bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and functional patterns of bacterial communities in response to protist predation along an experimental productivity gradient
Authors: Corno Gianluca , Jürgens Klaus
Published: August 2008

Substrate supply and protist grazing are two of the most important forces that determine the composition and properties of bacterial assemblages. General ecological theory predicts that the relative importance of these factors is changing with the environmental productivity. In the present study, the interplay between bottom‐up and top‐down control was studied in a productivity gradient simulated in one‐stage chemostats containing natural assemblages of freshwater bacteria and heterotrophic nanoflagellates. Bacterial assemblages in the chemostats differed strongly with respect to their morphological, physiological and compositional properties in the presence versus the absence of predators. However, theses differences were modified by the productivity gradient. Whereas in predator‐free chemostats the mean abundance and biomass of bacteria increased proportionally with increasing substrate supply, in treatments that included flagellates bacterial production was largely channelled into predator biomass. The bacterial morphological diversity increased along the productivity gradient with increasing substrate input but even more so with predators. Proportional to the increasing substrate supply, predation shifted the remaining bacteria towards morphologically inedible forms. Predation also caused shifts in bacterial substrate‐utilization profiles, and in bacterial community composition, as analysed by terminal restriction fragment length polymorphism of PCR‐amplified 16S‐rRNA genes. Without predators, bacterial richness increased along the productivity gradient whereas with predators bacterial richness was higher at intermediate substrate levels. In accordance with ecological theory, these results demonstrated that predators influence all of the major characteristics of bacterial assemblages but the magnitude of this effect is modulated by the productivity of the system.
Erectile haemodynamic status after radical prostatectomy correlates with erectile functional outcome
Authors: Ohebshalom Michael , Parker Marilyn , Waters Bedford , Flanagan Robert , Mulhall John P.
Published: August 2008

OBJECTIVE

To define haemodynamic changes after radical retropubic prostatectomy (RP) and the predictive value of these for the outcome of erectile function (EF), as although there are predictors of the recovery of EF, penile vascular changes might also affect the recovery of EF.

PATIENTS AND METHODS

Prospective data were analysed from men who had RP followed by duplex penile Doppler ultrasonography (DUS) within 6 months of RP. All men had functional erections before RP, based on self‐report and partner corroboration, and all completed the International Index of Erectile Function (IIEF) questionnaire serially after RP. The EF, based on IIEF scores, was then correlated with the penile DUS results.

RESULTS

In all, the study included 111 patients; 32 (29%) had normal erectile haemodynamics after RP, while 79 (71%) had abnormal haemodynamics. Twelve patients (11%) had a venous leak. There were no differences in mean patient age or comorbidity profile between those with and without haemodynamic changes. Comparing those with normal and abnormal haemodynamics, the mean IIEF EF domain scores were 25 and 17 (P = 0.025), the percentages of erectile rigidity at 18 months was 66% vs 35% (P = 0.013), the percentage of patients with normal EF domain scores was 28% vs 6% (P < 0.01), the percentage of patients with functional erections permitting sexual intercourse unassisted by pharmacological agents was 47% vs 22% (P = 0.018), and the percentage of patients responding to sildenafil citrate, as defined by vaginal penetration, was 72% vs 43% (P = 0.03), respectively.

CONCLUSIONS

The results of this prospective study indicate that a patient’s penile vascular status is correlated with their EF after RP.
Laser robotically assisted nerve‐sparing radical prostatectomy: a pilot study of technical feasibility in the canine model
Authors: Gianduzzo Troy , Colombo Jose R. , Haber Georges‐Pascal , Hafron Jason , Magi‐Galluzzi Cristina , Aron Monish , Gill Inderbir S. , Kaouk Jihad H.
Published: August 2008

OBJECTIVES

To examine the feasibility of using laser energy during nerve‐sparing robotically assisted radical prostatectomy (RARP), as the energy sources currently used for haemostasis in RARP adversely affect cavernous nerve function, while clips require application by a skilled assistant, but laser energy potentially allows precise dissection with minimal collateral tissue injury.

MATERIALS AND METHODS

We used laser‐based RARP in 10 dogs, using the da Vinci S system (Intuitive Surgical, Sunnyvale, CA, USA) and a prototype robotic laser instrument. The potassium‐titanyl‐phosphate laser was used for dissection at 2–6 W, with intermittent use of the neodymium‐doped yttrium‐aluminium‐garnet laser at 5 W for coagulating larger vessels. The peak intracavernosal pressure response to nerve stimulation was recorded as a percentage of mean arterial pressure (ICP%MAP) before and after RARP. Five dogs were killed immediately after RARP and five were maintained alive for 72 h; the haemoglobin and haematocrit levels were measured before and after RARP in the latter five dogs.

RESULTS

All 10 procedures were performed solely using laser energy and no additional haemostatic manoeuvres. The median prostate excision time was 65 min. The ICP%MAP before and after RARP (median 98.5% and 77.0%, P = 0.12) were not significantly different; similarly, the respective haemoglobin (median 14.4 vs 12.6 g/dL, P = 0.06) and haematocrit levels (45.1% vs 40.2%, P = 0.06) were not significantly different. Two dogs had catheter‐related complications and one had an anastomotic leak. There were no laser‐related complications or postoperative haemorrhage.

CONCLUSIONS

Laser RARP is feasible in dogs and further assessment is warranted.
Evaluation of a novel precision template‐guided biopsy system for detecting prostate cancer
Authors: Megwalu Ifeanyichukwu I. , Ferguson Genoa G. , Wei John T. , Mouraviev Vladimir , Polascik Thomas J. , Taneja Samir , Black Linda , Andriole Gerald L. , Kibel Adam S.
Published: August 2008

OBJECTIVE

To explore the ability of a novel transrectal ultrasonography (TRUS) device (TargetScanTM, Envisioneering Medical Technologies, St. Louis MO) that creates a three‐dimensional map of the prostate and calculates an optimal biopsy scheme, to accurately sample the prostate and define the true extent of disease, as standard TRUS‐guided prostate biopsy relies on the operator to distribute the biopsy sites, often resulting in under‐ and oversampling regions of the gland.

PATIENTS AND METHODS

In a multicentre retrospective chart review evaluating patients who had a TargetScan prostate biopsy between January 2006 and June 2007, we determined the overall cancer detection rate in all patients and in subgroups based on prostate specific antigen level, digital rectal examination, and indication for biopsy. We assessed the pathological significance of cancer detected, defined as a Gleason score of ≥7, positive margins, extracapsular disease or >20% tumour volume in the prostatectomy specimen. We also evaluated the concordance in Gleason score between the biopsy and prostatectomy specimen.

RESULTS

Cancer was detected in 50 (35.7%) of the 140 patients biopsied, including 39 (47.6%) with no previous biopsies. Of 23 prostatectomy specimens, 20 (87%) had pathologically significant disease. The biopsy predicted the prostatectomy Gleason score in 12 patients (52%), overestimated in two (9%), underestimated in eight (35%), and biopsy Gleason score could not be assigned in one (4%).

CONCLUSIONS

Template‐guided biopsy potentially produces a higher cancer detection rate and more accurate assessment of grade. Prostatectomy specimens did not have a high rate of pathologically insignificant disease.
IN DEFENCE OF METAPHYSICAL ANALYTICITY
Authors: Hofmann Frank , Horvath Joachim
Published: August 2008

According to the so‐called metaphysical conception of analyticity, analytic truths are true in virtue of meaning (or content) alone and independently of (extralinguistic) facts. Quine and Boghossian have tried to present a conclusive argument against the metaphysical conception of analyticity. In effect, they tried to show that the metaphysical conception inevitably leads into a highly implausible view about the truthmakers of analytic truths. We would like to show that their argument fails, since it relies on an ambiguity of the notion of ‘independence of (extralinguistic) facts’. If one distinguishes between variation independence and existence independence, the unwelcome view about the truthmakers of analytic truths no longer follows. Thus, there is at best a challenge, but no conclusive argument. The door to the metaphysical conception of analyticity is still open.1
E‐communication: Strengthening the Ties between Councillors and Citizens in Norwegian Local Government?
Authors: Hanssen Gro Sandkjaer
Published: August 2008

This article examines the extent to which local politicians use digital channels in their contact with citizens and stakeholders, in comparison with traditional forms of communication (i.e. face‐to‐face and telephone contact) and which politicians are using digital channels the most. By analyzing a national survey of municipal politicians and mayors in Norway, findings show that e‐mail has become an important channel of communication between local politicians and citizens, while e‐debates have not. More surprisingly, the digital divides related to age and levels of education, which are reported in other studies, are less obvious in this study. Variations, however, in e‐mail usage do exist in municipal hierarchies; Mayors, more than other politicians, use e‐mail in work‐related communication. The article also discusses whether digital channels are able to transfer the all important ‘local’ tacit knowledge from citizens to local politicians, and concludes that most politicians do not consider e‐mail to be as capable at doing so as the traditional channels. The article indicates that the informality of e‐mail lowers the threshold for contact, increasing the politicians’ knowledge about the experiences, problems and preferences of the citizens, thus broadening their pattern of communication and reaching new interest groups. E‐mail, therefore, seems to increase contact and strengthen the ties between politicians and citizens. Politicians are aware, though, of the relationship between the electorate's lack of Information and Communication Technology (ICT) competence and usage of e‐communication channels, and they stress that their use of digital channels is a supplement to traditional channels – not a replacement.
Body, Soul, and (Holy) Spirit: Karl Barth's Theological Framework for Understanding Human Ontology
Authors: CORTEZ MARC
Published: August 2008

Abstract:  Interpretations of Karl Barth's anthropological ontology are often characterized by significant disagreement as to whether it is best understood in essentially dualist or monist terms. Such arguments are misguided in that they miss the thrust of Barth's argument. This article will show that Barth's christological understanding of the mind–body relationship generates a number of important ontological implications, which can in turn serve as a basis for developing a christologically adequate mind/body theory, but that it does not provide the actual development of such a theory.
The regulation of brood reduction in Booted Eagles Hieraaetus pennatus through habitat heterogeneity
Authors: CASADO EVA , SUÁREZ‐SEOANE SUSANA , LAMELIN JULIEN , FERRER MIGUEL
Published: August 2008

Brood reduction, the death of one or more chicks through siblicide or starvation, can occur through density‐dependence in fecundity. Brood reduction may arise in territorial breeding systems either as a response to a high level of territorial interference in a situation of high density or as a result of habitat heterogeneity. To test the predictions of the two main hypotheses that attempt to explain how density‐dependent fecundity is generated, the Habitat Heterogeneity Hypothesis (HHH) and the Individual Adjustment Hypothesis (IAH), we analysed the relationship between density and fecundity in an expanding population of Booted Eagles in Doñana National Park, Spain, using an 18‐year data series. We also studied the occurrence and frequency of brood reduction in the same Booted Eagle population to appreciate further its effects and the factors that influence its occurrence and frequency. Our results support the HHH in the present situation of high density, as fecundity in the better territories (older and more frequently occupied) was higher than in low quality territories and was not affected by population density in high density periods. Nevertheless, the fecundity of high quality territories was affected (although not significantly) by population density in periods of low density, suggesting that the IAH was supported when only high quality territories were occupied. Older territories were used more frequently and chicks in these areas hatched earlier and suffered lower mortality than in new territories. We found a significant negative relationship between mean fecundity and its skewness, a finding that also supports HHH. During years of food shortage, less frequently occupied territories suffered higher rates of brood reduction. Brood reduction in this Booted Eagle population was a consequence of the heterogeneous structure of the habitat, with some territories having a higher probability of brood reduction than others. Parental nutritional condition did not affect brood reduction. The effect of brood reduction on nestling quality and population dynamics is also discussed.
Children's eating behaviours: the importance of the family setting
Authors: Kime Nicola
Published: August 2008

Childhood obesity has become a major public health challenge. Whilst it is accepted that the aetiology of obesity is complex, there is very little that targets the home environment and specifically looks at the family setting and how this influences children's eating behaviours. This research aimed to redress the balance by alerting people to the importance of the family environment as a contributory factor for childhood obesity. Using a grounded theory approach, ‘Ordering of eating’ highlights the importance of the family setting and demonstrates how micro and macro order influences the development of children's eating behaviours.
Deep Brain Stimulation Devices: A Brief Technical History and Review
Authors: Coffey Robert J.
Published: August 2008

Deep brain stimulation (DBS)—a broadly accepted therapeutic modality with tens of thousands of patients currently implanted—is the application of implantable electrical stimulation devices to treat neurological disorders. Approved indications include involuntary movement disorders; investigational applications include epilepsy, selected psychiatric disorders, and other conditions. DBS differs fundamentally from functional electrical stimulation and sensory prosthetics in that DBS therapies do not substitute for or replace injured tissues, organs, or body functions. DBS—targeted to particular brain nuclei or pathways that are specific for the disorder under treatment—influences brain function and behavioral output in ways that can relieve symptoms and improve the overall functioning of the patient. We will briefly review the history and present status of DBS from a technical and device‐oriented perspective, with an eye toward future advances.
The Benefits and Costs of New Fuels and Engines for Light‐Duty Vehicles in the United States
Authors: Keefe Ryan , Griffin James P. , Graham John D.
Published: August 2008

Rising oil prices and concerns about energy security and climate change are spurring reconsideration of both automobile propulsion systems and the fuels that supply energy to them. In addition to the gasoline internal combustion engine, recent years have seen alternatives develop in the automotive marketplace. Currently, hybrid‐electric vehicles, advanced diesels, and flex‐fuel vehicles running on a high percentage mixture of ethanol and gasoline (E85) are appearing at auto shows and in driveways. We conduct a rigorous benefit‐cost analysis from both the private and societal perspective of the marginal benefits and costs of each technology—using the conventional gasoline engine as a baseline. The private perspective considers only those factors that influence the decisions of individual consumers, while the societal perspective accounts for environmental, energy, and congestion externalities as well. Our analysis illustrates that both hybrids and diesels show promise for particular light‐duty applications (sport utility vehicles and pickup trucks), but that vehicles running continuously on E85 consistently have greater costs than benefits. The results for diesels were particularly robust over a wide range of sensitivity analyses. The results from the societal analysis are qualitatively similar to the private analysis, demonstrating that the most relevant factors to the benefit‐cost calculations are the factors that drive the individual consumer's decision. We conclude with a brief discussion of marketplace and public policy trends that will both illustrate and influence the relative adoption of these alternative technologies in the United States in the coming decade.
Why Do People Vote? A Psychological Analysis of the Causes of Voter Turnout
Authors: Harder Joshua , Krosnick Jon A.
Published: August 2008

A great deal of scholarship has explored why some democratic citizens vote while others do not. This article reviews that literature through a lens presuming that a person's likelihood of turning out on election day is a multiplicative function of his or her ability to vote, her or her motivation to vote, and the difficulty of obtaining the needed information and carrying out the behavior of voting. We conclude that (a) turnout is made more difficult and less likely by onerous registration procedures; (b) turnout is more likely among some demographic groups because of greater motivation or ability or less difficulty; (c) the social setting in which a person lives and the psychological dispositions he or she possesses can affect turnout by shaping motivation, ability, or difficulty; (d) characteristics of a specific electoral contest can inspire or discourage turnout; and (e) canvassing and interviewing people about an election can increase turnout, but preelection polls and election‐day outcome projections do not. Consequently, an individual citizen/s turnout behavior is a joint function of his or her social location, his or her psychological dispositions, the procedures involved in voting, and events that occur at the time of each election.
Beliefs about Deliberation: Personal and Normative Dimensions
Authors: Borgida Eugene , Worth Keilah A. , Lippmann Brad , Ergun Damla , Farr James
Published: August 2008

Democratic deliberative theory has long emphasized the importance of citizen deliberation as a form of political participation and a centrally important component of any vital democracy. Public deliberation and discourse among citizens has been less frequently investigated as a form of political participation than more standard indicators such as voting or volunteering for political organizations. This research examines the extent to which internalized beliefs about deliberation are associated with deliberation outcome measures among a national sample of high school students participating in a year‐long deliberation forum, Project 540. Using a multilevel analysis, the research specifically tested the extent to which scales of personal and normative deliberation beliefs, independently and moderated by Project 540 participation, predict key deliberative outcomes (e.g., civic skills, intention to participate in civic affairs). We find that predeliberation endorsement of both personal and normative beliefs predicts increases in certain positive deliberative outcomes, and that these effects are not moderated by participation in Project 540. The implications of these findings for deliberative democracy theory and for developing effective citizen deliberation forums are discussed.
Administering the Overseas Vote
Authors: Cain Bruce E. , Mac Donald Karin , Murakami Michael H.
Published: August 2008

While there is a growing academic literature about mail‐in ballots, there has been no serious academic research to date on overseas voters, even though the counting of overseas military ballots figured into the 2000 presidential election controversy. The participation of nearly 4 million overseas voters, both civilian and military, is governed by the Uniformed and Overseas Citizens Absentee Voting Act. The authors examine the reported perceptions of military and nonmilitary voters covered by this legislation using two surveys funded by the U.S. Election Assistance Commission, focusing on their perceptions of electronic means of transmitting voting materials. The authors find that civilian overseas citizens have a harder time registering and voting than military overseas citizens; that the key factor is the timely transmission of voting materials; and that, despite privacy concerns, electronic transmission of voting materials is viewed favorably.
Building Capacity in Election Administration: Local Responses to Complexity and Interdependence
Authors: Hale Kathleen , Slaton Christa Daryl
Published: August 2008

Public administration research has identified networks, professionalization, and collaboration with community interests as potential principles by which public organizations can enhance their capacity and effectiveness. This article explores the implementation of these principles by election administrators at the local level, where their ability to conduct elections is the subject of current scrutiny. Findings indicate that election administrators established networks, professional organizations, professionalization requirements and community collaborations prior to the passage of the Help America Vote Act of 2002. Findings also suggest that local election efforts may become more effective as a result of certain provisions of the act that promote centralization and information dissemination. Local election administrators may also continue to build capacity by applying these public administration principles.
Evaluating Administrative Modernization in German Local Governments: Success or Failure of the “New Steering Model”?
Authors: Kuhlmann Sabine , Bogumil Jörg , Grohs Stephan
Published: August 2008

This article evaluates the results and impacts of administrative modernization in Germany after more than 10 years of New Public Management experience, concentrating on the most advanced level of public sector reform: local authorities. Drawing on a broad empirical basis, the authors pursue the following questions: Do “Weber‐ ian” administrative structures and processes continue to characterize the German public sector, or have the reforms left behind lasting traces of a managerial administration? Are local authorities performing better today, and if so, can this be attributed to the New Public Management modernization? The presented results show that no paradigm shift from the “Weberian” bureaucracy to New Public Management has occurred so far. Performance improvements notwithstanding, the new mix of steering instruments causes numerous unintended consequences, causing “Weberian” administration to reemerge.
Deliberative Innovation to Different Effect: Consensus Conferences in Denmark, France, and the United States
Authors: Dryzek John S. , Tucker Aviezer
Published: August 2008

Democratic reformers are attracted by the role that advisory forums composed of lay citizens can play in public consultation on complex policy issues (such as participatory technology assessment). Using a comparative study of consensus conferences on the issue of genetically modified food in Denmark, France, and the United States, the authors show that the potential of such deliberative “mini‐publics” is quite different in different sorts of political system. They attend to the mode of establishment, perceived legitimacy, policy impact, and influence on public debate of the forum in each case. In actively inclusive Denmark,mini‐publics are deployed in integrative fashion; in exclusive France, in managerial fashion; and in the passively inclusive United States, in advocacy fashion. Proponents and practitioners of deliberative participatory reforms should take into account the constraints and opportunities revealed by this analysis and attend to the different roles that mini‐publics might play in different political systems.
Diacylglycerol kinases in immune cell function and self‐tolerance
Authors: Zhong Xiao‐Ping , Guo Rishu , Zhou Houde , Liu Chenghu , Wan Chi‐Keung
Published: August 2008

Summary: Both diacylglycerol (DAG) and phosphatidic acid (PA) are important second messengers involved in signal transduction from many immune cell receptors and can be generated and metabolized through multiple mechanisms. Recent studies indicate that diacylglycerol kinases (DGKs), the enzymes that catalyze phosphorylation of DAG to produce PA, play critical roles in regulating the functions of multiple immune cell lineages. In T cells, two DGK isoforms, α and ζ, inhibit DAG‐mediated signaling following T‐cell receptor engagement and prevent T‐cell hyperactivation. DGK α and ζ synergistically promote T‐cell anergy and are critical for T‐cell tolerence. In mast cells, DGKζ plays differential roles in their activation by promoting degranulation but attenuating cytokine production following engagement of the high affinity receptor for immunoglobulin E. In dendritic cells and macrophages, DGKζ positively regulates Toll‐like receptor‐induced proinflammatory cytokine production through its product PA and is critical for host defense against Toxoplama gondii infection. These studies demonstrate pivotal roles of DGKs in regulating immune cell function by acting both as signal terminator and initiator.
Cell intrinsic mechanisms of T‐cell inhibition and application to cancer therapy
Authors: Peggs Karl S. , Quezada Sergio A. , Allison James P.
Published: August 2008

Summary: Establishing a balance between the rapid generation of effective immunity and the production of overly exuberant or excessively prolonged responses is critical to the maintenance of the equilibrium between health and disease. The preservation of homeostasis and prevention of inappropriate activation of immunity is safeguarded by systems integrating the influences of T‐cell receptor signaling, pro‐inflammatory danger signals, and positive costimulatory signals on the one hand with those of several layers of both cell‐intrinsic and cell‐extrinsic inhibitory checkpoints on the other. Evolution has thus provided an immunological system capable of clearance of pathogens and infected cells but which generally avoids the severe collateral damage that is associated with failure to control immunity. Central tolerance to self‐antigens constitutes the first line of defense against self‐destruction. Because central tolerance mechanisms fail to eliminate all self‐reactive immune effector cells, other immune‐regulating (peripheral tolerance) mechanisms are required to prevent excessive immune responses. Dysfunction of these inhibitory pathways in terms of reduced activity can result in the unmasking of self‐directed responses and a variety of autoimmune morbidities. Conversely, enhanced inhibitory activity can restrict the generation of clinically useful immunity to cancers and to chronic infectious pathogens. This may manifest not only as inhibition of immunity directed towards what are largely aberrantly or overexpressed ‘self’ targets on malignant cells but also additional exaggeration of inhibitory pathway activity mediated via upregulation on tumor cells or stromal tissues of the ligands for inhibitory receptors expressed by lymphocytes. The selective pressures exerted by immuno‐editing will favor the outgrowth of such immuno‐evasive malignant clones. These pathways therefore represent significant hurdles to the generation of therapeutic anti‐cancer responses. The most active of the T‐cell intrinsic inhibitory pathways belong to the immunoglobulin superfamily, which occupies a central importance in the coordination of immune responses. The CD28/cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4):B7‐1/B7‐2 receptor/ligand grouping represents the archetypal example of these immune regulators. Therapies aimed at overcoming these mechanisms of peripheral tolerance, in particular by blocking the inhibitory checkpoints, offer the potential to generate anti‐tumor activity, either as monotherapies or in synergism with other therapies that directly or indirectly enhance presentation of tumor epitopes to the immune system.
Regulation of T‐cell responses by PTEN
Authors: Buckler Jodi L. , Liu Xiaohe , Turka Laurence A.
Published: August 2008

Summary: The phosphoinositide 3‐kinase (PI3K) signaling pathway plays a critical role in the development, activation, and homeostasis of T cells by modulating the expression of survival and mitogenic factors in response to a variety of stimuli. Ligation of the antigen receptor, costimulatory molecules, and cytokine receptors activate PI3K, resulting in the production of the lipid second messenger phosphatidylinositol‐3,4,5‐triphosphate (PIP3). A number of molecules help to regulate the activity of this pathway, including the lipid phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome 10). By limiting the amount of PIP3 available within the cell, PTEN directly opposes PI3K activity and influences the selection of developing thymocytes as well as the activation requirements of mature T cells. T cells with unchecked PI3K activity, as a result of PTEN deficiency, contribute to the development of both autoimmune disease and lymphoma. This review dissects our current understanding of PI3K and PTEN and discusses why appropriate balance of these molecules is necessary to maintain normal T‐cell responses.
The extended human leukocyte receptor complex: diverse ways of modulating immune responses
Authors: Barrow Alexander David , Trowsdale John
Published: August 2008

Summary: The leukocyte receptor complex (LRC) and its extended region comprise a large set of genes encoding immunoglobulin superfamily (IgSF) receptors, interspersed with other loci. Although the external Ig‐like domains of these molecules are related, they have evolved to bind a wide array of different ligands. Comparison of the organization and functions of the different receptors encoded in the LRC provides insight into their roles in immune recognition, their evolution, and their relevance to disease. In addition, these molecules provide classic examples of inhibitory receptors paired, side by side, with activating receptors that couple with adapter proteins, such as DAP12. Some of these activating receptors can be considered as bifunctional sensors that can perceive changes in the state of their ligands that favors an inhibitory rather than activating response, whereas other receptors have evolved different means, acting as transporters or even molecular chaperones to achieve immune repression. We briefly summarize the complement of receptors encoded in this region of chromosome 19 and discuss the many diverse and versatile mechanisms they have evolved to restrain immune responses.
Lymphoid stroma in the initiation and control of immune responses
Authors: Mueller Scott N. , Ahmed Rafi
Published: August 2008

Summary: The lymphoid tissues are characterized by a complex organized architecture that is supported by a network of stromal cells. These stromal cells play many important roles in addition to serving as structural support. Lymphoid stromal cells, including the specialized fibroblastic reticular cells and follicular dendritic cells, express chemokines, cytokines, adhesion molecules, as well as other factors required for the migration, homeostasis, and survival of immune cells. Studies have demonstrated the dynamic role that lymphoid stromal cells and the chemokines they produce play in directing lymphocyte migration within the spleen and lymph nodes. The stromal network may also play roles in influencing antigen presentation, via adherence of antigen‐presenting cells to the network, and cell survival, via provision of survival factors such as interleukin‐7. Recently, we have shown that dramatic changes in lymphoid chemokine expression occur during many immune responses. This can alter the trafficking and localization of immune cells in lymphoid organs and has many implications for the regulation and shut‐down of immune responses. Here we briefly summarize the roles of stromal cells and lymphoid architecture in the control of immune responses.
Regulation of NK cell responsiveness to achieve self‐tolerance and maximal responses to diseased target cells
Authors: Joncker Nathalie T. , Raulet David H.
Published: August 2008

Summary: Inhibitory receptors specific for major histocompatibility complex (MHC) class I molecules govern the capacity of natural killer (NK) cells to attack class I‐deficient cells (‘missing‐self recognition’). These receptors are expressed stochastically, such that the panel of expressed receptors varies between NK cells. This review addresses how the activity of NK cells is coordinated in the face of this variation to achieve a repertoire that is self‐tolerant and optimally reactive with diseased cells. Recent studies show that NK cells arise in normal animals or humans that lack any known inhibitory receptors specific for self‐MHC class I. These NK cells exhibit self‐tolerance and exhibit functional hyporesponsiveness to stimulation through various activating receptors. Evidence suggests that hyporesponsiveness is induced because these NK cells cannot engage inhibitory MHC class I molecules and are therefore persistently over‐stimulated by normal cells in the environment. Finally, we discuss evidence that hyporesponsiveness is a quantitative trait that varies depending on the balance of signals encountered by developing NK cells. Thus, a tuning process determines the functional set‐point of NK cells, providing a basis for discriminating self from missing‐self, and at the same time endowing each NK cell with the highest inherent responsiveness compatible with self‐tolerance.
Putting out the fire: coordinated suppression of the innate and adaptive immune systems by SOCS1 and SOCS3 proteins
Authors: Dimitriou Ioannis D. , Clemenza Liliana , Scotter Andrew J. , Chen Grace , Guerra Fiona M. , Rottapel Robert
Published: August 2008

Summary: The mounting of an effective immune response requires the coordinated function of both the innate and the adaptive arm of the immune system. Cells from both types of immunity respond to antigenic stimuli through a variety of surface and intracellular receptors and produce cytokines that tightly orchestrate the inflammatory response. The operation of feedback control mechanisms that regulate the duration and the amplitude of antigenic and cytokine receptor signaling is therefore required to prevent hyper‐activation of the immune system that could lead to tissue destruction or autoimmunity. Suppressor of cytokine signaling (SOCS) proteins have been identified as a negative feedback loop to cytokine signaling. Recently, the generation of genetically engineered mouse models permitted the evaluation of their function in different processes of the immune responses. In this article, we review new insights into the modular structure of SOCS proteins and the function of SOCS1 and SOCS3 to negatively regulate activation and/or differentiation pathways in macrophages, dendritic cells, and T lymphocytes. Thus, SOCS family proteins are components of an emerging immunoregulatory mechanism that maintains the coordinated balance of both innate and adaptive immune responses.
Regulatory B cells as inhibitors of immune responses and inflammation
Authors: Bouaziz Jean‐David , Yanaba Koichi , Tedder Thomas F.
Published: August 2008

Summary: B cells positively regulate immune responses through antibody production and optimal CD4+ T‐cell activation. However, a specific and functionally important subset of B cells can also negatively regulate immune responses in mouse autoimmunity and inflammation models. The lack or loss of regulatory B cells has been demonstrated by exacerbated symptoms in experimental autoimmune encephalitis, chronic colitis, contact hypersensitivity, collagen‐induced arthritis, and non‐obese diabetic mouse models. Accumulating evidence suggests that B cells exert their regulatory role through the production of interleukin‐10 (IL‐10) by either B‐1, marginal zone (MZ), or transitional 2–MZ precursor B‐cell subsets. We have recently found that IL‐10‐producing regulatory B cells predominantly localize within a rare CD1dhiCD5+ B‐cell subset that shares cell surface markers with both B‐1 and MZ B cells. We have labeled this specific subset of regulatory B cells as B10 cells to highlight that these rare CD1dhiCD5+ B cells only produce IL‐10 and are responsible for most IL‐10 production by B cells and to distinguish them from other regulatory B‐cell subsets that may also exist. This review focuses on the recent progress in this field and the exciting opportunities for understanding how this unique B‐cell subset influences diverse immune functions.
Regulation of hematopoietic cell function by inhibitory immunoglobulin G receptors and their inositol lipid phosphatase effectors
Authors: Cady Carol T. , Rice Jeffrey S. , Ott Vanessa L. , Cambier John C.
Published: August 2008

Summary: Numerous autoimmune and inflammatory disorders stem from the dysregulation of hematopoietic cell activation. The activity of inositol lipid and protein tyrosine phosphatases, and the receptors that recruit them, is critical for prevention of these disorders. Balanced signaling by inhibitory and activating receptors is now recognized to be an important factor in tuning cell function and inflammatory potential. In this review, we provide an overview of current knowledge of membrane proximal events in signaling by inhibitory/regulatory receptors focusing on structural and functional characteristics of receptors and their effectors Src homology 2 (SH2) domain‐containing tyrosine phosphatase 1 and SH2 domain‐containing inositol 5‐phosphatase‐1. We review use of new strategies to identify novel regulatory receptors and effectors. Finally, we discuss complementary actions of paired inhibitory and activating receptors, using FcγRIIA and FcγRIIB regulation human basophil activation as a prototype.
Early Hemoperfusion With a Polymyxin B Column Improves Gastric Intramucosal pH in Sepsis
Authors: Kushi Hidehiko , Miki Takahiro , Sakagami Yuichiro , Sato Jun , Saito Takeshi , Tanjoh Katsuhisa
Published: August 2008

Abstract:  This study had two purposes. One was to assess gastric intramucosal pH (pHi) after early goal‐directed therapy in patients with sepsis and septic shock. The other was to determine whether direct hemoperfusion with a polymyxin B fiber column (DHP‐PMX) could improve the pHi if it remained low after early goal‐directed therapy. The subjects were 32 patients who underwent early goal‐directed therapy within 6 h of a diagnosis of sepsis or septic shock, and who achieved the following conditions: (i) central venous pressure of 8–12 mm Hg; (ii) mean arterial blood pressure ≥65 mm Hg; (iii) urine output ≥0.5 mL/kg/h; and (iv) mixed venous oxygen saturation ≥70%. A gastric tonometer was inserted in each patient and the pHi was measured before DHP‐PMX, and at 24, 48, and 72 h after the start of treatment. The pHi was 7.22 ± 0.04 immediately before DHP‐PMX, 7.28 ± 0.03 (P < 0.05) at 24 h, 7.32 ± 0.03 (P < 0.01) at 48 h, and 7.34 ± 0.02 (P < 0.01) at 72 h, showing a significant increase from 24 h onward compared with the pretreatment value. In patients with sepsis and septic shock, the pHi remained low after early goal‐directed therapy; however, it was significantly improved from 24 h after the start of DHP‐PMX and was normalized from 48 h onwards. These findings suggest that DHP‐PMX improves pHi. Because this was a prospective uncontrolled observational study on a limited number of patients, larger multicenter clinical trials are required to more accurately assess the benefits of DHP‐PMX.
A Case Report of Successful Treatment With Immunoadsorption Onto Protein A in Mixed Connective Tissue Disease in Childhood
Authors: Rummler Silke , Althaus Karina , Maak Bernhard , Barz Dagmar
Published: August 2008

Abstract:  An 11‐year‐old male patient suffering mixed connective tissue disease with life‐threatening pulmonary arterial hypertension, progressive heart failure (New York Heart Association class III–IV), skin ulcers, Raynaud's phenomenon and arthritis, showing no improvement after intensive immunosuppressive therapy or high dose steroids, was treated with immunoadsorption onto protein A. With a combined therapy of low‐dose cortisone and bosentan and 22 sessions of immunoadsorption, his condition improved significantly and he continues in clinical remission. At the time of writing no further immunosuppressive therapy or immunoadsorption had been necessary. The patient is now 15 years old and healthy with an age‐based constitution comparable to the normal population.
Treatment of mild to moderate dehydration in children with oral rehydration therapy
Authors: Diggins Kristene C
Published: August 2008

Purpose: To review current literature on the effectiveness of oral rehydration therapy (ORT) in the treatment of mild to moderate dehydration in children.

Data sources: Recommendations from American Academy of Pediatrics (AAP), World Health Organization (WHO), selected research articles (2000–2006), and Internet sources.

Conclusions: Dehydration is a common diagnosis in pediatric primary care. The literature indicates that dehydration is more often treated with intravenous (IV) therapy when ORT would be equally effective. ORT is an effective treatment for children with mild to moderate dehydration. ORT could be used more frequently rather than IV rehydration therapy. The use of ORT versus traditional methods of IV hydration matches the nursing philosophy of holistic care by enhancing client comfort and autonomy.

Implications for practice: Current practice in the treatment of mild to moderate dehydration in children does not match both AAP and WHO guidelines, which are based on evidence supporting ORT effectiveness. Treatment with ORT allows children more flexibility to be treated at home and thus decreases hospital stay. Evidence shows that the time required to initiate ORT is actually quicker than IV therapy and allows for a less stressful therapy that can be performed in the home.
Caregiver burden among dementia patient caregivers: A review of the literature
Authors: Etters Lynn , Goodall Debbie , Harrison Barbara E.
Published: August 2008

Purpose: To identify current evidence of factors influencing dementia‐related caregiver burden (CB), describe patient and caregiver characteristics associated with CB, and describe evidence‐based interventions designed to lessen the burden of caregiving.

Data sources: Comprehensive literature review of Cumulative Index of Nursing and Allied Health Literature, MEDLINE, and Psych Info was performed for the years 1996–2006 of peer‐reviewed journals using keywords CB and dementia.

Conclusion: Dementia caregiving has been associated with negative effects on caregiver health and early nursing home placement for dementia patients. Many factors influence the impact of the caregiving experience such as gender, relationship to the patient, culture, and personal characteristics. Although various interventions have been developed with the goal of alleviating CB, evidence suggests that individually developed multicomponent interventions including a diversity of services will decrease burden, improve quality of life, and enable caregivers to provide at‐home care for longer periods prior to institutionalization.

Implications for practice: The ability to properly assess the dementia patient–caregiver dyad related to CB is critical to decreasing its negative physical and psychological health outcomes. Appropriately tailored interventions can improve the health and well‐being of both caregiver and patient.
Computed tomography as an aid to management of chronic oropharyngeal stick injury in the dog
Authors: Nicholson I. , Halfacree Z. , Whatmough C. , Mantis P. , Baines S.
Published: August 2008

Objective: To describe the use of computed tomography scanning in the management of dogs with chronic signs after oropharyngeal stick injury.

Methods: Dogs with a final diagnosis of chronic oropharyngeal stick injury that underwent a computed tomography scan during their investigation were selected retrospectively from case files at the Royal Veterinary College, London.

Results: The six dogs were young (median age 3·1 years) and medium to large breed (19·0 to 42·0 kg). By the time of referral the most common clinical sign was cervical swelling (five dogs). Stick foreign bodies were apparent on the plain computed tomography images in all cases and appeared as well‐demarcated, linear abnormalities. A ventral mid‐line approach was used for foreign body retrieval, and the computed tomography findings corresponded well with the surgical findings, with stick foreign body length ranging from 1 to 7 cm. Closed suction drainage was used in five dogs, for two to four days. Clinical signs fully resolved postoperatively in all cases, although cervical swelling recurred three weeks after surgery in one case. This dog had the smallest foreign body, the greatest number of surgical interventions before referral (three) and the longest disease course before referral (eight months).

Clinical Significance: Computed tomography scanning is accurate in identifying the presence and location of chronic stick foreign bodies. Recurrence of disease is possible despite successful retrieval of the wood fragments found by computed tomography scan.
Septic pericardial effusion associated with pulmonary and pericardial botryomycosis in a dog
Authors: Casamián‐Sorrosal D. , Fournier D. , Shippam J. , Woodward B. , Tennant K.
Published: August 2008

The authors report a case of septic pericardial effusion resulting in cardiac tamponade associated with intrathoracic botryomycosis in a dog. Septic pericarditis and a pulmonary mass were diagnosed, and subtotal pericardiectomy and lobectomy of the affected pulmonary areas were carried out. Histopathology of the excised tissue showed changes supportive of botryomycosis – namely a pyogranulomatous inflammation with neutrophils centred around amorphous homogeneous eosinophilic material and club‐like bodies containing Gram‐positive bacterial cocci present in the centre. The patient recovered well following surgery and antibiotic therapy. To the authors’ knowledge, this is the first report of pulmonary botryomycosis in the dog and the first report of this condition presented with pericardial involvement and cardiac tamponade in any species.
Primary pulmonary spindle cell tumour (haemangiopericytoma) in a dog
Authors: Vignoli M. , Buchholz J. , Morandi F. , Laddaga E. , Brunetti B. , Rossi F. , Terragni R. , Sarli G.
Published: August 2008

Haemangiopericytoma is a soft tissue sarcoma believed to originate from pericytes. These tumours are commonly located on the skin and subcutaneous tissue of dogs and are most commonly found on the limbs. To the authors’ knowledge, primary lung haemangiopericytomas have not been previously described in dogs. This case report describes the diagnostic evaluation and treatment of a primary haemangiopericytoma of the lung in a 10‐year‐old male, neutered, Siberian husky dog. Staging of the tumour was performed using a computed tomography scan of the thorax and a computed tomography‐guided fine‐needle aspiration biopsy of the lesion. Treatment was a right caudal lobectomy from a right lateral approach. No regional lymph node changes were noted on computed tomography or intraoperative assessments. Histopathology confirmed a spindle cell tumour that stained positive for vimentin and negative for desmin and S‐100.