Development and evaluation of a vaginal ring device for sustained delivery of HIV microbicides to non-human primate

Background There is considerable interest in developing coitally indepen- dent, sustained release formulations for long-term administration of HIV microbicides. Vaginal ring devices are at the forefront of this formulation strategy. Methods Non-medicated silicone elastomer vaginal rings were prepared having a range of appropriate dimensions for testing vaginal ?t in pig- tailed and Chinese rhesus macaques. Cervicovaginal proin?ammatory markers were evaluated. Compression testing was performed to compare the relative ?exibility of various macaque and commercial human rings. Results All rings remained in place during the study period and no tissue irritation or signi?cant induction of cervicovaginal proin?ammatory mark- ers or signs of physical discomfort were observed during the 8-week study period. Conclusions Qualitative evaluation suggests that the 25 · 5-mm ring pro- vided optimal ?t in both macaque species. Based on the results presented here, low-consistency silicone elastomers do not cause irritation in maca-

Suggested Binding Mechanism of the HIV-gp120 to its CD4 Receptor

The molecular recognition and attachment of the CD4 molecule and the HIV envelope glycoprotein (gp120) might be described as a consecutive three-step molecular recognition process. 1. (a) Long range interaction: electrostatic pre-orientation, 2. (b) short range interaction: electronic attachment followed by a ‘Locking-in’ (via aromatic ring orientation) and 3. (c) internal interaction (induced fit): conformational readjustment of the protein molecules. On the basis of the preliminary investigations (X-ray structures of CD4 and biological studies of CD4 and gp120 point mutants) we described a computational model. This approach consists of empirical calculations as well as ab initio level of quantum chemistry. The conformational analysis of the wild type and mutant CD4 molecules was supported by molecular mechanics and dynamics (Amber force field). The latter analysis involves the application of a novel method, the Amino Acid Conformation Assignment of Proteins (ACAP) software, developed for the notation of secondary protein structures. According to the cardinal role of the electrostatic factors during this interaction, several ab initio investigations were performed for better understanding of the recognition process on submolecular level. Using the above mentioned computational model, we could interpret the basic behaviours and predict some additional features of CD4-gp120 interaction, in spite of the missing gp120 X-ray structure.

Influence of access to straw provided in racks on the welfare of sows in large dynamic groups

This experiment investigated the effect of providing access to straw in racks on the welfare of sows in large dynamic groups. Two treatments were applied: (1) access to two racks containing chopped barley straw (offering an average of 0.3 kg straw/sow/day) and (2) control, with no straw racks. Treatments were applied to two separate dynamic groups each containing 35 ( 3) sows. Approximately 9 sows were replaced in each of these groups at 3-week intervals (each replacement constituting a replicate of the study). Peak rack usage was shown between 08:00 and 12:00 h, where on average 6% of sows were observed at each rack. On average over a 24-h period, 27% of sows that were observed at the racks were newly introduced. This percentage was significantly greater in the pre- rather than post-feeding yard (P 0.05). A greater proportion of sows performed sham chewing behaviour in the post- rather than the pre-feeding yard (P 0.05). Overall, providing access to straw in racks led to a reduction in pen-directed exploratory behaviour, and this may reflect the fact that sows were provided with an outlet for exploratory and/or foraging behaviour. However, the fact that sham chewing behaviour was not affected suggests that welfare benefits associated with the straw rack treatment were limited. (C) 2007 Elsevier B.V. All rights reserved.

Influence of access to grass silage on the welfare of sows introduced to a large dynamic group

This experiment investigated the effects of providing access to grass silage on the welfare of sows introduced to a large dynamic group. Two treatments were applied: (1) access to racks containing grass silage (offering an average of 1.9 kg silage/sow/day), and (2) control treatment with no grass silage racks. Treatments 1 and 2 were applied to two separate dynamic groups, each containing 37 (2) sows. Approximately 9 sows were replaced in both groups at 3-week intervals, and each of these replacements constituted a replicate of the study. The study was replicated six times using a total of 108 sows. In a time-based cross-over design, treatments were swapped between the two dynamic groups after three replicates. Highest levels of rack usage were shown between 08:00 and 14:00 h. During peak periods, 9.8% of sows were observed at the racks at a given time. On average, 78.5% of sows observed at the racks were newly-introduced animals. Overall levels of aggression to which newly-introduced sows were exposed on the day of introduction to the group were low, and did not differ significantly between treatments (P > 0.05). In addition, injury levels measured 1-week post-introduction to the group did not differ significantly between treatments (P > 0.05). Sham chewing behaviour was more prevalent in the post-rather than the pre-feeding yard (P

To what extent do children with cerebral palsy participate in everyday life situations?

The aims of the study are to describe participation of children with cerebral palsy in everyday life situations, to investigate the relationship between participation (primary outcome variable) with child and parent characteristics (independent variables) and to compare the frequency of participation (secondary outcome variable) of children with cerebral palsy with children without disabilities. A cross-sectional survey of parents of children with cerebral palsy in Northern Ireland was undertaken in families’ homes using standard questionnaires. Children with cerebral palsy born between 31/8/1991 and 1/4/1997 were identified from a case register of people with the condition. A total of 102 parents opted in (51% response rate). Questionnaires included the Life Habits Questionnaire (Life-H) to measure difficulties in participation and The Frequency of Participation Questionnaire (FPQ), to measure frequency of participation with comparative data for children without disability. Overall, children with cerebral palsy participated less often than their non-disabled peers across a number of lifestyle and cultural pursuits. Among the 102 children with cerebral palsy, participation in ‘relationships’ was the least disrupted area of everyday life and aspects of ‘school’, ‘personal care’ and ‘mobility’ were the most disrupted. Children with cerebral palsy and severe co-impairments were significantly less likely to experience higher levels of participation in most areas of everyday life when compared to children with cerebral palsy and no severe co-impairments. Child physical and psychological well-being did not influence participation although higher parenting stress was significantly related to lower child participation in ‘community activities’. Participation is an important health outcome for children with cerebral palsy and should be incorporated in routine clinical practice. Professionals have a role to play both at the level of addressing individual child and family needs as well as influencing legislation and policy to ensure improved access to services and local communities.

New Technology and Researchers’ Access to Court and Tribunal Information: the need for European analysis

We discuss the limitations and rights which may affect the researcher’s access to and use of digital, court and administrative tribunal based information. We suggest that there is a need for a European-wide investigation of the legal framework which affects the researcher who might wish to utilise this form of information. A European-wide context is required because much of the relevant law is European rather than national, but much of the constraints are cultural. It is our thesis that research improves understanding and then improves practice as that understanding becomes part of public debate. If it is difficult to undertake research, then public debate about the court system – its effectiveness, its biases, its strengths – becomes constrained. Access to court records is currently determined on a discretionary basis or on the basis of interpretation of rules of the court where these are challenged in legal proceedings. Anecdotal evidence would suggest that there are significant variations in the extent to which court documents such as pleadings, transcripts, affidavits etc are made generally accessible under court rules or as a result of litigation in different jurisdictions or, indeed, in different courts in the same jurisdiction. Such a lack of clarity can only encourage a chilling of what might otherwise be valuable research. Courts are not, of course, democratic bodies. However, they are part of a democratic system and should, we suggest – both for the public benefit and for their proper operation – be accessible and criticisable by the independent researcher. The extent to which the independent researcher is enabled access is the subject of this article. The rights of access for researchers and the public have been examined in other common law countries but not, to date, in the UK or Europe.

Enabling Free On-line Access to UK Law Reports: The Copyright Problem

The history of publishing legal decisions (law reporting) in the UK has been that of a privatised system since its inception, and that history has encompassed several hundred years. The privatised nature of this has meant that the product (the law report) has been, except in limited cases, viewed as the property of the publisher, rather than the property of the court or public. BAILII is an open access legal database that came about in part because of the copyrighted, privatised nature of this legal information. In this paper, we will outline the problem of access to pre-2000 judgments in the UK and consider whether there are legal or other remedies which might enable BAILII to both develop a richer historic database and also to work in harmony, rather than in competition, with legal publishers. We argue that public access to case law is an essential requirement in a democratic common law system, and that BAILII should be seen as a potential step towards a National Law Library.