SWAT-1: The effectiveness of a 'site visit' intervention on recruitment rates in a multi-centre randomised trial

Background: Recruitment rates in multi-centre randomised trials often fall below target recruitment rates, causing problems for study outcomes. The Studies Within A Trial (SWAT) Programme, established by the All-Ireland Hub for Trials Methodology Research in collaboration with the Medical Research Council Network of Hubs in the United Kingdom and others, is developing methods for evaluating aspects of trial methodology through the conduct of research within research. A recently published design for a SWAT-1 provides a protocol for evaluating the effect of a site visit by the principal investigator on recruitment in multi-centre trials.

Methods: Using the SWAT-1 design, the effect of a site visit, with the sole purpose of discussing trial recruitment, on recruitment rates in a large multicentre trial in the Republic of Ireland was evaluated. A controlled before and after intervention comparison was used, where the date of the site visit provides the time point for the intervention, and for the comparison to control sites. Site A received the intervention. Site B and Site C acted as the controls. Z-scores for proportions were calculated to determine within site recruitment differences. Odds ratios and 95% confidence intervals were calculated to determine between site recruitment differences.

Results: Recruitment rates were increased in Site A post-intervention (17% and 14% percentage point increases at 1 and 3 months, respectively). No differences in recruitment occurred in Site B or in Site C. Comparing between site differences, at 3 months post-intervention, a statistically significant difference was detected in favour of higher recruitment in Site A (34% versus 25%; odds ratio 1.57, 95% confidence interval 1.09 to 2.26).

Conclusions: This is the first reported example of a study in the SWAT programme.. It provides evidence that a site visit, combined with a scheduled meeting, increases recruitment in a clinical trial. Using this example, other researchers might be encouraged to consider conducting a similar study, allowing the findings of future SWAT-1s to be compared and combined, so that higher level evidence on the effect of a site visit by the principal investigator can be obtained.

First record of minimum Irish hare (Lepus timidus hibernicus Bell 1837) longevity in the wild.

Average longevity of the mountain hare (Lepus timidus L., 1758) has been estimated at nine years in the wild (Macdonald D. and Barrett, P. 1993 Mammals of Britain and Europe. Harper Collins Publishers, London) with a maximum recorded age of 18 years for one marked animal (Angerbjörn, A. and Flux, J. E. C. 1995 Lepus timidus. Mammalian Species 495: 1–11). However, the longevity of the Irish hare (L. t. hibernicus Bell 1837) is entirely unknown. A total of 14 Irish hares was trapped and tagged at Belfast International Airport, Co. Antrim from February to April 2005. The sex, age (juvenile or adult) and weight of each animal were recorded. Adults were taken as those individuals >8-10 months old defined by the fusing of the notch between the apophysis and diaphysis of the tibia and humerus (Flux, J. E. C. 1970 Journal of Zoology 161: 75-123). Individual identification was made by a system of colourcoded ear tags (Roxan iD Ltd. Selkirk, Scotland) being inserted in the centre of the pinna of each ear. Each ear tag (6 × 34 mm) and puncture site was disinfected with 70 per cent ethanol prior to insertion. An adult male, #001/002 ‘Blue/Blue’, was tagged on 3 March 2005 weighing 3.8 kg and was sighted during a return site visit on 4 April 2007. An adult female, #026/003 ‘Green/Yellow’, was tagged on 15 April 2005 weighing 4.0 kg and was sighted during return visits on 25 March 2010 and 19 October 2010. The latest possible date of birth for both individuals was spring/summer 2004. Consequently, they were at least 3 years and 6.5 years old, respectively. This is the first record of minimum Irish hare longevity in the wild. These observations suggest that ear tagging does not compromise animal welfare and is an effective means of long-term monitoring. Future research may utilize capture-mark-recapture methods.

Developing a methodology for the National Frog Survey of Ireland: a pilot study in Co. Mayo.

A National Frog Survey of Ireland is planned for spring 2011. We conducted a pilot survey of 25 water bodies in ten 0.25 km2 survey squares in Co. Mayo during spring 2010. Drainage ditches were the most commonly available site for breeding and, generally, two 100 m stretches of ditch were surveyed in each square. The restricted period for peak spawning activity renders any methodology utilizing only one site visit inherently risky. Consequently, each site was visited three times from late March to early April. Occurrence of spawn declined significantly from 72 % to 44 % between the first and third visit whilst the overall occurrence of spawn at all sites was 76 %. As the breeding season advanced, spawn either hatched or was predated and, therefore, disappeared. In those water bodies where spawning was late, however, greater densities of spawn were deposited than in those sites where breeding was early. Consequently, spawn density and estimated frog density did not differ significantly between site visits. Future surveys should nevertheless include multiple site visits to avoid biased estimation of species occurrence and distribution. Ecological succession was identified as the main threat present at 44 % of sites.

Sleeping site selection by the golden-handed tamarin Saguinus midas midas: The role of predation risk, proximity to feeding sites, and territorial defence

Tamarin monkeys, of the genus Saguinus, spend over half their lives at arboreal sleeping sites. The decision as to which site to use is likely to have considerable fitness consequences. These decisions about sleeping sites by three troops of golden-handed tamarin Saguinus midas midas were examined over a 9-mo period at a rainforest site in French Guiana. Data are presented on the physical nature of sleeping sites, their number, position within home ranges, and pattern of use and reuse, aspects of behaviour at retirement and egress, and predation attempts on the study troops. Cumulative plot analysis indicated that a tamarin troop used 30-40 sleeping sites in a 100-day period, approximately half of which were used very infrequently, so that consecutive reuse was never greater than three nights. Sleeping trees were superior in architectural parameters and liana weight to non-sleeping trees. There were no more sleeping sites than expected within the home range boundary region of the tamarins or in areas of overlap with the home ranges of neighbouring troops. Tamarins selected sleeping sites nearest to the last feeding site of the day on 25% of occasions. The study troops engaged in a number of activities that may reduce predation risk; raptor attacks on the study troops over 9 mo were frequent but unsuccessful. Tamarins often visited a sleeping site several hours before arrival, and were more likely to visit a site before use if they had not used it recently. The decision to select a sleeping site therefore involved knowledge of the previous frequency of use of that site.

The conserved Helix C region in the superfamily of interferon-a/interleukin-10-related cytokines corresponds to a high-affinity binding site for the HSP70 chaperone DnaK.

HSP70 chaperones mediate protein folding by ATP-dependent interaction with short linear peptide segments that are exposed on unfolded proteins. The mode of action of the Escherichia coli homolog DnaK is representative of all HSP70 chaperones, including the endoplasmic reticulum variant BiP/GRP78. DnaK has been shown to be effective in assisting refolding of a wide variety of prokaryotic and eukaryotic proteins, including the -helical homodimeric secretory cytokine interferon- (IFN-). We screened solid-phase peptide libraries from human and mouse IFN- to identify DnaK-binding sites. Conserved DnaK-binding sites were identified in the N-terminal half of helix B and in the C-terminal half of helix C, both of which are located at the IFN- dimer interface. Soluble peptides derived from helices B and C bound DnaK with high affinity in competition assays. No DnaK-binding sites were found in the loops connecting the -helices. The helix C DnaK-binding site appears to be conserved in most members of the superfamily of interleukin (IL)-10-related cytokines that comprises, apart from IL-10 and IFN-, a series of recently discovered small secretory proteins, including IL-19, IL-20, IL-22/IL-TIF, IL-24/MDA-7 (melanoma differentiation-associated gene), IL-26/AK155, and a number of viral IL-10 homologs. These cytokines belong to a relatively small group of homodimeric proteins with highly interdigitated interfaces that exhibit the strongly hydrophobic character of the interior core of a single-chain folded domain. We propose that binding of DnaK to helix C in the superfamily of IL-10-related cytokines may constitute the hallmark of a novel conserved regulatory mechanism in which HSP70-like chaperones assist in the formation of a hydrophobic dimeric "folding" interface.