds and ulcers prevent the use of a cuff by virtue of their size or location; additionally CFDI technology can detect nonflow limiting lesions, lesions to nonaxial arteries such as the deep femoral artery, or lesions limited to a single tibial artery. Continued improvements in the accuracy of CFDI have prompted some vascular surgeons to replace contrast arteriography in distal bypass procedures. Transcutaneous partial oxygen tension measurement (TcPO2) is another noninvasive method that is reliable to select the level of amputation and recommended to determine tissue viability in critically ischemic limbs and in the management of the diabetic foot. CFDI has revolutionized the diagnostic approach to venous disorders and it is considered the gold standard for the assessment of the venous system of the lower limb, causes minimal inconvenience to patients, and is easily repeatable, but it is considered highly operator dependent. Various plethysmography techniques are of limited application in ulcer investigations, because of their difficulty to calibrate signal, unless time measurements such as the postexercise refilling time are used.
A Review of the Clinical Significance of Tissue Hypoxia Measurements in Lower Extremity Wound Management
Authors: Mathieu Daniel , Mani Raj
Published: November 2007

The aim of this paper is to review techniques that are currently available to measure tissue hypoxia in order to benefit the management of wounds. Direct measurement of tissue partial oxygen pressure (PO2) is invasive and therefore unappealing in clinical practice. Several techniques (PET scans, MRI derived techniques) are primarily applicable to research rather than clinical applications. Imaging techniques (duplex ultrasonography, arteriography, MRI techniques) are recommended only as part of the workup for revascularisation. Techniques that assess local perfusion include clearance methods, transcutaneous O2 and CO 2 pressure measurement, and laser Doppler flowmetry and imaging. These techniques permit interpretation of altered perfusion states. Each technique offers subtly different information concerning microvascular function. All these techniques require strict protocols to derive reliable data. The potential of the promising near infrared reflectance spectroscopy (NIRS) technique is yet to be determined.
Studies on the Protective Effects of Boerhaavia diffusa L. Against Gamma Radiation—Induced Damage in Mice
Authors: Manu K.A. , Leyon P.V. , Kuttan Girija
Published: November 2007

The radioprotective effect of the hydro-alcoholic extract of Boerhaavia diffusa was studied using the in vivo mice model. The sublethally irradiated mice (600 rads, single dose) were treated intraperitoneally with 20 mg/kg of the extract. The animals were sacrificed at different time periods after the whole-body radiation. The most affected tissues—bone marrow and intestine—were considerably protected by the intraperitoneal administration of B. diffusa as estimated by bone marrow cellularity, maturing monocytes, and intestinal glutathione. Total white blood cell count was lowered drastically after radiation exposure (ninth day, 1500 ± 500 cells/ mm3). When the animals were exposed to radiation and treated with B. diffusa, the total white blood cell count was lowered only to 4000 ± 400 cells/mm3 on the third day, and it reached an almost normal level (6250 ± 470 cells/mm 3) by the ninth day. The elevated level of serum and liver alkaline phosphatase after radiation exposure was reduced in the B. diffusa—treated group. The serum and liver glutamate pyruvate transferase, which were elevated after radiation exposure, were also reduced by treatment with B. diffusa compared to the control. The lipid peroxidation level also increased in the irradiated animals both in the liver and serum, but in B. diffusa —treated animals, there was a significant reduction in lipid peroxidation levels. The agarose gel electrophoresis of DNA isolated from bone marrow of mice exposed to gamma radiation showed heavy damage that was reduced by treatment with B. diffusa. These results are indicative of the radioprotective effect of the whole-plant extract of B. diffusa.
Integrating Qualitative and Quantitative Methods for Organizational Diagnosis
Authors: Vitale Dean C. , Armenakis Achilles A. , Feild Hubert S.
Published: November 2007

This study reviews considerations for integrating closed-ended items and open-ended questions in a single survey instrument, focusing on contextual effects as a potential pitfall in organizational diagnosis. A randomized posttest-only control group experiment was conducted in a field setting with a small (92 employees) for-profit firm wherein the experimental group received a mixed questionnaire (closed-ended, followed by open-ended, questions) and the control group received only open-ended questions. Individuals receiving the mixed survey responded with a lower response rate and fewer comments than those receiving only the open-ended questions. A thematic content analysis of responses revealed a practically significant difference between groups in respondents' perceptions of the organization's strengths. However, the reported weaknesses of the organization did not differ between groups.
Determination of the Diffusivity of a Hydrophilic Migratory Additive in Ipp Films
Authors: Siqiang Zhu  , Welsh Noah , Hirt Douglas E.
Published: November 2007

This article describes the measurement of the diffusivity of a commercial hydrophilic additive (CHA), Irgasurf HL560, at concentrations of 5 and 10 wt% in polypropylene films at different temperatures. The model used was a standard 1-D diffusion model, in which the film weight was expressed as a function of time as the additive concentration at the film surface was kept at zero at all times. Experimentally, two cases were compared: (1) Washing additive off the film surface with limited contact with the solvent, while PP films were stored in air and tested at 25, 40, 55, and 70°C up to 20 days. (2) Immersing the film in solvent with continuous stirring at 25°C for 10 days, 44°C for 2 days, and 65°C for 10 h. Diffusivity measured by the surface-washing method was 10-14 to 10-12 cm2/s, and 10 -12 to 10-10 by the immersion method. TGA results showed no effect of solvent enhancement to additive diffusion at 25°C but slightly enhanced at 44 and 65°C. Results for both the surface-washing and immersion methods are shown for instructive purposes. It is clear that the diffusivity calculated from surface-washing is much lower than from continuous immersion, largely because the boundary condition of zero additive concentration of the film surfaces was invalid between washings as additive bloomed to the surfaces and accumulated there. The continuous immersion method more closely matched the zero boundary condition used in the model and thus gave more accurate diffusivity values than did the surface-washing method.
Effect of Rheological Strain Hardening on Extrusion Blown Film of Polyvinylidene Fluoride
Authors: Mekhilef Nafaa , Hedhli Lotfi , Moyses Stephan
Published: November 2007

In this work the effect of strain hardening on poly-vinylidene fluoride (PVDF) extrusion blown film is investigated. Controlled long chain branching is introduced via a multi-functional initiator to produce two PVDF samples with different molecular weight and chain architecture. The branched samples are compared to two reference resins having identical molecular weight and no chain branching. All samples are characterized by size exclusion chromatography (SEC) coupled with triple detection system comprising a Differential Refractive Index (DRI) detector, Intrinsic Viscosity (IV) detector, and Multi-Angle Laser Light Scattering (MALLS) detector, to determine their molecular weights and their distribution as well as to detect chain branching via measuring the coil size in dilute solution. The rheological properties are determined using oscillatory measurement and melt strength at 230°C while extensional viscosity measurements are conducted at 180°C to determine strain hardening at different extension rates. The resins are evaluated using a small scale extrusion blown film set-up to determine the blow-up ratio and the minimum thickness achievable. The characterization results show that the control samples are different in molecular weight and almost identical in the polydispersity index (Mw/Mn). The branched samples, however, have higher molecular weight and a slightly broader molecular weight distribution. Light scattering data together with inherent viscosity data show that the branched samples have a lower radius of gyration (RG) and inherent viscosity (IV) over the entire molecular weight distribution confirming chain branching. The rheological properties in oscillatory measurements show that the branched samples exhibit almost identical viscosities as the control samples. However, a broader transition from the Newtonian to the non-Newtonian region for the branched sample is observed confirming the SEC—MALLS results. This is corroborated using extensional viscosity and melt strength measurements, which show a significant strain hardening and an increase in melt strength, respectively. Blown film experiments show that the samples containing chain branching could be processed under similar process conditions as the control samples, and with a higher blow up ratio thereby achieving 5 μm film thickness with high clarity.
Nucleation and Spherulitic Growth Rates in Thin Films With Embedded Thermocouples
Authors: Patki Rahul , Phillips P.J.
Published: November 2007

Fine bare wire thermocouples (12.5 and 25 μm) embedded in polymer films have been used to generate cooling curves in a series of studies, reported earlier, involving crystallization at cooling rates as high as 2000°/min and comparable to those used in film manufacture in industry. The rapid cooling method has resulted in the extension of basic studies of crystallization to supercoolings previously inaccessible using existing methods. The results have been very enlightening and have verified existing theories, but have also generated unique information and heretofore unobserved significant changes in behavior of several polymers. The most startling result is the conclusion that the growth face of a crystal is at a higher temperature than any temperature that can be measured, thus raising serious questions regarding the interpretation of experimental data. The current study investigates the effects of embedding thermocouples in thin films of linear polyethylene on the nucleation and growth rates of spherulites in close proximity. Row nucleation is observed along the surface of the thermocouple, with lamellae growing preferentially perpendicular to the thermocouple axis. When growth rates of spherulites are plotted against spatial distance from the thermocouple, a sigmoidal dependence is observed. The distance at which the growth rate becomes independent of proximity to the thermocouple, or in other words, the width of the `characteristic zone of influence' is found to be a function of thermocouple size and cooling rate. The most remarkable finding is that spherulites growing within this characteristic zone displayed asymmetry in growth rates with radial direction. Consequently, the spherulites exhibit ellipsoidal or irregular shapes and orientation depending on the applied cooling rate. Two independent, albeit simultaneously occurring phenomena are identified to explain the observed behavior: (i) induced mechanical stress, that affects the overall orientation of the spherulites with respect to the thermocouple axis, and (ii) thermal gradient introduced by the heat conduction effect of the thermocouple. However, the relative contribution of these two factors is a function of the applied cooling rate; the behavior being dominated by stress under rapid cooling conditions, whereas the thermal gradient governed the behavior in slow cooling.
ZAP-70 enhances IgM signaling independent of its kinase activity in chronic lymphocytic leukemia
Authors: Chen Liguang , Huynh Lang , Apgar John , Tang Li , Rassenti Laura , Weiss Arthur , Kipps Thomas J.
Published: November 2007

We transduced chronic lymphocytic leukemia (CLL) cells lacking ZAP-70 with vectors encoding ZAP-70 or various mutant forms of ZAP-70 and monitored the response of transduced CLL cells to treatment with F(ab)2 anti-IgM (anti-μ). CLL cells made to express ZAP-70, a kinase-defective ZAP-70 (ZAP-70-KA369), or a ZAP-70 unable to bind c-Cbl (ZAP-YF292) experienced greater intracellular calcium flux and had greater increases in the levels of phosphorylated p72Syk, B-cell linker protein (BLNK), and phospholipase C-γ, and greater activation of the Ig accessory molecule CD79b in response to treatment with anti-μ than did mock-transfected CLL cells lacking ZAP-70. Transfection of CLL cells with vectors encoding truncated forms of ZAP-70 revealed that the SH2 domain, but not the SH1 domain, was necessary to enhance intracellular calcium flux in response to treatment with anti-μ. We conclude that ZAP-70 most likely acts as an adapter protein that facilitates B-cell receptor (BCR) signaling in CLL cells independent of its tyrosine kinase activity or its ability to interact with c-Cbl.
Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia
Authors: le Coutre Philipp , Ottmann Oliver G. , Giles Francis , Kim Dong-Wook , Cortes Jorge , Gattermann Norbert , Apperley Jane F. , Larson Richard A. , Abruzzese Elisabetta , O'Brien Stephen G. , Kuliczkowski Kazimierz , Hochhaus Andreas , Mahon Francois-Xavier , Saglio Giuseppe , Gobbi Marco , Kwong Yok-Lam , Baccarani Michele , Hughes Timothy , Martinelli Giovanni , Radich Jerald P. , Zheng Ming , Shou Yaping , Kantarjian Hagop
Published: November 2007

Patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia (CML-AP) have very limited therapeutic options. Nilotinib is a highly selective BCR-ABL tyrosine kinase inhibitor. This phase 2 trial was designed to characterize the efficacy and safety of nilotinib (400 mg twice daily) in this patient population with hematologic response (HR) as primary efficacy endpoint. A total of 119 patients were enrolled and had a median duration of treatment of 202 days (range, 2–611 days). An HR was observed in 56 patients (47%; 95% confidence interval [CI], 38%-56%). Major cytogenetic response (MCyR) was observed in 35 patients (29%; 95% CI, 21%-39%). The median duration of HR has not been reached. Overall survival rate among the 119 patients after 12 months of follow-up was 79% (95% CI, 70%-87%). Nonhematologic adverse events were mostly mild to moderate. Severe peripheral edema and pleural effusions were not observed. The most common grade 3 or higher hematologic adverse events were thrombocytopenia (35%) and neutropenia (21%). Grade 3 or higher bilirubin and lipase elevations occurred in 9% and 18% of patients, respectively, resulting in treatment discontinuation in one patient. In conclusion, nilotinib is an effective and well-tolerated treatment in imatinib-resistant and -intolerant CML-AP. This trial is registered at www.clinicaltrials.gov as NCT00384228.
Olanzapine and risperidone prescriptions for people with dementia in care
Authors: Malone Darren , Bradley Paul , Lindesay James
Published: November 2007

AIMS AND METHOD

To determine what has happened to care home residents with dementia who were on risperidone or olanzapine prior to the Committee on the Safety of Medicines (CSM) guidance, and to compare with a previous audit of the practice within a community mental health team (CMHT) for older people. Residents with dementia were identified from 10 randomly selected care homes in Leicestershire, and prescriptions before and 9 months after the CSM guidance were assessed. Carers were interviewed to determine who was reviewing residents and how often a review occurred.

RESULTS

In total, 330 residents' medication charts were assessed; 164 (50%) had documentation which identified them as having a dementia; 75 of these residents with dementia (46%) were on an antipsychotic at some time during the audit period. Before CSM advice 69% (37 out of 54) of the antipsychotics prescribed to residents with dementia were either risperidone or olanzapine; this reduced to 39% (19 out of 49) after the CSM advice. Out of those who continued on risperidone or olanzapine, the majority were under GP care only (15 out of 19) and overwhelmingly seen on an as-required basis and infrequently. In two-thirds of cases the prescriptions for antipsychotics were for behavioural and psychological symptoms of dementia. Compared with the CMHT for older people, primary care was less successful at withdrawing risperidone or olanzapine.

CLINICAL IMPLICATIONS

Further research is needed to clarify what approach would be most acceptable and cost-effective to assist British GPs in the management of this patient population.
The ability of adolescent psychiatric units to accept emergency admissions: changes in England and Wales between 2000 and 2005
Authors: Cotgrove Andrew J. , McLoughlin Rachel , O'Herlihy Anne , Lelliott Paul
Published: November 2007

AIMS AND METHOD

The lead consultants of all adolescent in-patient psychiatric units in England and Wales were surveyed in 2000 and again in 2005, to determine whether they could admit young people in an emergency.

RESULTS

In 2000, 51 of 64, and in 2005, 70 of 79 units responded. Although the number of units with dedicated ‘emergency admission beds’ had increased from 6 to 16, 34% of the total could never admit as an emergency in 2005 and 44% could never admit out of hours. The consultants estimated that, in 2005, they turned away 72% of referrals for emergency admission. Although 87% of consultants agreed that there should be emergency access to specialist adolescent psychiatric beds, concern was expressed that services are not configured to accept emergency admissions.

CLINICAL IMPLICATIONS

This problem is unlikely to be resolved by requiring units to accept both emergency and planned admissions. These groups have very different needs. Coherent and unified commissioning is needed to achieve equity of access to emergency beds, along with separate planned admission units and a range of alternative emergency services.
Conditional Expression of a Gi-Coupled Receptor in Osteoblasts Results in Trabecular Osteopenia
Authors: Peng J. , Bencsik M. , Louie A. , Lu W. , Millard S. , Nguyen P. , Burghardt A. , Majumdar S. , Wronski T. J. , Halloran B. , Conklin B. R. , Nissenson R. A.
Published: November 2007

G protein-coupled receptors (GPCRs) coupled to activation of Gs, such as the PTH1 receptor (PTH1R), have long been known to regulate skeletal function and homeostasis. However, the role of GPCRs coupled to other G proteins such as Gi is not well established. We used the tet-off system to regulate the expression of an activated Gi-coupled GPCR (Ro1) in osteoblasts in vivo. Skeletal phenotypes were assessed in mice expressing Ro1 from conception, from late stages of embryogenesis, and after weaning. Long bones were assessed histologically and by microcomputed tomography. Expression of Ro1 from conception resulted in neonatal lethality that was associated with reduced bone mineralization. Expression of Ro1 starting at late embryogenesis resulted in a severe trabecular bone deficit at 12 wk of age (>51% reduction in trabecular bone volume fraction in the proximal tibia compared with sex-matched control littermates; n = 11; P < 0.01). Ro1 expression for 8 wk beginning at 4 wk of age resulted in a more than 20% reduction in trabecular bone volume fraction compared with sex-matched control littermates (n = 16; P < 0.01). Bone histomorphometry revealed that Ro1 expression is associated with reduced rates of bone formation and mineral apposition without a significant change in osteoblast or osteoclast surface. Our results indicate that signaling by a Gi-coupled GPCR in osteoblasts leads to osteopenia resulting from a reduction in trabecular bone formation. The severity of the phenotype is related to the timing and duration of Ro1 expression during growth and development. The skeletal phenotype in Ro1 mice bears some similarity to that produced by knockout of Gs-α expression in osteoblasts and thus may be due at least in part to Gi-mediated inhibition of adenylyl cyclase.
Osteopontin Expression in Human and Murine Obesity: Extensive Local Up-Regulation in Adipose Tissue but Minimal Systemic Alterations
Authors: Kiefer Florian W. , Zeyda Maximilian , Todoric Jelena , Huber Joakim , Geyeregger René , Weichhart Thomas , Aszmann Oskar , Ludvik Bernhard , Silberhumer Gerd R. , Prager Gerhard , Stulnig Thomas M.
Published: November 2007

Obesity is associated with a chronic low-grade inflammation characterized by macrophage infiltration of adipose tissue (AT) that may underlie the development of insulin resistance and type 2 diabetes. Osteopontin (OPN) is a multifunctional protein involved in various inflammatory processes, cell migration, and tissue remodeling. Because these processes occur in the AT of obese patients, we studied in detail the regulation of OPN expression in human and murine obesity. The study included 20 morbidly obese patients and 20 age- and sex-matched control subjects, as well as two models (diet-induced and genetic) of murine obesity. In high-fat diet-induced and genetically obese mice, OPN expression was drastically up-regulated in AT (40 and 80-fold, respectively) but remained largely unaltered in liver (<2-fold). Moreover, OPN plasma concentrations remained unchanged in both murine models of obesity, suggesting a particular local but not systemic importance for OPN. OPN expression was strongly elevated also in the AT of obese patients compared with lean subjects in both omental and sc AT. In addition, we detected three OPN isoforms to be expressed in human AT and, strikingly, an obesity induced alteration of the OPN isoform expression pattern. Analysis of AT cellular fractions revealed that OPN is exceptionally highly expressed in AT macrophages in humans and mice. Moreover, OPN expression in AT macrophages was strongly up-regulated by obesity. In conclusion, our data point toward a specific local role of OPN in obese AT. Therefore, OPN could be a critical regulator in obesity induced AT inflammation and insulin resistance.
Phenotypic plasticity in female naked mole-rats after removal from reproductive suppression
Authors: Dengler-Crish Christine M. , Catania Kenneth C.
Published: November 2007

Naked mole-rats are fossorial African rodents that live in large, eusocial groups. Adult subordinate female mole-rats are reproductively suppressed by the dominant breeding female in their colonies. As a result, subordinate females remain reproductively quiescent for their entire lives unless they are removed from the suppressive presence of the dominant female. This makes subordinate female mole-rats a tractable model for studying phenotypic plasticity. We measured skeletal growth of subordinate, suppressed females as they changed reproductive status. After housing subordinate female mole-rats separately from their home colonies, these animals experienced a growth surge that dramatically increased their body mass and length. After removal from reproductive suppression, females showed an 82% increase in body mass and a 37% increase in the length of their lumbar spines. The lumbar vertebrae were the only skeletal structures that exhibited this puberty-like growth. After colony separation, body mass and lumbar vertebrae growth rates peaked and remained elevated for several weeks before returning to control levels –suggestive of a puberty-like `growth spurt'. Although previous studies have characterized pregnancy-induced lumbar spine elongation in female mole-rats,we demonstrate a significant change in the body morphology of female mole-rats after removal from reproductive suppression but before the first pregnancy.
Nitrergic modulation of an oviposition digging rhythm in locusts
Authors: Newland Philip L. , Yates Paul
Published: November 2007

In locusts, a central pattern generator underlies the rhythmic movements of the ovipositor valves that serve to drive the abdomen into damp soil in order to lay eggs. We have investigated the role of nitric oxide (NO) in the control of this oviposition digging rhythm. NO increases the frequency of the rhythm by acting via sGC to elevate cGMP, which in turn acts viaPKG. Increasing exogenous NO levels using the NO donors SNAP and PAPANONOate increased the cycle frequency of the fictive digging rhythm, as did increasing endogenous NO by bath application of the substrate for NOS, l-arginine. On the other hand, application of the NO scavenger PTIO decreased the cycle frequency, indicating that NO must normally exert a continuous and dynamic role on the central pattern generator underlying the oviposition rhythm. Inhibiting the main molecular target of NO, soluble guanylate cyclase, with ODQ reduced the cycle frequency of the rhythm,suggesting that NO mediated its effects via sGC and cyclic GMP. Further evidence for this was produced by bath application of 8-Br-cGMP, which increased the frequency of the rhythm. Bath application of the generic protein kinase inhibitor and a selective PKG inhibitor, H-7 and KT-5823, respectively,reduced the frequency of the rhythm, suggesting that PKG acted as a target for cGMP. Thus, we conclude that NO plays a key role in regulating the frequency of the central pattern generator controlling rhythmic egg-laying movements in locusts by acting via sGC/cGMP–PKG.
Octopamine partially restores walking in hypokinetic cockroaches stung by the parasitoid waspAmpulex compressa
Authors: Rosenberg Lior Ann , Glusman Jose Gustavo , Libersat Frederic
Published: November 2007

When stung by the parasitoid wasp Ampulex compressa, cockroaches Periplaneta americana enter a hypokinetic state that is characterized by little, if any, spontaneous locomotor activity. In the present study we investigate the effect of an octopamine receptor agonist and an antagonist on the locomotor behavior of stung and control cockroaches. We show that in cockroaches stung by a wasp the octopamine receptor agonist chlordimeform induces a significant increase in spontaneous walking. In good agreement, in control individuals an octopamine receptor antagonist significantly reduces walking activity. Adipokinetic hormone I (AKH-I) promotes spontaneous walking in controls but does not do so in stung individuals, which suggests that the venom effect is most probably not mediated by AKH-I. Dopamine receptor agonists or antagonists had no significant effect on the spontaneous walking of stung or control cockroaches, respectively. The effect of the octopamine receptor agonist was maximal when injected into the brain, suggesting that the wasp venom interferes with octopaminergic modulation of walking initiation in central structures of the cockroach brain.
Returning on empty: extreme blood O2 depletion underlies dive capacity of emperor penguins
Authors: Ponganis P. J. , Stockard T. K. , Meir J. U. , Williams C. L. , Ponganis K. V. , van Dam R. P. , Howard R.
Published: November 2007

Blood gas analyses from emperor penguins (Aptenodytes forsteri) at rest, and intravascular PO2 profiles from free-diving birds were obtained in order to examine hypoxemic tolerance and utilization of the blood O2 store during dives. Analysis of blood samples from penguins at rest revealed arterial PO2s and O2 contents of 68±7 mmHg (1 mmHg= 133.3 Pa) and 22.5±1.3 ml O2dl–1 (N=3) and venous values of 41±10 mmHg and 17.4±2.9 ml O2 dl–1 (N=9). Corresponding arterial and venous Hb saturations for a hemoglobin (Hb)concentration of 18 g dl–1 were >91% and 70%,respectively. Analysis of PO2 profiles obtained from birds equipped with intravascular PO2electrodes and backpack recorders during dives revealed that (1) the decline of the final blood PO2 of a dive in relation to dive duration was variable, (2) final venous PO2 values spanned a 40-mmHg range at the previously measured aerobic dive limit (ADL; dive duration associated with onset of post-dive blood lactate accumulation), (3) final arterial, venous and previously measured air sac PO2 values were indistinguishable in longer dives, and (4) final venous PO2 values of longer dives were as low as 1–6 mmHg during dives. Although blood O2 is not depleted at the ADL, nearly complete depletion of the blood O2 store occurs in longer dives. This extreme hypoxemic tolerance, which would be catastrophic in many birds and mammals, necessitates biochemical and molecular adaptations,including a shift in the O2–Hb dissociation curve of the emperor penguin in comparison to those of most birds. A relatively higher-affinity Hb is consistent with blood PO2values and O2 contents of penguins at rest.