Isolated limb perfusion with melphalan for human melanoma xenografts in the hindlimb of nude rats: A surviving animal model

We have established a surviving model of isolated limb perfusion using xenografts of the human melanoma cell line MM 96L injected subcutaneously into the hindlimb of a nude rat, The femoral artery and vein were cannulated via the left renal artery and vein and the hind limb was isolated using tourniquets. The limb was perfused with Krebs Heinseleit buffer at 37 degrees C containing 4.7% bovine serum albumin at a constant flow rate of 4 mi per min for 30-60 min with 100% survival of the animals, Tumour vascularization and blood flow were demonstrated using vascular casts and [Cr-51]-microspheres. Following the addition of melphalan (15 or 100 mu g/ml), drug concentrations in the perfusate, tissues and systemic circulation were determined using high pressure liquid chromatography (HPLC), Systemic leakage, assessed using [I-125]albumin and melphalan and detected by a gamma-counter and HPLC respectively, was <0.5%. The melphalan concentration and tissue flow rate in the tumour deposits were 40 and 30% respectively, when compared with the surrounding subcutaneous tissue, At a dose of 15 mu g/ml, melphalan caused a reduction in tumour growth after 60 min perfusion, and a significant reduction in tumour size was seen when the melphalan dose was 100 mu g/ml. The surviving nude rat model of isolated limb perfusion for recurrent melanoma will allow examination of optimal perfusion conditions, along with the pharmacokinetics, pharmacodynamics and efficacy of melphalan and other drugs.

Effect of the Bloch-Siegert shift in a strongly driven transition: Asymmetric Autler-Townes profile

Under the conditions of the rotating wave approximation (RWA), a transition strongly driven by a resonant oscillating field displays the well known symmetric Autler-Townes doublet. However, if the counter-rotating component, neglected in the RWA, is taken into account, the Bloch-Siegert shift gives rise to an Autler-Townes doublet of unequal intensity even in the case of a resonant driving field. This effect is investigated theoretically in a V-shaped three-level double-resonance configuration and the results are presented in this paper. An interesting observation is that the level of asymmetry not only depends on the driving-field intensity but also on the characteristics of the driven system including relaxation rates and equilibrium population distributions.

On the direct product of two weak uniquely completable partial latin squares

In this note we show by counter-example that the direct product of two weak uniquely completable partial latin squares is not necessarily a uniquely completable partial latin square. This counter-example rejects a conjecture by Gower (see [3]) on the direct product of two uniquely completable partial latin squares.

General strain theory, situational anger, and social networks: An assessment of conditioning influences

Using a random sample of university students to test general strain theory (GST), this study expanded on previous tests of strain theory in two ways. First, situational anger was measured, a construct that had not been used thus far in assessments of general strain. In addition, this research examined the role of social support networks as a conditioning influence on the effects of strain and anger on intentions to commit three types of criminal behavior (serious assault, shoplifting, and driving under the influence of alcohol [DUI]). The results provided mixed support for GST. While the link between anger and crime was confirmed, the nature of that relationship in some cases ran counter to the theory. Moreover, the evidence indicated that the role of social support networks was complex, and varied as a conditioning influence on intentions to engage in criminal activities. (C) 2001 Elsevier Science Ltd. All rights reserved.

Peacebuilding in East Timor

This essay analyses some of the political, economic and social challenges of East Timer's transition to independence. It scrutinizes the ethical dimensions of building peace in a territory devastated by the combined effect of Indonesia's colonial occupation and the violent militia attacks of September 1999. The most difficult task ahead does not lie in the physical rebuilding of the territory-gargantuan as it may be-but in the more intricate and long-term rehabilitation of a traumatized society. The latter involves competing Timorese factions as well as a range of international actors, including the United Nations Transitional Authority, foreign governments, business institutions and various multilateral and bilateral donors. each having their own organizational leitmotifs and policy priorities. If not managed carefully, the reconstruction process could further exacerbate existing societal tensions and complicate the starch for peace and reconciliation. The essay identifies a number of crucial components necessary to counter such risks, including the need to promote popular participation in the rebuilding process. Without the legitimacy created by strong community involvement and grassroots participation in decision making, the task of national reconstruction may well become overwhelmed by conflict.

Guilty? An explanation of the Lockerbie trial. (Case notes)

The Lockerbie Trial, concerning the explosion of Pan Am flight 103 over Lockerbie, Scotland, in 1988, took place in the Netherlands because of the fear that pre-trial publicity would make a fair trial impossible and also fears for the physical safety of the accused - case for the prosecution - application of Scottish law - report of an observer at the trial, Professor Kochler - the International Criminal Court - leave to appeal granted.

Wildlife-based tourism & increased support for nature conservation financially and otherwise: evidence from sea-turtle ecotourism at Mon Repos

The arguments of most conservationists supporting ecotourism have been based on the view that it is environmentally friendly as a resource-use and that receipts from it can counter demands to use the natural resources involved for more extractive economic purposes. But wildlife-based ecotourism can also have positive impacts in itself on the willingness of tourists to pay for wildlife conservation, strengthen the pro-conservation attitudes of tourists, and foster personal actions by them that contribute to wildlife conservation. These aspects are explored in this article on the basis of a survey of tourists visiting Mon Repos Beach near Bundaberg, Queensland, for the purpose of watching marine turtles. The results enable several of the conservation impacts of this experience on tourists to be quantified, and highlight important relationships between specific socio-economic variables and the willingness of tourists to pay for the protection of sea turtles. Furthermore, it is shown that the on-site experiences of ecotourists have positive impacts on the willingness of tourists to pay for the conservation of wildlife, and that willingness to pay is sensitive to whether or not wildlife is seen. It is suggested that in situ ecotourism is likely to be a more powerful force for fostering pro-conservation attitudes and actions among visitors than ex situ wildlife-based tourism in aquaria and zoos.

Effect of chronic clonidine treatment on transmitter release from sympathetic varicosities of the guinea-pig vas deferens

1 Previous studies have demonstrated that chronic pre-synaptic inhibition of transmitter release by morphine evokes a counter-adaptive response in the sympathetic nerve terminals that manifests itself as an increase in transmitter release during acute withdrawal. In the present study we examined the possibility that other pre-synaptically acting drugs such as clonidine also evoke a counter-adaptive response in the sympathetic nerve terminals. 2 In chronically saline treated (CST) preparations, clonidine (0.5 muM) completely abolished evoked transmitter release from sympathetic varicosities bathed in an extracellular calcium concentration ([Ca2+](o)) of 2 mM. The inhibitory effect of clonidine was reduced by increasing [Ca2+](o) from 2 to 4 mM and the stimulation frequency from 0.1 to 1 Hz. 3 The nerve terminal impulse (NTI) was not affected by concentrations of clonidine that completely abolished evoked transmitter release. 4 Sympathetic varicosities developed a tolerance to clonidine (0.5 muM) following 7-9 days of chronic exposure to clonidine. 5 Acute withdrawal of preparations following chronic clonidine treatment (CCT) resulted in a significant (P

Is bucindolol BEST? (A Key Paper Evaluation)

Carvedilol, a non-selective β-adrenoceptor blocker with ancillary properties, and metoprolol and bisoprolol, selective β1-blockers without ancillary properties, have been shown to reduce mortality and morbidity in heart failure. In the Beta-blocker Evaluation of Survival Trial (BEST), bucindolol, a non-selective β-adrenoceptor blocker with different ancillary properties to carvedilol, did not reduce overall survival in heart failure. Possible explanations for this include: more Blacks being included in the trial, bucindolol being more ‘sympatholytic’ than the other β-blockers and more advanced heart failure in BEST. Another possible explanation is that bucindolol is stimulating cardiac β2-adrenoceptors to counter the effects of inhibiting cardiac β1-adrenoceptors. Bucindolol is not the best treatment and carvedilol, metoprolol and bisoprolol should be preferred in heart failure.

The socio-religious beliefs and nature of the contemporary Vampire Subculture

The contemporary Vampire Subculture can be defined as a multi-faceted, socio-religious movement with its own distinct collective community and network of participants who share a similar belief system and customary lifestyle that reflect their concept of the vampire. The Vampire Subculture consists of individuals who profess to be 'real vampires', vampire communities of like-minded persons, 'blood-donors' who willingly allow vampires to partake of them, occult-based and mystical-orientated groups that appeal to their spirituality, the blood fetishists, and the live-action vampire role-players. In response, a Christian counter-movement of self-proclaimed 'vampire-slayers' has emerged that actively opposes the vampire subculture and its beliefs and practices. The socio-religious nature of the Vampire Subculture can be best described as a Segmented, Polycentric and Integrated Network of participants.

Cleaning symbioses from the parasites' perspective

Cleaning behaviour has generally been viewed from the cleaner or client's point of view. Few studies, however, have examined cleaning behaviour from the parasites' perspective, yet they are the equally-important third players in such associations. All three players are likely to have had their evolution affected by the association. As cleaner organisms are important predators of parasites, cleaners are likely to have an important effect on their prey. Little, however, is known of how parasites are affected by cleaning associations and the strategies that parasites use in response to cleaners. I examine here what parasites are involved in cleaning interactions, the effect cleaners have on parasites, the potential counter-adaptations that parasites have evolved against the predatory activities of cleaner organisms, the potential influence of cleaners on the life history traits of parasites, and other factors affected by cleaners. I have found that a wide range of ectoparasites from diverse habitats have been reported to interact with a wide range of cleaner organisms. Some of the life history traits of parasites are consistent with the idea that they are in response to cleaner predation. It is clear, however, that although many cleaning systems exist their ecological role is largely unexplored. This has likely been hindered by our lack of information on the parasites involved in cleaning interactions.

Conceptual modelling and ontology: Possibilities and pitfalls

Conceptual modelling is an activity undertaken during information systems development work to build a representation of selected semantics about some real-world domain. Ontological theories have been developed to account for the structure and behavior of the real world in general. In this paper, I discuss why ontological theories can be used to inform conceptual modelling research, practice, and pedagogy. I provide examples from my research to illustrate how a particular ontological theory has enabled me to improve my understanding of certain conceptual modelling practices and grammars. I describe, also, how some colleagues and I have used this theory to generate several counter-intuitive, sometimes surprising predictions about widely advocated conceptual modelling practices - predictions that subsequently were supported in empirical research we undertook. Finally, I discuss several possibilities and pitfalls I perceived to be associated with our using ontological theories to underpin research on conceptual modelling.

Apocalypse forever? International relations implications of 11 September

This is a contribution to ongoing discussion of the international relations issues raised by the terrorist attacks of 11 September 2001. It acknowledges apparent failings (of analysis or prediction) in the IR literature but then suggests the shortcomings are really the product of divergent traditions of analysis (behaviouralism, structuralism and evolutionism) which isolate different aspects of phenomena for attention. The paper then discusses the contrast between hard power and soft power - to help identify the distinctiveness of the new forms of terrorism (their non-linear objectives and the lack of proportionality involved). It concludes on an encouraging note by urging international cooperation as a solution, even in cases where the protagonists' resentments have tended to militate against conventional channels of dispute resolution.