bluuebunny/crossref_metadata_2025 huggingface dataset:
Soluble Guanylate Cyclase Activator Reverses Acute Pulmonary Hypertension and Augments the Pulmonary Vasodilator Response to Inhaled Nitric Oxide in Awake Lambs
Authors: Evgenov Oleg V. , Ichinose Fumito , Evgenov Natalia V. , Gnoth Mark J. , Falkowski George E. , Chang Yuchiao , Bloch Kenneth D. , Zapol Warren M.
Published: October 2004

Background—

Inhaled nitric oxide (NO) is a potent and selective pulmonary vasodilator, which induces cGMP synthesis by activating soluble guanylate cyclase (sGC) in ventilated lung regions. Carbon monoxide (CO) has also been proposed to influence smooth muscle tone via activation of sGC. We examined whether direct stimulation of sGC by BAY 41-2272 would produce pulmonary vasodilation and augment the pulmonary responses to inhaled NO or CO.

Methods and Results—

In awake, instrumented lambs, the thromboxane analogue U-46619 was intravenously administered to increase mean pulmonary arterial pressure to 35 mm Hg. Intravenous infusion of BAY 41-2272 (0.03, 0.1, and 0.3 mg · kg
−1
· h
−1
) reduced mean pulmonary arterial pressure and pulmonary vascular resistance and increased transpulmonary cGMP release in a dose-dependent manner. Larger doses of BAY 41-2272 also produced systemic vasodilation and elevated the cardiac index.
N
ω
-nitro-
l
-arginine methyl ester abolished the systemic but not the pulmonary vasodilator effects of BAY 41-2272. Furthermore, infusing BAY 41-2272 at 0.1 mg · kg
−1
· h
−1
potentiated and prolonged the pulmonary vasodilation induced by inhaled NO (2, 10, and 20 ppm). In contrast, inhaled CO (50, 250, and 500 ppm) had no effect on U-46619–induced pulmonary vasoconstriction before or during administration of BAY 41-2272.

Conclusions—

In lambs with acute pulmonary hypertension, BAY 41-2272 is a potent pulmonary vasodilator that augments and prolongs the pulmonary vasodilator response to inhaled NO. Direct pharmacological stimulation of sGC, either alone or in combination with inhaled NO, may provide a novel approach for the treatment of pulmonary hypertension.
Spectrum and Frequency of Cardiac Channel Defects in Swimming-Triggered Arrhythmia Syndromes
Authors: Choi Grace , Kopplin Laura J. , Tester David J. , Will Melissa L. , Haglund Carla M. , Ackerman Michael J.
Published: October 2004

Background—

Swimming is a relatively genotype-specific arrhythmogenic trigger for type 1 long-QT syndrome (LQT1). We hypothesize that mimickers of concealed LQT1, namely catecholaminergic polymorphic ventricular tachycardia (CPVT), may also underlie swimming-triggered cardiac events.

Methods and Results—

Between August 1997 and May 2003, 388 consecutive, unrelated patients were referred specifically for LQTS genetic testing. The presence of a personal and/or family history of a near-drowning or drowning was determined by review of the medical records and/or phone interviews and was blinded to genetic test results. Comprehensive mutational analysis of the 5 LQTS-causing channel genes,
KCNQ1
(LQT1),
KCNH2
(LQT2),
SCN5A
(LQT3),
KCNE1
(LQT5), and
KCNE2
(LQT6), along with
KCNJ2
(Andersen-Tawil syndrome) and targeted analysis of 18 CPVT1-associated exons in
RyR2
, was performed with the use of denaturing high-performance liquid chromatography and direct DNA sequencing. Approximately 11% (43 of 388) of the index cases had a positive swimming phenotype. Thirty-three of these 43 index cases had a “Schwartz” score (≥4) suggesting high clinical probability of LQTS. Among this subset, 28 patients (85%) were LQT1, 2 patients (6%) were LQT2, and 3 were genotype negative. Among the 10 cases with low clinical probability for LQTS, 9 had novel, putative CPVT1-causing
RyR2
mutations.

Conclusions—

In contrast to previous studies that suggested universal LQT1 specificity, genetic heterogeneity underlies channelopathies that are suspected chiefly because of a near-drowning or drowning. CPVT1 and strategic genotyping of
RyR2
should be considered when LQT1 is excluded in the pathogenesis of a swimming-triggered arrhythmia syndrome.
Effect of Candesartan on Cause-Specific Mortality in Heart Failure Patients
Authors: Solomon Scott D. , Wang Duolao , Finn Peter , Skali Hicham , Zornoff Leonardo , McMurray John J.V. , Swedberg Karl , Yusuf Salim , Granger Christopher B. , Michelson Eric L. , Pocock Stuart , Pfeffer Marc A.
Published: October 2004

Background—

Patients with heart failure are at increased risk of sudden death and death attributed to progressive pump failure. We assessed the effect of candesartan on cause-specific mortality in patients enrolled in the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) program.

Methods and Results—

The CHARM program consisted of 3 component trials that enrolled patients with symptomatic heart failure: CHARM-Alternative (n=2028; LVEF⩽40% and ACE intolerant), CHARM-Added (n=2548; LVEF⩽40%, already on ACE inhibitors), and CHARM-Preserved (n=3023; LVEF >40%). Patients were randomized to candesartan, titrated to 32 mg QD, or placebo and were followed up for a median of 37.7 months. All deaths were reviewed by a blinded adjudication committee and categorized according to prespecified definitions on the basis of a narrative and source documentation. The number and rate of deaths by cause were calculated for each of the component trials and the overall program. Of all the patients, 8.5% died suddenly, and 6.2% died of progressive heart failure. Candesartan reduced both sudden death (HR 0.85 [0.73 to 0.99],
P
=0.036) and death from worsening heart failure (HR 0.78 [0.65 to 0.94],
P
=0.008). These reductions were most apparent in the patients with LVEF⩽40%.

Conclusions—

Candesartan reduced sudden death and death from worsening heart failure in patients with symptomatic heart failure, although this reduction was most apparent in patients with systolic dysfunction.
Mechanisms for Increased Glycolysis in the Hypertrophied Rat Heart
Authors: Nascimben Luigino , Ingwall Joanne S. , Lorell Beverly H. , Pinz Ilka , Schultz Vera , Tornheim Keith , Tian Rong
Published: October 2004

Glycolysis increases in hypertrophied hearts but the mechanisms are unknown. We studied the regulation of glycolysis in hearts with pressure-overload LV hypertrophy (LVH), a model that showed marked increases in the rates of glycolysis (by 2-fold) and insulin-independent glucose uptake (by 3-fold). Although the V
max
of the key glycolytic enzymes was unchanged in this model, concentrations of free ADP, free AMP, inorganic phosphate (P
i
), and fructose-2,6-bisphosphate (F-2,6-P
2
), all activators of the rate-limiting enzyme phosphofructokinase (PFK), were increased (up to 10-fold). Concentrations of the inhibitors of PFK, ATP, citrate, and H
+
were unaltered in LVH. Thus, our findings show that increased glucose entry and activation of the rate-limiting enzyme PFK both contribute to increased flux through the glycolytic pathway in hypertrophied hearts. Moreover, our results also suggest that these changes can be explained by increased intracellular free [ADP] and [AMP], due to decreased energy reserve in LVH, activating the AMP-activated protein kinase cascade. This, in turn, results in enhanced synthesis of F-2,6-P
2
and increased sarcolemma localization of glucose transporters, leading to coordinated increases in glucose transport and activation of PFK.
Mechanisms for Aldosterone and Spironolactone-Induced Positive Inotropic Actions in the Rat Heart
Authors: Barbato John C. , Rashid Sumia , Mulrow Patrick J. , Shapiro Joseph I. , Franco-Saenz Roberto
Published: October 2004

Previously, we reported that aldosterone and spironolactone have inotropic effects in the isolated perfused heart. To address the mechanisms underlying these inotropic effects, we examined the effects of aldosterone and spironolactone on isolated cardiac myocyte shortening, intracellular calcium ([Ca
+2
]
i
), pHi, and calcium-dependent actinomyosin ATPase activity. Aldosterone significantly increased shortening in cardiac myocytes (8.0±1.0 versus 16.0±1.3%,
P
<0.01) but neither diastolic [Ca
+2
]
i
(61.0±1.1 versus 66.0±4.4 nmol/L) nor peak systolic [Ca
+2
]
i
(302±11 versus 304±17 nmol/L) was affected. Spironolactone-increased shortening was also not coupled with changes in peak systolic calcium; however, diastolic calcium was significantly increased by spironolactone. Aldosterone, but not spironolactone, increased pHi from 7.23±0.03 to 7.59±0.02 (
P
<0.01); this was completely blocked by coadministration of 100 μmol/L of ethyl-isopropyl amiloride (EIPA), an inhibitor of the Na
+
/H
+
exchanger (
P
<0.01). Consistent with this finding, aldosterone increased cytosolic sodium concentration ([Na
+
]
i
) from 9.2±0.15 to 11.4±0.2 mmol/L and produced a leftward shift in the pCa ATPase curve (pCa=5.82±0.02 versus 6.35±0.02,
P
<0.01) without affecting maximal myosin ATPase activity. Conversely, spironolactone, but not aldosterone, significantly increases maximal actomyosin ATPase activity (837±59 versus 355±52 nmol inorganic phosphate (P
i
) · min
−1
· g tissue
−1
). Collectively, these data strongly suggest that the inotropic actions of aldosterone and spironolactone are caused by different mechanisms of action. Aldosterone appeared to increase inotropy primarily through increased cytosolic pH, whereas spironolactone increased myosin ATPase calcium sensitivity and diastolic calcium concentration.
Critical Role for the α-1B Adrenergic Receptor at the Sympathetic Neuroeffector Junction
Authors: Townsend Seth A. , Jung Albert S. , Hoe Yen Shi Gillian , Lefkowitz Rafael Y. , Khan Shakil A. , Lemmon Christoper A. , Harrison Robert W. , Lee KwanghHo , Barouch Lili A. , Cotecchia Susanna , Shoukas Artin A. , Nyhan Daniel , Hare Joshua M. , Berkowitz Dan E.
Published: October 2004

The α-1 adrenergic receptors (α
1
ARs) are critical in sympathetically mediated vasoconstriction. The specific role of each α
1
AR subtype in regulating vasoconstriction remains highly controversial. Limited pharmacological studies suggest that differential α
1
AR responses may be the result of differential activation of junctional versus extrajunctional receptors. We tested the hypothesis that the α
1B
AR subtype is critical in mediating sympathetic junctional neurotransmission. We measured in vivo integrated cardiovascular responses to a hypotensive stimulus (induced via transient bilateral carotid occlusion [TBCO]) in α
1B
AR knockout (KO) mice and their wild-type (WT) littermates. In WT mice, after dissection of the carotid arteries and denervation of aortic baroreceptor buffering nerves, TBCO produced significant pressor and positive inotropic effects. Both responses were markedly attenuated in α
1B
AR KO mice (change systolic blood pressure 46±8 versus 11±2 mm Hg; percentage change in the end-systolic pressure-volume relationship [ESPVR] 36±7% versus 12±2%; WT versus KO;
P
<0.003). In vitro α
1
AR mesenteric microvascular contractile responses to endogenous norepinephrine (NE; elicited by electrical field stimulation 10 Hz) was markedly depressed in α
1B
AR KO mice compared with WT (12.4±1.7% versus 21.5±1.2%;
P
<0.001). In contrast, responses to exogenous NE were similar in α
1B
AR KO and WT mice (22.4±7.3% versus 33.4±4.3%; NS). Collectively, these results demonstrate a critical role for the α
1B
AR in baroreceptor-mediated adrenergic signaling at the vascular neuroeffector junction. Moreover, α
1B
ARs modulate inotropic responses to baroreceptor activation. The critical role for α
1B
AR in neuroeffector regulation of vascular tone and myocardial contractility has profound clinical implications for designing therapies for orthostatic intolerance.
Models of Health Care Rationing
Authors: Schmidt Volker H.
Published: October 2004

The article discusses and exemplifies three models of health care rationing observed in affluent, economically advanced countries. Its underlying premise is that no welfare system in the world can be exempted from any rationing whatsoever. This raises the question as to how the problem ought best to be resolved. But before thinking about normatively appealing answers it might be helpful to study how the problem is actually dealt with in the real world. For such a study brings to light several advantages and drawbacks of various rationing schemes which it would be hard to consider (even conceive) in the abstract alone, but whose knowledge may be highly relevant, perhaps indispensable, for the designation of adequate solutions.
Status Inconsistency as Predictor of Public Action Attitudes in Romania
Authors: Sandu Dumitru
Published: October 2004

The article addresses the problem of status inconsistency as a predictor of public action attitudes. Its first basic hypothesis is that democratic, authoritarian, participatory and rebellion attitudes towards the way in which public problems are solved can be identified as relevant social types in a transition society. Specific social segments are structured around these attitudes. The second hypothesis implies that status inconsistencies, at household or personal levels, have a significant predictive power in explaining the structuring of these attitudes, even when the vertical dimensions of status, context and cognitive factors are controlled. The four attitude groups could be located within Almond and Verba’s taxonomy of political culture. Authoritarians are bearers of subject culture. Rebellion-oriented people are closer to parochial or parochial-subject culture. Democratic orientation points to subject-participatory political culture. The participatory orientation is relevant for participatory culture or, in some of its weak forms, parochial-participatory values.
Explaining knowledge sharing in organizations through the dimensions of social capital
Authors: Widén-Wulff Gunilla , Ginman Mariam
Published: October 2004

The increasing complexity of organizations, together with the growing scale of information activities, puts new demands on business corporations. It is believed that investing in social values based on mutuality, trust and respect could yield long-term benefits such as corporate well-being and innovativeness. The benefits are believed to be based on better knowledge sharing, lower transaction costs due to a communicative spirit, and a greater coherence of action. However, the concept of social capital in the field of information behaviour in organizations is new and needs a more solid theoretical framework. The objective of this paper is to contribute to a better understanding of how social and informative aspects are anchored to each other and to explore the mechanisms behind knowledge sharing. Possible measures and contexts for this kind of research are suggested.
On requesting conference papers electronically
Authors: Hartley James
Published: October 2004

Aims. The aims of this study were (i) to determine the success rate for obtaining conference papers by using e-mail, and (ii) to compare the results with those found previously for reprints of published papers.

Method. 100 requests for copies of papers delivered at a conference in the USA were made by e-mail from the UK. A reminder was sent to the appropriate authors if no paper had been received within three weeks.

Results. 54 papers were received within six weeks. Most came by return or within one day, and all came electronically. Few of these papers could be described as conference papers, however, as the majority of them were copies of papers prepared for publication elsewhere. In addition, many lacked the information necessary for them to be adequately cited in other publications.
Rearranging the deckchairs on the Titanic of long-term care - is organizational integration the answer?
Authors: Glendinning Caroline , Means Robin
Published: October 2004

Since 1997 the British government has actively promoted collaboration between health and social care services, culminating in proposals for fully integrated health and social care organizations -called Care Trusts - to address problems in co-ordinating services for older people. This paper draws on historical evidence to examine the origins and development of these difficulties. A consistent theme over the past 50 years has been the changing role of health services in the provision of long-term support for older people and the consequent redefinition of the boundaries between health and social services. However, these changes have largely not been matched by corresponding transfers of resources that might enable social services to meet their increased responsibilities. Moreover, the demands of the acute hospital sector risk marginalizing the social support valued by older people themselves. The paper argues that organizational restructuring will therefore fail to improve coordination between health and social services for older people unless these underlying issues are also addressed.
‘A land of milk and honey’? Social policy in Scotland after Devolution
Authors: Mooney Gerry , Poole Lynne
Published: October 2004

This paper questions the extent to which a distinctively Scottish social welfare policy has emerged post-Devolution. Exploring the myths that continue to pervade the discussion and analysis of Scottish society today, it is argued that the scope for policy departure is limited in a number of different ways. While acknowledging that there are important institutional and implementation differences that can and do affect the delivery of welfare in Scotland and England, nonetheless the paper argues that there is a need to acknowledge the similarities between New Labour policy in London and in Edinburgh, to go beyond narrow institutional-centred approaches and to explore both the social relations that underpin and shape the delivery of social policy and the mounting contradictions that are at the heart of the New Labour project.
Equal shares: rights for fathers or recognition for children?
Authors: Smart Carol
Published: October 2004

The fathers’ rights movement in England has recently been given a huge boost by the involvement of Bob Geldof who has become their influential mouthpiece in the media and elsewhere. The movement has also diversified and adopted more high profile tactics more akin to those used in Australia and New Zealand. These tactics have challenged family law to adopt a principle of pure equality between mothers and fathers and demands that, on divorce or separation, children should be shared equally. In this paper it is argued that this demand ignores entirely the experiences of children who have lived an ‘equal shares’ arrangement for many years and that it reduces children to passive objects who can have no voice in a system designed only to create equality between adults. It is argued that rather than pushing the principles of family law back towards simplistic notions of equality, what is needed is a policy based on recognition rather than rights.
Imagining the Asian gang: ethnicity, masculinity and youth after ‘the riots’
Authors: Alexander Claire
Published: October 2004

The paper explores the discourses surrounding the ‘riots’ of 2001 as a reflection of contemporary understandings of raced/ethnic, gendered and generational identities, and changing discourses about race and ethnicity in Britain. The paper examines these themes in relation to current academic theorizations of culture, identity and difference. Finally, the paper explores the implementation of these understandings in current government policy papers and practices around ‘community cohesion’ and ‘citizenship’. It argues that each of these arenas employs very static and bounded notions of ‘community’, ‘culture’ and ‘identity’ which deny the complex formations of lived identities and obscures ongoing relations of power and disadvantage. This has clear implications for the future of multicultural policy, citizenship education and social justice.
Mapping citizen expertise about environmental risk of breast cancer
Authors: Potts Laura
Published: October 2004

A range of different communities of interest make knowledge claims regarding the association between environmental hazards and breast cancer, including policy makers, epidemiologists, scientists, activists in the breast cancer/environment movement, and women with breast cancer. The paper considers how the fences and defences between these groupings are maintained through differential relations of power and legitimacy, and how these are challenged by the ‘citizen expertise’ of those in the movement. This has the potential to yield a repositioning of science in society, based on an eco-social epidemiological paradigm and the paramountcy of public health protection. The paper draws on the author’s involvement in the breast cancer/environment movement in the UK and, to a more limited extent, in the Bay Area of California; it also suggests some initial insights from a small-scale pilot study undertaken as part of the Economic and Social Research Council’s Science in Society programme. In particular, it considers how the expertise of citizens, captured through a process of community mapping, may usefully contribute to an understanding of breast cancer aetiology that includes experiential, embodied knowledge.
The Cocoon—A Traveling Space
Authors: Dobers Peter , Strannegård Lars
Published: October 2004

As a graduation project at a design school in Stockholm, a piece of furniture to be used for retreats in the public space was exhibited. It was named ‘The Cocoon’ and was a reclining chair covered with a bubble-like construction made out of cloth and steel. The exhibition was a starting point for a number of journeys. In the years to come, the Cocoon reached museums, exhibition halls, newspapers and magazines throughout the world. In this article, we track the travels and illustrate the transformations of the Cocoon. We seek to understand spacing activities behind the travels and view the travels from a spatial perspective focusing on the relation between transportation and transformation, of emptiness, form and content.
Spatio-temporal Notions and Organized Environmental Issues: An Axiology of Action
Authors: Rämö Hans
Published: October 2004

The aim of this paper is to bring together temporal and spatial notions into a different set of axiologic pairs, and to trace examples in which such a set of pairs might be illuminating in accounts of how environmental issues are perceived in various social science disciplines. The paper begins with a division of time into reified clock time (chronos) and timely kairos time, together with a spatial division between abstract space (chora) and concrete place (topos). To better comprehend these originally Greek spatial and temporal notions, some Aristotelian concepts of human action will also be used (i.e. theoria/episteme, poiesis/techne and praxis/phronesis). These extended notions of human action, time and space/place are discussed in conjunction with aesthetics, ethics and environmental issues in the different organizational settings of science, mass media, business management and environmentalism.
Ideology, Science and Social Relations
Authors: Smith Dorothy E.
Published: October 2004

The article argues that Marx’s use of the concept of ideology in The German Ideology is incidental to a sustained critique of how those he described as the German ideologists think and reason about society and history and that this critique is not simply of an idealist theory that represents society and history as determined by consciousness but of methods of reasoning that treat concepts, even of those of political economy, as determinants. His view of how consciousness is determined historically by our social being does not envisage some kind of mechanical transfer of class status to class consciousness. Rather, he works with an epistemology that takes the concepts foundational to political economy as expressions or reflections of the social relations of a mode of production. The difference between ideology and science is the difference between treating those concepts as the primitives of theory and treating them as sites for exploring the social relations that are expressed in them. Thus, the historical rather than further undermining claims to knowledge, provides both the conditions under which knowledge is possible and its limitations.
Civil Society’s Barbarisms
Authors: Heins Volker
Published: October 2004

Instead of arguing about elements and boundaries of civil society, recent discussions in social theory have focused on the concept of civil society itself as embedded in different currents of social and political thought. Following up on these discussions, this article reconstructs the concept of civil society by identifying a number of implicit oppositional terms and the respective semantic fields, which in different historical contexts have lent meaning to the concept. Three such oppositional terms and counter-meanings will be distinguished in turn and traced back to different traditions of European social and political theory: (1) the barbarism of disorder; (2) the barbarism of order; and (3) the realm of toil and material necessity. It is argued that the multiple meanings and counter-meanings of civil society are connected by a deep structure of discourse. This deep structure of civil society thinking can be translated into a ‘semiotic square’ in the tradition of A.J. Greimas. In conclusion, it is suggested to further investigate current uses of civil society along these lines, in order to clarify normative goals and possible ways of mediating between opposing moral worlds.
Coalinga Chrysotile - The Case of the Missing “Asbestos Study”: Corporate Connivance or Plaintiff Ploy?
Authors: Ilgren E. B.
Published: October 2004

Significant results from one of the largest asbestos inhalation studies ever done were never published. Over the last 10 years, some of these have been found and reported in a series of papers in this journal. The “missing” data from the study were largely concerned with the potential chronic effects of short fibre chrysotile but also dealt with the alleged ability of a single, high dose exposure to long fibre chrysotile to produce a risk of disease for life (so-called “irreversibility”). Given its ubiquity and the notion held by the US Government and Plaintiff that all forms of asbestos are equally potent in even the smallest doses, the where-withal to scientifically “exonerate” short fibre chrysotile as a human health hazard would have very major regulatory, socio-economic and legal implications. The US Government was aware that the issues of fibre length and irreversibility had to be scientifically resolved and so funded the study. California Coalinga chrysotile was used as the “standard” short fibre material for the chronic inhalation assay: initially a 12-month exposure to fibre and then lifetime follow up. The “irreversibility” question was tested with a long fibre chrysotile from the Canadian Jeffrey mine: an initial high dose 1-hour to 1-day exposure and then 2-year follow-up. This report summarises how some of these missing data were found and discusses their relevance.
Coalinga Chrysotile: A Short-Fibre, Amphibole-Free, Chrysotile: Part VI - Additional Evidence for Lack of Fibrogenicity
Authors: Ilgren E. B.
Published: October 2004

This report describes additional unpublished data that support the notion that Coalinga chrysotile is not fibrogenic. These data are from the same long-term, NTP-NIEHS, chronic chrysotile inhalation study that served as the basis for our earlier publications which concluded that Coalinga chrysotile was not fibrogenic due to its lack of biopersistence. Wagner-scored 12 and 24 month interim sacrifice data from the NTP-NIEHS investigation and an unpublished data set from the comparison MRC study both previously unreported, were recently found in the author’s files. The histology slides and attendant data should have been amongst the materials archived at the NTP but were not present at the time the author reviewed those files in 1995 and 1996. Review of these new materials showed that Coalinga chrysotile did not produce fibrosis either at 12 or 24 months in contrast to the two Canadian preparations which were both fibrogenic even at this early stage of the study. These new data and related testimony greatly strengthen our earlier conclusions and serve to refute earlier apparently contradictory reports. International and Governmental Reports support the conclusion reached in our papers that Coalinga chrysotile is not pathogenic. In fact, the only scientists to criticise our conclusions have been in litigation against Union Carbide.
Collaborating within the ‘risk zone’
Authors: Nomdo Gideon J.
Published: October 2004

Universities have realized the need to equip students with appropriate information and computer technology (ICT) skills to prepare them for the workplace. This paper highlights a situation in which academics are uncomfortable with the new technological innovations being used to enhance teaching and learning. The need to integrate technology into teaching practices is an unavoidable reality. Used here is the lens of experiential learning to engage in a self-reflective case study of collaboration with the Multimedia Education Group at the University of Cape Town. The factors necessary for successful collaboration are underlined and emphasis is placed on the need for academics to reflect critically on their practice. It is argued that critical engagement with ICT provides academics with the opportunity to lead by example in the quest to enhance student learning.
The usefulness of structured mid-term feedback as a catalyst for change in higher education classes
Authors: Diamond Miriam Rosalyn
Published: October 2004

Structured mid-term feedback allows teaching staff to evaluate their effectiveness from the student perspective while the term is in session. Why do lecturers participate in these programs? What do they feel they learn as a result? How do they use the information gathered? Do these programs promote change in the way classes are conducted? At one university, a study was conducted to find out. Over two years, 82 Small Group Instructional Diagnoses (SGIDs) were conducted for staff in a range of disciplines. End-of-term surveys of participating lecturers revealed that this procedure increased their understanding of how students respond to their instructional methods. As a result, lecturers refined grading procedures, implemented new approaches to conducting classes, clarified their expectations of students, and refocused content emphasis. They also indicated that they intended to amend the way they teach future courses in an effort to increase effectiveness.
The contribution of work-based supervision to interprofessional learning on a masters programme in Community Mental Health
Authors: Bailey Di
Published: October 2004

This paper explores the contribution of work-based supervision to an education programme in mental health from the perspectives of supervisors and supervisees. It attempts to clarify the supervisory role by looking at the literature together with supervisors’ reported learning and development needs. Supervisors responded positively to a development programme established to help them support their learners. Quantitative data revealed differences between professional groups in respect of their exposure to interprofessional supervision, and individual rather than group supervision is more likely to be delivered in the workplace, which may limit opportunities for interprofessional learning transfer. Feedback from supervisors and supervisees shows consensus that supervision sessions focusing on academic work are rated of highest priority. This poses a challenge for programme providers to develop assignment methods that require workers to be change agents in their practice whilst also demonstrating academic standards.
High stakes testing, educational aims and ideals, and responsible assessment
Authors: Siegel Harvey
Published: October 2004

School and government officials, system administrators and other policymakers offer a variety of reasons for engaging in high stakes testing: to monitor student performance, to measure teacher and/or school effectiveness, to ensure accountability, etc. Some of these reasons are good; others not. But the best reason - one that is never offered, because it is not true - is that such testing furthers our efforts to realize our considered educational aims and ideals. I argue that while some testing is perfectly legitimate, current high stakes testing practice is largely inimical to the achievement of our most defensible educational ends.
Educational measurement and knowledge of other minds
Authors: Curren Randall R.
Published: October 2004

This article addresses the capacity of high stakes tests to measure the most significant kinds of learning. It begins by examining a set of philosophical arguments pertaining to construct validity and alleged conceptual obstacles to attributing specific knowledge and skills to learners. The arguments invoke philosophical doctrines of holism and radical interpretation and the theory of situated learning, and they are found to be unsound. The article goes on to examine the difficulties involved in combining adequate validity and reliability in one test. The literature on test item formats is brought to bear on the potential validity of multiple-choice items, and the rater reliability of constructed-response items is addressed through discussion of the methods used by the Educational Testing Service (USA) and a summary report of alternative methods developed by the author and others in cooperation with the California Golden State Examination.
High stakes testing and distributive justice
Authors: Schrag Francis K.
Published: October 2004

Evaluation of high stakes testing regimes must consider not simply mean test scores, but their distribution among students. Taking high school graduation tests and black and white student populations to illustrate the argument, I identify two criteria of success: a larger proportion of black high school graduates and a narrower gap between the two groups. I evaluate various possible distributions against these criteria. I then consider the question of which students merit our focused attention, those students who are furthest behind or those with the greatest likelihood of passing the test given extra help. A medical triage analogy suggests we should help the former, but I show here that the analogy is misplaced.
High stakes testing
Authors: Noddings Nel
Published: October 2004

This response argues that, although evaluation of student learning is required for accountability, high stakes testing is not required and may even be counterproductive. It also questions whether the goals of the ‘No Child Left Behind Act’ are reasonable and contends that, if they are not, there may be no justification for imposing punishments and sanctions on children and schools unable to meet them. Moreover, high stakes testing may be incompatible with many defensible aims - among them, critical thinking.
What is at stake in knowing the content and capabilities of children’s minds?
Authors: Norris Stephen P. , Leighton Jacqueline P. , Phillips Linda M.
Published: October 2004

Many significant changes in perspective have to take place before efforts to learn the content and capabilities of children’s minds can hold much sway in educational testing. The language of testing, especially of high stakes testing, remains firmly in the realm of ‘behaviors’, ‘performance’ and ‘competency’ defined in terms of behaviors, test items, or observations. What is on children’s minds is not taken into account as integral to the test design and interpretation process. The point of this article is to argue that behaviorist-based validation models are ill-founded, and to recommend basing tests on cognitive models that theorize the content and capabilities of children’s minds in terms of such features as meta-cognition, reasoning strategies, and principles of sound thinking. This approach is the one most likely to yield the construct validity for tests long endorsed by many testing theorists. The implications of adopting a cognitive basis for testing that might be upsetting to many current practices are explored.
The puzzle of parental partiality
Authors: Macleod Colin M.
Published: October 2004

In this article, I offer a response to Adam Swift’s book, How Not to be A Hypocrite: School Choice for the Morally Perplexed Parent, by developing some reflections on the nature, value and limits of parental partiality. I address two main issues. First, I consider the issue of how we should interpret the character and value of parental partiality. I argue that treating parental partiality as a kind of disposition helps to illuminate its distinctive value and also explains why we tend to judge some illegitimate expressions of partiality more harshly than others. Second, I examine one of the justifications Swift views as valid for sending children to private school. I criticize Swift’s contention that parents can be justified in sending children to private schools in order to secure for them a ‘fair chance in life’.
Quality of Life in Ovarian Cancer Patients: Comparison of Paclitaxel Plus Cisplatin, With Cyclophosphamide Plus Cisplatin in a Randomized Study
Authors: Bezjak Andrea , Tu Dongsheng , Bacon Monica , Osoba David , Zee Benny , Stuart Gavin , Roy Josee-Anne , Piccart Martine , Eisenhauer Elizabeth
Published: October 2004

Purpose

Formal quality-of-life (QOL) assessments may contribute important information on patient symptoms. Despite many trials of systemic chemotherapy in ovarian cancer, reports of its effect on QOL are few.

Patients and Methods

QOL was assessed in an Intergroup randomized trial comparing paclitaxel plus cisplatin to cyclophosphamide plus cisplatin in women with advanced ovarian cancer. One hundred fifty-two eligible patients accrued in Canada completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and a trial-specific checklist at baseline (after surgical debulking) and at regular intervals during and after chemotherapy. Mean change scores over time in the two arms were calculated.

Results

Compliance with QOL questionnaire completion was excellent (81% to 93%). In general, deterioration was seen in the QOL domains immediately after chemotherapy (day 8 of cycle 1), followed by clinically meaningful improvements compared with baseline (change scores ≥ 10) in both arms during the treatment period in a number of domains and items, including global QOL, emotional function, social function, fatigue, pain, sleep, constipation, appetite, abdominal swelling, and abdominal cramps. Improvements in global QOL persisted for the duration of follow-up. More neurosensory effects and myalgia were documented in the paclitaxel arm; however, this did not adversely affect global or other domains of QOL and improved once chemotherapy was completed.

Conclusion

Improvement from baseline in QOL measures was seen in both treatment arms. The greater neurologic and muscle toxicity of paclitaxel did not adversely influence QOL. QOL data can contribute useful information on the experience of symptoms and their time course, which may assist patients and physicians in their discussion about the anticipated effects of therapy.
Hybridization of Surface-modified Semiconductor Nanoparticles and a Resin
Authors: Matsumoto Kazuaki , Tsuji Ryotaro , Yonemushi Yoshiharu , Yoshida Tatsushi
Published: October 2004

A mercapto-terminated linear polymer, which was prepared by a reversible addition-fragmentation chain transfer (RAFT) technique, was used to modify semiconductor nanoparticle surfaces. This modification resulted in an easier dispersion of the nanoparticles in the resins by a simple mixing process, as confirmed by transmission electron microscopy.
Monoallelic Expression of Pax5: A Paradigm for the Haploinsufficiency of Mammalian Pax Genes?
Authors: Nutt S.L. , Busslinger M.
Published: October 2004

It is generally assumed that most mammalian genes are transcribed from both alleles. Hence, the diploid state of the genome offers the advantage that a loss-of-function mutation in one allele can be compensated for by the remaining wild-type allele of the same gene. Indeed, the vast majority of human disease syndromes and engineered mutations in the mouse genome are recessive, indicating that recessiveness is the ‘default’ state. However, a minority of genes are semi-dominant, as heterozygous loss-of-function mutation in these genes leads to phenotypic abnormalities. This condition, known as haploinsufficiency, has been described for five of the nine mammalian
Adeno-Associated Viral Vectors for Gene Transfer and Gene Therapy
Authors: Büeler H.
Published: October 2004

Adeno-associated virus (AAV) is a defective, non-pathogenic human parvovirus that depends for growth on coinfection with a helper adenovirus or herpes virus. Recombinant adeno-associated viruses (rAAVs) have attracted considerable interest as vectors for gene therapy. In contrast to other gene delivery systems, rAAVs lack all viral genes and show long-term gene expression
Histidyl-tRNA Synthetase
Authors: Freist W. , Verhey J.F. , Rühlmann A. , Gauss D.H. , Arnez J.G.
Published: October 2004

Histidyl-tRNA synthetase (HisRS) is responsible for the synthesis of histidyl-transfer RNA, which is essential for the incorporation of histidine into proteins. This amino acid has uniquely moderate basic properties and is an important group in many catalytic functions of enzymes.

A compilation of currently known primary structures of HisRS shows that the subunits of these homodimeric enzymes consist of 420–550 amino acid residues. This represents a relatively short chain length among aminoacyl-tRNA synthetases (aaRS), whose peptide chain sizes range from about 300 to 1100 amino acid residues.

The crystal structures of HisRS from two organisms and their complexes with histidine, histidyl-adenylate and histidinol with ATP have been solved. HisRS from

The aminoacylation reaction follows the standard two-step mechanism. HisRS also belongs to the group of aaRS that can rapidly synthesize diadenosine tetraphosphate, a compound that is suspected to be involved in several regulatory mechanisms of cell metabolism. Many analogs of histidine have been tested for their properties as substrates or inhibitors of HisRS, leading to the elucidation of structure-activity relationships concerning configuration, importance of the carboxy and amino group, and the nature of the side chain.

HisRS has been found to act as a particularly important antigen in autoimmune diseases such as rheumatic arthritis or myositis. Successful attempts have been made to identify epitopes responsible for the complexation with such auto-antibodies.
Dequalinium TM Vesicles Form Stable Complexes with Plasmid DNA which Are Protected from DNase Attack
Authors: Lasch J. , Meye A. , Taubert H. , Koelsch R. , Mansa-ard J. , Weissig V.
Published: October 2004

Upon sonication, the antimicrobial and antineoplastic compound dequalinium

We hypothesize that the DQA/DNA complexes are well-suited for ‘DQAsomal gene transfer’
On the Role of Thymopoietins in Cell Proliferation. Immunochemical Evidence for New Members of the Human Thymopoietin Family
Authors: Weber P.J.A. , Eckard C.P. , Gonser S. , Otto H. , Folkers G. , Beck-Sickinger A.G.
Published: October 2004

Thymopoietins (TMPOs) are a group of ubiquitously expressed nuclear proteins. They are suggested to play an important role in nuclear envelope organization and cell cycle control, as has been shown for lamina-associated polypeptides 2 α and β, which are the rat homologs of human TMPOα and TMPOβ, respectively. The recent isolation and characterization of seven mouse TMPO mRNA transcripts named TMPO-α, β, β', γ, ε, δ, and ζ, suggest that more than the three previously reported transcripts, α, β, and γ forms, may exist in humans. Here we report on the demonstration of putative human TMPOδ and ε by immunoblotting of human cell lines using a newly prepared polyclonal antiserum against the common N-terminal region of TMPO. Furthermore, we prepared the first truly TMPO-β-specific, affinity-purified polyclonal antiserum, using a part of the human analog of the β-specific domain of mouse TMPO 220–259 for immunization. We showed that human TMPOβ is highly expressed in all cancerous cells tested, while hardly any cross-reactivities with other proteins could be detected. In contrast to the high expression of human TMPOβ in the cancer-derived neuroblastoma cell lines SK-N-MC and SMS-KAN, we found very low expression of human TMPOβ in low-proliferative nerve tissue. These data led us to the assumption that expression of TMPOβ may correlate with the occurrence of cancer, and therefore may serve as a new tumor marker, or even as a new target for cancer therapy.
A Non-Radioactive Method for Inexpensive Quantitative RT-PCR
Authors: Maggiolini M. , Donzé O. , Picard D.
Published: October 2004

We present a novel method for quantitative RT-PCR that involves direct incorporation of digoxigenin-11-dUTP (DIG-dUTP) during amplification of cDNAs, separation of RT-PCR products by agarose gel electrophoresis, Southern transfer to a nylon membrane, and chemiluminescent detection with an anti-DIG antibody. The whole procedure can be done in about a day and has the following advantages: It is highly sensitive, specificity is confirmed by monitoring the size of the RT-PCR product, it is non-radioactive, quantitative, and does not require expensive specialized equipment.
Activation of the Transcription Factor ISGF3 by Interferon-gamma
Authors: Matsumoto M. , Tanaka N. , Harada H. , Kimura T. , Yokochi T. , Kitagawa M. , Schindler C. , Taniguchi T.
Published: October 2004

The interferon-stimulated gene factor 3 (ISGF3) transcription factor has been extensively studied in the context of the type I interferon (IFN-α/β)-mediated antiviral response; it consists of the major DNA-binding component p48, and the signal transducers and activators of transcription (Stat)1 and Stat2. We show here that type II IFN (IFN-γ) can also invoke the activation of ISGF3 in mouse primary embryonic fibroblasts. In fact, the two Stat proteins were tyrosine phosphorylated in IFN-γ stimulated cells. Our present findings reveal an additional mechanism by which these two distinct types of cytokines, IFN-α/β and -γ, can commonly elicit antiviral activities.
Human Fc gamma Receptor IIb Expressed in Escherichia coli Reveals IgG Binding Capability
Authors: Sondermann P. , Jacob U.
Published: October 2004

Fcγ receptors (FcγR) are expressed on immunologically active cells where they trigger B and T cell responses and are responsible for the clearance of immunocomplexes. They occur as type I transmembrane proteins and also in soluble forms (sFcR) comprising only the ecto domains of the receptors. State-of-the-art research has generated demand for highly pure and homogeneous sFcγR preparations: first, studies of the immunoregulative potential of the soluble FcγRs have been hampered by co-purified growth factors. Second, they are needed for crystallographic analyses to solve questions such as the exact location of the binding site for IgG on the receptor, and the graded affinities of the receptors for different IgG subclasses. This has been unsuccessful due to limitations in availability and homogeneity of sFcγR expressed in eukaryotic cells. In order to address these problems we expressed the extracellular part of the human Fc-γRIIb inE. coli. The protein was refolded, purified in a three-step procedure and characterized by SDS-PAGE, mass spectrometry as well as N-terminal sequencing. The unglycosylated FcγRIIb is active because it binds immobilized antibody as well as the IgG Fc-fragment in solution. Finally, the receptor was crystallized in orthorhombic, tetragonal and hexagonal crystal forms that diffracted X-rays to resolutions of 1.7 Å, 2.7 Å and 3.8 Å respectively.