bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective Shunting of the NMDA EPSP Component by the Slow Afterhyperpolarization in Rat CA1 Pyramidal Neurons
Authors: Fernández de Sevilla David , Fuenzalida Marco , Porto Pazos Ana B. , Buño Washington
Published: March 2007

Pyramidal neuron dendrites express voltage-gated conductances that control synaptic integration and plasticity, but the contribution of the Ca2+-activated K+-mediated currents to dendritic function is not well understood. Using dendritic and somatic recordings in rat hippocampal CA1 pyramidal neurons in vitro, we analyzed the changes induced by the slow Ca2+-activated K+-mediated afterhyperpolarization (sAHP) generated by bursts of action potentials on excitatory postsynaptic potentials (EPSPs) evoked at the apical dendrites by perforant path-Schaffer collateral stimulation. Both the amplitude and decay time constants of EPSPs (τEPSP) were reduced by the sAHP in somatic recordings. In contrast, the dendritic EPSP amplitude remained unchanged, whereas τEPSP was reduced. Temporal summation was reduced and spatial summation linearized by the sAHP. The amplitude of the isolated N-methyl-d-aspartate component of EPSPs (EPSPNMDA) was reduced, whereas τNMDA was unaffected by the sAHP. In contrast, the sAHP did not modify the amplitude of the isolated EPSPAMPA but reduced τAMPA both in dendritic and somatic recordings. These changes are attributable to a conductance increase that acted mainly via a selective “shunt” of EPSPNMDA because they were absent under voltage clamp, not present with imposed hyperpolarization simulating the sAHP, missing when the sAHP was inhibited with isoproterenol, and reduced under block of EPSPNMDA. EPSPs generated at the basal dendrites were similarly modified by the sAHP, suggesting both a somatic and apical dendritic location of the sAHP channels. Therefore the sAHP may play a decisive role in the dendrites by regulating synaptic efficacy and temporal and spatial summation.
Mixture of Trajectory Models for Neural Decoding of Goal-Directed Movements
Authors: Yu Byron M. , Kemere Caleb , Santhanam Gopal , Afshar Afsheen , Ryu Stephen I. , Meng Teresa H. , Sahani Maneesh , Shenoy Krishna V.
Published: March 2007

Probabilistic decoding techniques have been used successfully to infer time-evolving physical state, such as arm trajectory or the path of a foraging rat, from neural data. A vital element of such decoders is the trajectory model, expressing knowledge about the statistical regularities of the movements. Unfortunately, trajectory models that both 1) accurately describe the movement statistics and 2) admit decoders with relatively low computational demands can be hard to construct. Simple models are computationally inexpensive, but often inaccurate. More complex models may gain accuracy, but at the expense of higher computational cost, hindering their use for real-time decoding. Here, we present a new general approach to defining trajectory models that simultaneously meets both requirements. The core idea is to combine simple trajectory models, each accurate within a limited regime of movement, in a probabilistic mixture of trajectory models (MTM). We demonstrate the utility of the approach by using an MTM decoder to infer goal-directed reaching movements to multiple discrete goals from multi-electrode neural data recorded in monkey motor and premotor cortex. Compared with decoders using simpler trajectory models, the MTM decoder reduced the decoding error by 38 (48) percent in two monkeys using 98 (99) units, without a necessary increase in running time. When available, prior information about the identity of the upcoming reach goal can be incorporated in a principled way, further reducing the decoding error by 20 (11) percent. Taken together, these advances should allow prosthetic cursors or limbs to be moved more accurately toward intended reach goals.
Basement Membrane Remodeling in Skeletal Muscles of Patients with Limb Ischemia Involves Regulation of Matrix Metalloproteinases and Tissue Inhibitor of Matrix Metalloproteinases
Authors: Baum Oliver , Ganster Murielle , Baumgartner Iris , Nieselt Kay , Djonov Valentin
Published: March 2007

Background/Aim: Because the pericapillary basement membrane in skeletal muscles of patients with chronic critical limb ischemia (CLI) is thickened, we determined the expression patterns of genes involved in collagen metabolism, using samples from 9 CLI patients, 4 patients with acute limb ischemia and 4 healthy controls. Methods: Gene array analysis, quantitative RT-PCR and semiquantitative grading of immunohistochemical reactivity were performed to determine mRNA/cDNA and protein concentrations. Results: In CLI patients compared to controls, cDNA levels of matrix metalloproteinase (MMP)-9 and MMP-19 were higher, collagen type IV chains A1 and A2, tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2 were similar and MMP-2 were lower. On the protein level, MMP-2, MMP-9, MMP-19 and TIMP-1 were more abundantly expressed. In skeletal muscles from patients with acute limb ischemia, cDNA and protein levels of MMP-9, MMP-19, collagen type IV chains, TIMP-1 and TIMP-2 were high. MMP-2 was elevated at the protein but decreased on the cDNA level. Conclusion: Expression of basement membrane components in skeletal muscles of CLI and acute limb ischemia patients is altered, possibly contributing to the pathogenesis of peripheral arterial disease.
The Effects of Endothelial Factor Inhibition on the Time Course of Responses of Isolated Rat Coronary Arteries to Intraluminal Flow
Authors: Azzawi May , Austin Clare
Published: March 2007

The aims of this study were to investigate, for the first time, the effects of endothelial factor inhibition on both the magnitude and dynamics of the response of isolated small coronary arteries to intraluminal flow. Isolated rat coronary arteries were mounted on a pressure myograph and left to develop myogenic tone. Flow was introduced and maintained until stable diameters were attained. Dilatory responses were observed which were maximal at low flow rates (5–10 µl/min) and thus shear stresses (1–2 dyn/cm2). These responses were transient in nature. Transient dilations were also observed upon cessation of flow. All responses (to 5 µl/min) were endothelium dependent and were completely abolished by addition of charybdotoxin (100 nM) and apamin (100–500 nM) suggesting an important role for a hyperpolarizing mechanism most likely involving an endothelium-derived hyperpolarizing factor. However, inhibitors of nitric oxide synthase (L-NNA; 100 µM) or cyclo-oxygenase (indomethacin; 10 µM) also modulated the response causing an increase and decrease in maximum vasodilation, respectively. By examining the time course we showed that both agents also made the response significantly more transient in nature. These results show that inhibition of endothelial factor pathways can influence both the magnitude and dynamics of the response of isolated rat coronary arteries to flow.
Overexpression of Angiotensin-Converting Enzyme 2 in the Rostral Ventrolateral Medulla Causes Long-Term Decrease in Blood Pressure in the Spontaneously Hypertensive Rats
Authors: Yamazato Masanobu , Yamazato Yoriko , Sun Chengwen , Diez-Freire Carlos , Raizada Mohan K.
Published: February 2007

The rostral ventrolateral medulla (RVLM) is a relay point that provides supraspinal excitatory input to sympathetic preganglionic neurons in the regulation of blood pressure. The importance of the RVLM is further highlighted by observations that an increase of RVLM sensitivity to angiotensin II and enhanced sympathetic activity are associated with hypertension. Angiotensin-converting enzyme 2 (ACE2) has been shown to be central in maintaining the balance between vasoconstrictor activity of angiotensin II with vasoprotective action of angiotensin-(1-7) in the peripheral system. However, its role in central control of blood pressure in the RVLM is yet to be investigated. Thus, our objective in this study was to compare ACE2 expression in the RVLM of Wistar–Kyoto rats and spontaneously hypertensive rats and to determine whether RVLM ACE2 is involved in blood pressure control. ACE2 immunoreactivity was diffusely distributed in many cardiovascular regulatory neurons, including the RVLM. Western blot analysis revealed a 40% decrease in ACE2 in the RVLM of spontaneously hypertensive rat compared with Wistar–Kyoto rats. Lentiviral-mediated overexpression of ACE2 (lenti-ACE2) was used to determine whether a decrease in ACE2 in the RVLM is associated with hypertensive state. Bilateral injection of lenti-ACE2 resulted in a long-term expression of transgenic ACE2. This was associated with a decrease in mean arterial pressure exclusively in the spontaneously hypertensive rat (141±4 mm Hg in lenti-GFP versus 124±5 mm Hg in lenti-ACE2) and heart rate (304±7 bpm in lenti-GFP versus 285±5 bpm in lenti-ACE2). These observations demonstrate that overexpression of ACE2 overcomes its intrinsic decrease in the RVLM and decreases high blood pressure in the spontaneously hypertensive rat.
Incremental Value of Strain Rate Imaging to Wall Motion Analysis for Prediction of Outcome in Patients Undergoing Dobutamine Stress Echocardiography
Authors: Ingul Charlotte Bjork , Rozis Ellen , Slordahl Stig A. , Marwick Thomas H.
Published: February 2007

Background—

Wall motion score at dobutamine stress echocardiography is an independent predictor of mortality. We sought to determine whether quantification of DSE by strain rate imaging was incremental to wall motion score for predicting outcome.

Methods and Results—

In 646 patients undergoing dobutamine stress echocardiography for the evaluation of known or suspected coronary disease, customized software was used to automatically measure peak systolic strain rate (SR
s
) and end-systolic strain (S
es
) in 18 segments. Results were expressed as the number of abnormal segments and the mean SR
s
and S
es
per patient. All-cause mortality was identified over 7 years of follow-up (mean, 5.2±1.5 years). Contributions of clinical, wall motion, and SR
s
and S
es
data to outcome were analyzed with Cox models, which also were used to define cut points for SR
s
and S
es
. Ischemia (new or worsening wall motion abnormalities) was detected in 45%, and 39% had a previous myocardial infarction. In patients with no ischemia, annualized mortality without and with previous myocardial infarction were 2% and 3% compared with 5% in patients with ischemia. Peak wall motion score index, mean SR
s
, segmental S
es
, and segmental SR
s
were all predictors of mortality, but only segmental SR
s
(hazard ratio, 3.6; 95% CI, 1.7 to 7.2) was independently predictive. In sequential Cox models, the model based on clinical data (overall χ
2
, 12.7) was improved by peak wall motion score index (18.4,
P
=0.002) and further increased by either segmental SR
s
(31.8,
P
<0.001) or mean SR
s
(25.7,
P
=0.009).

Conclusions—

Segmental analysis by SR
s
, derived from automated strain rate imaging analysis of dobutamine stress echocardiography response, offers prognostic information that is independent and incremental to standard wall motion score index.
Targeting Heme-Oxidized Soluble Guanylate Cyclase in Experimental Heart Failure
Authors: Boerrigter Guido , Costello-Boerrigter Lisa C. , Cataliotti Alessandro , Lapp Harald , Stasch Johannes-Peter , Burnett John C.
Published: February 2007

Soluble guanylate cyclase is a heterodimeric enzyme with a prosthetic heme group that, on binding of its main ligand, NO, generates the second messenger cGMP. Unlike conventional nitrovasodilators, the novel direct NO- and heme-independent soluble guanylate cyclase activator BAY 58-2667 is devoid of non-cGMP actions, lacks tolerance development, and preferentially activates NO-insensitive heme-free or oxidized soluble guanylate cyclase. BAY 58-2667, therefore, represents a novel therapeutic advance in mediating vasodilation. To date, its cardiorenal actions in congestive heart failure (CHF) are undefined. We, therefore, hypothesized that BAY 58-2667 would have beneficial preload- and afterload-reducing actions in experimental severe CHF together with renal vasodilating properties. We assessed the cardiorenal actions of intravenous administration of 2 doses of BAY 58-2667 (0.1 and 0.3 μg/kg per minute, respectively) in a model of tachypacing-induced severe CHF. In CHF, BAY 58-2667 dose-dependently reduced mean arterial, right atrial, pulmonary artery, and pulmonary capillary wedge pressure (from baseline 19±1 to 12±2 mm Hg). Cardiac output (2.4±0.3 to 3.2±0.4 L/min) and renal blood flow increased. Glomerular filtration rate and sodium and water excretion were maintained. Consistent with cardiac unloading, atrial and B-type natriuretic peptide decreased. Plasma renin activity (
P
=0.31) and aldosterone remained unchanged (
P
=0.19). In summary, BAY 58-2667 in experimental CHF potently unloaded the heart, increased cardiac output and renal blood flow, and preserved glomerular filtration rate and sodium and water excretion without further neurohumoral activation. These beneficial properties make direct soluble guanylate cyclase stimulation with BAY 58-2667 a promising new therapeutic strategy for cardiovascular diseases, such as heart failure.
Performance Pay System Preferences of Students Preparing to Be Teachers
Authors: Milanowski Anthony
Published: February 2007

This study explored the potential acceptability of performance pay to new teachers by investigating attitudes toward performance pay of students preparing to be teachers. Focus groups and a survey of students preparing to be teachers at a large U.S. university were conducted. Most students expressed a preference for some form of performance pay and tended to prefer pay based on individual performance or pay for knowledge and skill development instead of pay based on school performance. Personality traits and work values were not related to preferences for different performance pay approaches or performance pay in general. These results suggest that teachers' experiences rather than personality or work values may be the dominant influences on attitudes toward performance pay. This implies that beginning teachers may view performance pay more favorably than their more experienced colleagues, suggesting a strategy of applying performance pay to new teachers only.
Private Schools and the Willingness to Pay for Public Schooling
Authors: Brasington David M.
Published: February 2007

Households pay a premium to live in houses assigned to high quality public schools, and the housing market yields information about the demand for public school quality. The current study estimates a two-stage house price hedonic emphasizing the role that private schools play in the willingness to pay for public school quality. The elasticity of house prices with respect to public school quality is 0.15, and 0.04 with respect to private school quality. The price elasticity of demand for public schooling is −1.72, with an income elasticity of 0.31. Public and private schools are substitutes, with a cross-price elasticity of 0.32. A school choice program that reduced private school tuition by 10 percent would reduce the willingness to pay for public school performance by 1.9 percent. The magnitude of the results generally varies markedly between large and small houses, with large houses more responsive to public and private schooling variables.
Influence of Land Cover and Soil Moisture on the Horizontal Distribution of Sensible and Latent Heat Fluxes in Southeast Kansas during IHOP_2002 and CASES-97
Authors: LeMone Margaret A. , Chen Fei , Alfieri Joseph G. , Tewari Mukul , Geerts Bart , Miao Qun , Grossman Robert L. , Coulter Richard L.
Published: February 2007

Analyses of daytime fair-weather aircraft and surface-flux tower data from the May–June 2002 International H2O Project (IHOP_2002) and the April–May 1997 Cooperative Atmosphere Surface Exchange Study (CASES-97) are used to document the role of vegetation, soil moisture, and terrain in determining the horizontal variability of latent heat LE and sensible heat H along a 46-km flight track in southeast Kansas. Combining the two field experiments clearly reveals the strong influence of vegetation cover, with H maxima over sparse/dormant vegetation, and H minima over green vegetation; and, to a lesser extent, LE maxima over green vegetation, and LE minima over sparse/dormant vegetation. If the small number of cases is producing the correct trend, other effects of vegetation and the impact of soil moisture emerge through examining the slope ΔxyLE/ΔxyH for the best-fit straight line for plots of time-averaged LE as a function of time-averaged H over the area. Based on the surface energy balance, H + LE = Rnet − Gsfc, where Rnet is the net radiation and Gsfc is the flux into the soil; Rnet − Gsfc ∼ constant over the area implies an approximately −1 slope. Right after rainfall, H and LE vary too little horizontally to define a slope. After sufficient drying to produce enough horizontal variation to define a slope, a steep (∼−2) slope emerges. The slope becomes shallower and better defined with time as H and LE horizontal variability increases. Similarly, the slope becomes more negative with moister soils. In addition, the slope can change with time of day due to phase differences in H and LE. These trends are based on land surface model (LSM) runs and observations collected under nearly clear skies; the vegetation is unstressed for the days examined. LSM runs suggest terrain may also play a role, but observational support is weak.
Orographic Precipitation and Water Vapor Fractionation over the Southern Andes
Authors: Smith Ronald B. , Evans Jason P.
Published: February 2007

The climatological nature of orographic precipitation in the southern Andes between 40° and 48°S is investigated primarily using stable isotope data from streamwater. In addition, four precipitation events are examined using balloon soundings and satellite images. The Moderate Resolution Imaging Spectroradiometer (MODIS) images taken during precipitation events reveal complex patterns of upstream open-cell convection over the ocean, stratus and/or convective clouds over the mountains, and sharp leeside clearing and roll convection over the steppe. Using the water vapor bands on MODIS reveals a sharp drop in column water vapor from about 1.4 to 0.7 cm across the mountain range.

Seventy-one water samples from streams across the southern Andes provide deuterium and oxygen-18 isotope data to determine the drying ratio (DR) of airstreams crossing the mountain range and to constrain free parameters in a mathematical model of orographic precipitation. From the strong isotope fractionation associated with orographic precipitation, it is estimated that DR is ∼50%, the highest value yet found for a mountain range. The cloud delay parameters in a high-resolution linear precipitation model were optimized to fit the streamwater isotope data. The model agrees well with the data when the cloud delay time (i.e., elapsed time from condensation to precipitation) is about 1700 s. The tuned model is used to discuss the small-scale spatial pattern of precipitation.

The isotope data from streams are also compared with data from sapwater. The good agreement suggests that future isotope mapping could be done using trees.
Some reflections on social workers’ perspectives on mental health services in two cities - Sydney, Australia and Budapest, Hungary
Authors: Weber Zita , Bugarszki Zsolt
Published: March 2007

English

This article reflects on the ways in which historical and political narratives have shaped social work practice in mental health in two cities, Sydney, Australia and Budapest, Hungary. A small sample of social workers was interviewed in the two cities and their perspectives highlighted many similarities in theoretical orientation to their practice.

French

Cette thèse s'arrête sur les façons dont les récits historiques et politiques ont façonnéla pratique du travail social dans deux villes, Sydney en Australie et Budapest en Hongrie. Un échantillon restreint de travailleurs sociaux ont étéinterviewés dans les deux villes et leurs perspectives ont mis en lumière un grand nombre de similitudes en ce qui a trait à l'orientation théorique de leur pratique.

Spanish

Se reflexiona sobre la manera en que narrativas históricas y políticas han dado forma a la práctica de trabajo social en Sydney (Australia) y Budapest (Hungría). Se entrevistóa una pequeña muestra de trabajadores sociales en las dos ciudades. Sus perspectivas muestran muchas semejanzas en la orientación teórica de su práctica.
Millennium Development Goals and Streamlining the UN Development Architectures
Authors: Fues Thomas
Published: March 2007

The Millennium Development Goals (MDGs) exemplify the enduring commitment and potential of the United Nations to serve as a catalyst for collective action in the cause of equitable and all round development of all nations and peoples. Indeed, the restructuring of the development apparatus as an important element of the larger challenge of the UN reform has acquired greater urgency in view of the manifest need to push for timely implementation of MDGs. Strengthening the role of the Economic and Social Council is a tricky issue that apparently puts the industrially advanced countries and the developing countries in opposite camps. Among the issues on which both the European developed and the Asian developing countries have showed interest, the idea of air ticket levy for raising resources for development is worthy of being pursued vigorously as part of the UN reform negotiations. Likewise, there is more than sufficient potential for old European Union countries like Germany and fast developing countries like China to bridge gaps in their policy objectives and work as partners in strengthening the multilateral mechanism dedicated to development purposes.
New Phase in UN Reforms
Authors: Murthy C.S.R.
Published: March 2007

The expectations about UN reforms in the wake of the end of the Cold War are dampened due to the strongly held divergent viewpoints among various groups of governments. In contrast to the euphoria generated by official and non-official panels churning out scores of ideas and proposals, the reforms actually carried out have remained cosmetic and minimal. The exception to this dismal trend is the establishment of the Peacebuilding Commission (PBC) and the Human Rights Council (HRC) in 2005 that provide the first exercise of reforms of an inter-governmental nature. There are several unique and innovative features associated with both these newly created bodies—their ambitious mandate, varied ways of composition, parallel structural supervision and so forth. The Asian and European regional groups have espoused often contrasting perspectives in negotiations on the creation of PBC and HRC, while the outcome of the bargaining showcases an interesting balance sheet of the gains and losses of principal organs of the UN, especially the General Assembly and the Security Council. Start-up and follow-up issues like sufficient funding of peacebuilding operations, efficacious coordination with an array of agencies and the independent and impartial scrutiny of human rights track record of countries are substantive and could stand between the success and failure of these innovations. Either way, the actual performance of these bodies may significantly influence the later stages of UN reforms.
Democratic Reform and Civil Society
Authors: Damron Danny
Published: March 2007

Theories of democratic consolidation often focus on the role a democratically committed civil society plays in deepening democracy without considering the reasons some groups in civil society are successful while others fail in that endeavor. To more precisely identify the contribution civic groups make, scholars should address both positive and negative outcomes of civic activism aimed at reform. While resource mobilization and political process theories note that success hinges on the differing abilities of civic groups to organize in ways that maximize their leverage over available resources and to mobilize potential participants in the movement, this study of civic groups in Korea shows that what matters most in determining success is not solely how civic groups are organized. The way civic groups convey their message seems to be the decisive factor determining whether their activism leads to democratic reform. This finding - that how civic groups frame their protest helps determine success - can help us more accurately differentiate democratically committed civic group contributions to democratic deepening. This will in turn help us better understand the direction and tempo of that deepening in third-wave democracies. The added emphasis on framing will also result in a more precise theoretical understanding of the relationship between democratic deepening and civil society.
Rescuing Thousands, Abandoning a Million: What Might an Emancipatory Intervention Have Looked Like in Rwanda?
Authors: Piiparinen Touko
Published: March 2007

The conceptual analysis of an ‘emancipatory intervention’, one that frees the people from repressive or genocidal political forces, has attracted scant attention in the debate on international relations. This has been partly due to the fact that the term has been hijacked by the pervasive liberal moral hubris which advocates greater missions1 under the guise of humanitarian intervention. This article aims to revive and reformulate the idea of emancipatory intervention by deriving lessons from Rwanda as an empirical case and by invoking humanitarian realism, which has the potential to move the vision of emancipatory intervention away from liberal interventionism. The ‘new yardstick’ of assessing emancipatory intervention is less ambitious, but more realistic: it is understood as the extent to which the intervening side might free itself from structural constraints in order to conduct a humanitarian intervention. In the Rwandan case, such possibilities specifically refer to structural cohesiveness, namely the capacity of the UN system to work efficiently when its powers are combined. They include not only the material powers of individual member states, as the mainstream literature has argued, but also rational-legal powers possessed by the UN Secretariat as well as control mechanisms. On this basis, the article constructs a vision of a ‘hammer and anvil’peacekeeping operation in Rwanda.
German Publizistikwissenschaft and its Shift from a Humanistic to an Empirical Social Scientific Discipline
Authors: Löblich Maria
Published: March 2007

German mass communication research today describes itself as an empirical social scientific discipline, but it has not always been so defined. For several decades Publizistikwissenschaft had considered itself as one of the humanities. But at the beginning of the 1960s, a scientific debate started about the discipline’s subjects, its methods and tasks. The forum for this debate was in the scholarly journal Publizistik. This article identifies the arguments and rhetorical repertoires employed by two scholars from opposite sides of the debate, Emil Dovifat and Elisabeth Noelle-Neumann, to convince the scientific community to side respectively with either the social science or the humanities camp. It is shown that an array of arguments were utilized, from the political meanings and ethical aspects of media, to epistemological reasoning. Furthermore, it is surprising to see how dramatic and emotional the rhetorical repertoires were. The article also presents the biographical, historical and political context of the development of Germany’s Publizistikwissenschaft.
The Extent and Organizational Determinants of Research Utilization in Canadian Health Services Organizations
Authors: Belkhodja Omar , Amara Nabil , Landry Réjean , Ouimet Mathieu
Published: February 2007

This article focuses on the use of research by managers and professionals in Canadian health service organizations (ministries, regional authorities, and hospitals). The results of the analysis of the 928 responses underlined the important role that the absorption, learning, culture, and linkage mechanism variables played in determining utilization. General linear regression and regression by organizational type confirmed the importance of the linkage mechanisms, research experience, unit size, and research relevance for the users. The emphasis could thus be put, according to the organization type, on research experience, linkage mechanisms, unit size, research culture, research relevance for the users, and research activities. The article also underscores the individual and organizational contextual factors’ high degree of significance by expressing these contextual factors as organizational variables and by adopting a more organizational perspective of knowledge utilization analysis.
Beyond the Autopoietic Principle? A Preliminary Analysis of the Freudian Cell
Authors: Nichols Joshua
Published: February 2007

This article begins with the question, is mind prefigured in life? Andreas Webber and Francisco Varela argue that the autopoietic model in combination with Jonas's theory of metabolism provide a more robust model than Kant's account of natural teleology in the third critique, and thus it is able to make a claim to, at least, a pre-figuration of human freedom. I argue that Freud's illustration of the death drive via the analogy of the cell in Beyond the Pleasure Principle provides a valuable counter-example to Jonas's conception of metabolism and exposes the type of metaphysical assumptions that the Kantian project was so averse to. My intention here is not to reify either Jonas or Freud's claims on the determinative nature of natural causation; rather it is to argue that each exists as valuable heuristic tools. Any causal determinative judgment on the nature of natural teleology must be exercised with nothing less than a Kantian level of caution as the implication of placing the value of the coherence of our conceptual structures over the actual mechanical processes of the natural world confronts us with the direct risk of misrecognition on a massive scale.
An introduction to causal modeling in clinical trials
Authors: Bellamy Scarlett L , Lin Julia Y , Have Thomas R Ten
Published: February 2007

Purpose We review and compare two causal modeling approaches that correspond to two major and distinct classes of inference – efficacy and interventionbased inference – in the context of randomized trials with subject noncompliance. Methods We review the definitions of efficacy and intervention-based effects in the clinical trials literature and relate these to two separate and distinct causal modeling approaches: the structural mean modeling (SMM) approach and the principal stratification, instrumental variable approach.

Results The SMM-based efficacy approach focuses on the effect of actually receiving treatment. In contrast, the principal stratification method addresses the effect of treatment assignment within partially unobserved latent subgroups defined by compliance behavior. While these approaches differ in terms of philosophy, model definitions, and estimation, they estimate the same causal effect under certain assumptions, but estimate very different causal effects when those assumptions are relaxed. We illustrate these results using a randomized psychiatry trial where the focus is physician compliance to the designated protocol and the other examines patient compliance to the designated protocol, both from the same trial.

Limitations The validity of the models under the instrumental variable, SMM and principal stratification approaches depends on modeling assumptions, some of which may not be verifiable from the observed data and potentially less realistic than the no-confounding assumption made by non-causal approaches.

Conclusions This comparison in terms of efficacy versus intervention-based effects in causal modeling parallels the explanatory versus pragmatic approaches in clinical trials research; therefore researchers should weigh carefully when choosing causal modeling methodology based on whether efficacy or intervention-based effects are of interest. Clinical Trials 2007; 4: 58–73; http://ctj.sagepub.com
Design and analysis issues in cardiac arrhythmia trials: insights from the Detect Supraventricular Tachycardia Trial
Authors: McClelland Robyn L , Bamlet William R , Glikson Michael , Friedman Paul A
Published: February 2007

Background The Detect Supraventricular Tachycardia (Detect SVT) trial was a randomized single blind study in subjects receiving a dual chamber implantable cardioverter defibrillator (ICD). The primary goal was to evaluate whether dual chamber enhancements result in greater discrimination between supraventricular tachycardia (SVT) and ventricular episodes when compared to ventricular-only enhancements.

Purpose The purpose of this report is to describe our experiences from an analytic perspective, including overall study design, the value of blinded episode review, and the statistical analysis plan.

Methods The Detect SVT study was a parallel group study, with blinded central review of all arrhythmia episodes occurring over a six-month period. The primary response was the proportion of inappropriate detections (SVT episodes that are inappropriately classified as ventricular by the device).

Results A parallel group design was essential as unplanned crossovers were very differential. The blinded review of episodes was a major use of resources, with over 2300 episodes observed. This review did not materially alter the findings, however, the avoidance of any perceived bias was a major strength. The value of collecting large numbers of episodes on a single subject was found to be minimal. A Kaplan–Meier analysis of the number of SVT episodes until first inappropriate detection was found to add additional information.

Limitations The recommendations reported here relate to cardiac arrhythmia trials, or other studies with very similar endpoints. These observations are based on the results of a single trial and should be confirmed in other studies.

Conclusions The parallel group design was essential, as was accounting for within-subject correlation in the analysis. The blinded review process was also important, but significant resources could be saved by closing-out episode collection after a fixed number of episodes. Lessons learned from the Detect SVT trial may prove useful to others designing trials in this active research area.
Communion, Unity and Primacy: An Anglican Response to Ut Unum Sint
Authors: Santer Mark
Published: February 2007

Pope John Paul II’s Encyclical Ut Unum Sint, published in 1995, was immediately recognized as a document of fundamental importance for ecumenism. John Paul II clearly and unequivocally renewed the Roman Catholic Church’s commitment to the ecumenical movement and invited leaders and theologians of other churches to engage with the Roman Catholic Church in patient and fraternal dialogue on the issue of the Petrine offices. A decade later this lecture reviews official Anglican responses to the Pope’s initiative and sets out issues which Anglicans need to address and explore.
The Praxis of Inculturation for Mission: Roberto de Nobili’s Example and Legacy
Authors: Collins Paul
Published: February 2007

This article investigates inculturation in the twentieth century in relation to the example and practice of the seventeenth-century Jesuit missionary Roberto de Nobili. Monastic and liturgical attempts at inculturation in South India are examined as well as the critique offered by Dalit Theology. There are four sections: (1) Outline and analysis of the practice of de Nobili, and its theological basis in the seventeenth century. (2) Analysis of the parallels between the praxis of de Nobili and various Christian sannyasi in the twentieth century, e.g. Savarirayan Jesudason, Ernest Forrester-Paton, Jack Winslow, Abhishiktananda, Bede Griffiths and Francis Acharya. (3) Evaluation of the practice, and its theological basis, of these sannyasi and other religious leaders in South India. (4) Investigation of the critique of Dalit Theology of these practices, and possible outcomes for future practice e.g. in relation to inter-religious dialogue.
Clinical Characteristics and Prognostic Factors of Postencephalitic Epilepsy in Children
Authors: Chen Yung-Jung , Fang Peng-Cheng , Chow Julie Chiu
Published: February 2007

The goal of this study was to clarify the clinical characteristics and prognostic factors of childhood postencephalitic epilepsy. Forty-four patients (20 boys and 24 girls; age range 21 months to 17 years, mean age 8.1 ± 4.6 years) with postencephalitic epilepsy were selected from the 798 epileptic children treated and followed up at our hospital between 1993 and 2003. The clinical data included clinical features, electroencephalograms (EEGs), and neuroimages, all reviewed and analyzed retrospectively. Based on their post-treatment seizure outcomes, the children were divided into favorable (n = 20) and poor outcome groups (n = 24). Between the two groups, the age at encephalitis, cerebrospinal fluid findings, and seizure type were comparable. Factors indicating a poor prognosis for these patients during the acute phase of encephalitis were (1) status epilepticus occurring as the first seizure (P < .005), (2) slow background activity (P < .001) and multifocal spike discharges on EEGs (P < .01), and (3) herpes simplex viral encephalitis (P < .01). Our findings indicated that patients with status epilepticus and multifocal spikes on EEG during acute encephalitis have an increased risk of developing intractable epilepsy. To improve the outcome of postencephalitic epilepsy, intervention must occur earlier in the encephalitis stage.
Mild hypothermia reduces cardiac post-ischemic reactive hyperemia
Authors: Olivecrona Goran K , Götberg Matthias , Harnek Jan , Van der Pals Jesper , Erlinge David
Published: February 2007

Background

In experimentally induced myocardial infarction, mild hypothermia (33–35°C) is beneficial if applied prior to ischemia or reperfusion. Hypothermia, when applied after reperfusion seems to confer little or no benefit. The mechanism by which hypothermia exerts its cell-protective effect during cardiac ischemia remains unclear. It has been hypothesized that hypothermia reduces the reperfusion damage; the additional damage incurred upon the myocardium during reperfusion. Reperfusion results in a massive increase in blood flow, reactive hyperemia, which may contribute to reperfusion damage. We postulated that hypothermia could attenuate the post-ischemic reactive hyperemia.

Methods

Sixteen 25–30 kg pigs, in a closed chest model, were anesthetized and temperature was established in all pigs at 37°C using an intravascular cooling catheter. The 16 pigs were then randomized to hypothermia (34°C) or control (37°C). The left main coronary artery was then catheterized with a PCI guiding catheter. A Doppler flow wire was placed in the mid part of the LAD and a PCI balloon was then positioned proximal to the Doppler wire but distal to the first diagonal branch. The LAD was then occluded for ten minutes in all pigs. Coronary blood flow was measured before, during and after ischemia/reperfusion.

Results

The peak flow seen during post-ischemic reactive hyperemia (during the first minutes of reperfusion) was significantly reduced by 43 % (p < 0.01) in hypothermic pigs compared to controls.

Conclusion

Mild hypothermia significantly reduces post-ischemic hyperemia in a closed chest pig model. The reduction of reactive hyperemia during reperfusion may have an impact on cardiac reperfusion injury.
Evaluation of procalcitonin for diagnosis of neonatal sepsis of vertical transmission
Authors: López Sastre José B , Pérez Solís David , Roqués Serradilla Vicente , Fernández Colomer Belén , Coto Cotallo Gil D ,   Grupo de Hospitales Castrillo
Published: February 2007

Background

The results of recent studies suggest the usefulness of PCT for early diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to determine the behavior of serum PCT concentrations in both uninfected and infected neonates, and to assess the value of this marker for diagnosis of neonatal sepsis of vertical transmission.

Methods

PCT was measured in 827 blood samples collected prospectively from 317 neonates admitted to 13 acute-care teaching hospitals in Spain over one year. Serum PCT concentrations were determined by a specific immunoluminometric assay. The diagnostic efficacy of PCT at birth and within 12–24 h and 36–48 h of life was evaluated calculating the sensitivity, specificity, and likelihood ratio of positive and negative results.

Results

169 asymptomatic newborns and 148 symptomatic newborns (confirmed vertical sepsis: 31, vertical clinical sepsis: 38, non-infectious diseases: 79) were studied. In asymptomatic neonates, PCT values at 12–24 h were significantly higher than at birth and at 36–48 h of life. Resuscitation at birth and chorioamnionitis were independently associated to PCT values. Neonates with confirmed vertical sepsis showed significantly higher PCT values than those with clinical sepsis. PCT thresholds for the diagnosis of sepsis were 0.55 ng/mL at birth (sensitivity 75.4%, specificity 72.3%); 4.7 ng/mL within 12–24 h of life (sensitivity 73.8%, specificity 80.8%); and 1.7 ng/mL within 36–48 h of life (sensitivity 77.6%, specificity 79.2%).

Conclusion

Serum PCT was moderately useful for the detection of sepsis of vertical transmission, and its reliability as a maker of bacterial infection requires specific cutoff values for each evaluation point over the first 48 h of life.
Cost-effectiveness of collaborative care for chronically ill patients with comorbid depressive disorder in the general hospital setting, a randomised controlled trial
Authors: Horn Eva K , van Benthem Tjeerd B , Hakkaart-van Roijen Leona , van Marwijk Harm WJ , Beekman Aartjan TF , Rutten Frans F , van der Feltz-Cornelis Christina M
Published: February 2007

Background

Depressive disorder is one of the most common disorders, and is highly prevalent in chronically ill patients. The presence of comorbid depression has a negative influence on quality of life, health care costs, self-care, morbidity, and mortality. Early diagnosis and well-organized treatment of depression has a positive influence on these aspects. Earlier research in the USA has reported good results with regard to the treatment of depression with a collaborative care approach and an antidepressant algorithm. In the UK 'Problem Solving Treatment' has proved to be feasible. However, in the general hospital setting this approach has not yet been evaluated.

Methods/Design

CC: DIM (Collaborative Care: Depression Initiative in the Medical setting) is a two-armed randomised controlled trial with randomisation at patient level. The aim of the trial is to evaluate the treatment of depressive disorder in general hospitals in the Netherlands based on a collaborative care framework, including contracting, 'Problem Solving Treatment', antidepressant algorithm, and manual-guided self-help. 126 outpatients with diabetes mellitus, chronic obstructive pulmonary disease, or cardiovascular diseases will be randomised to either the intervention group or the control group. Patients will be included if they have been diagnosed with moderate to severe depression, based on the DSM-IV criteria in a two-step screening method. The intervention group will receive treatment based on the collaborative care approach; the control group will receive 'care as usual'. Baseline and follow-up measurements (after 3, 6, 9, and 12 months) will be performed by means of questionnaires. The primary outcome measure is severity of depressive symptoms, as measured with the PHQ-9. The secondary outcome measure is the cost-effectiveness of these treatments according to the TiC-P, the EuroQol and the SF-36.

Discussion

Earlier research has indicated that depressive disorder is a chronic, mostly recurrent illness, which tends to cluster with physical comorbidity. Even though the treatment of depressive disorder based on the guidelines for depression is proven effective, these guidelines are often insufficiently adhered to. Collaborative care and 'Problem Solving Treatment' will be specifically tailored to patients with depressive disorders and evaluated in a general hospital setting in the Netherlands.
The acceptability of waiting times for elective general surgery and the appropriateness of prioritising patients
Authors: Oudhoff Jurriaan P , Timmermans Danielle RM , Rietberg Martin , Knol Dirk L , van der Wal Gerrit
Published: March 2007

Background

Problematic waiting lists in public health care threaten the equity and timeliness of care provision in several countries. This study assesses different stakeholders' views on the acceptability of waiting lists in health care, their preferences for priority care of patients, and their judgements on acceptable waiting times for surgical patients.

Methods

A questionnaire survey was conducted among 257 former patients (82 with varicose veins, 86 with inguinal hernia, and 89 with gallstones), 101 surgeons, 95 occupational physicians, and 65 GPs. Judgements on acceptable waiting times were assessed using vignettes of patients with varicose veins, inguinal hernia, and gallstones.

Results

Participants endorsed the prioritisation of patients based on clinical need, but not on ability to benefit. The groups had significantly different opinions (p < 0.05) on the use of non-clinical priority criteria and on the need for uniformity in the prioritisation process.

Acceptable waiting times ranged between 2 and 25 weeks depending on the type of disorder (p < 0.001) and the severity of physical and psychosocial problems of patients (p < 0.001). Judgements were similar between the survey groups (p = 0.3) but responses varied considerably within each group depending on the individual's attitude towards waiting lists in health care (p < 0.001).

Conclusion

The explicit prioritisation of patients seems an accepted means for reducing the overall burden from waiting lists. The disagreement about appropriate prioritisation criteria and the need for uniformity, however, raises concern about equity when implementing prioritisation in daily practice.

Single factor waiting time thresholds seem insufficient for securing timely care provision in the presence of long waiting lists as they do not account for the different consequences of waiting between patients.