Inbreeding depression by environment interactions in a free-living mammal population.

Experimental studies often find that inbreeding depression is more severe in harsh environments, but the few studies of in situ wild populations available to date rarely find strong support for this effect. We investigated evidence for inbreeding depression by environment interactions in nine traits in the individually monitored Soay sheep population of St Kilda, using genomic inbreeding coefficients based on 37 037 single-nucleotide polymorphism loci, and population density as an axis of environmental variation. All traits showed variation with population density and all traits showed some evidence for depression because of either an individual's own inbreeding or maternal inbreeding. However, only six traits showed evidence for an interaction in the expected direction, and only two interactions were statistically significant. We identify three possible reasons why wild population studies may generally fail to find strong support for interactions between inbreeding depression and environmental variation compared with experimental studies. First, for species with biparental inbreeding only, the amount of observed inbreeding in natural populations is generally low compared with that used in experimental studies. Second, it is possible that experimental studies sometimes actually impose higher levels of stress than organisms experience in the wild. Third, some purging of the deleterious recessive alleles that underpin interaction effects may occur in the wild.

Do I have enough time? The impact of recruiting patients to a randomised controlled trial at recruiting centres.

INTRODUCTION: This paper explores the impact of recruiting patients to a randomised controlled trial (RCT) at recruiting centres. This large multicentre RCT examining the efficacy of chewing gum compared to ibuprofen in the relief of orthodontic pain was carried out across nine recruiting centres. METHOD: The work diaries of clinicians and supporting staff at recruiting centres were analysed over a four-month period from September to December 2011. This quantified the amount of clinical and non-clinical time spent on research duties. RESULTS: Over this time period 98 patients were recruited across seven trial sites. On average, patient recruitment had a direct clinical impact of 19 minutes per patient recruited. The time commitment on trial administration outside the clinical sessions was much higher, averaging at 110 minutes per patient recruited, giving the overall time spent on the trial 129 minutes per patient. CONCLUSIONS: This information will be valuable to lead researchers when calculating the full economic cost of a proposed clinical trial and therefore when applying for grant funding. It may also be valuable to clinicians and their managers when considering becoming a principle investigator (PI) in a RCT. Although the impact on clinical time was 19 minutes per patient recruited, there is a considerably higher (almost six times greater) time commitment in administration around the recruitment of patients.

Does articulating study casts make a difference to treatment planning?

OBJECTIVE: To assess whether articulating casts in centric relation (CR) compared with intercuspal position (ICP) makes a difference to treatment planning. DESIGN: Reliability analysis. SUBJECTS: Ten orthodontists. METHODS: Twenty case vignettes were examined on three occasions: twice with the casts in ICP and once in CR. A series of dichotomous decisions were made relating to the treatment need and treatment mechanics. MAIN OUTCOME MEASURES: The changes in treatment decisions were examined. Intra-examiner agreement between the two hand-held cast assessments (H1 v. H2) and between the first set of hand-held casts compared with the articulated casts (H1 v. A1) were evaluated using the kappa statistic. The differences between the kappa statistics for H1 v. H2 and H1 v. A1 were then tested with the Wilcoxon matched pairs signed rank sum test. RESULTS: The only statistically significant change in the kappa score between H1 v. H2 and H1 v. A1 was for the extraction decision (P= 0.007). No other statistically significant differences were found for the other treatment decisions, although trends were identified for orthognathic surgery and anchorage support decisions. CONCLUSION: Routine articulation of study models for all orthodontic patients is not supported by the results of this study. Articulation of the study models did not affect the treatment planning decisions in a meaningful manner. Further work with selected samples is required to determine if articulation is helpful for specific malocclusions.

Mutation testing in Treacher Collins Syndrome.

OBJECTIVE: To report on a study where 97 subjects were screened for mutations in the Treacher Collins syndrome (TCS) gene TCOF1. METHOD: Ninety-seven subjects with a clinical diagnosis of TCS were screened for potential mutations in TCOF1, by means of single strand conformation polymorphism (SSCP) analysis. In those subjects where potential mutations were detected, sequence analysis was performed to determine the site and type of mutation present. RESULTS: Thirty-six TCS-specific mutations are reported including 27 deletions, six point mutations, two splice junction mutations, and one insertion/deletion. This brings the total number of mutations reported to date to 105. CONCLUSION: The importance of detection of these mutations is mainly in postnatal diagnosis and genetic counselling. Knowledge of the family specific mutation may also be used in prenatal diagnosis to confirm whether the foetus is affected or not, and give the parents the choice of whether to continue with the pregnancy.

The role of p53 and Ki67 in Paget's disease of the vulva and the breast.

OBJECTIVE: Paget's disease of the vulva (PDV) and Paget's disease of the breast (PDB) are uncommon diseases, accounting for approximately 1% of all vulval neoplasms and 0.5-4% of all breast cancers, respectively. In 10-30% of vulval cases an invasive adenocarcinoma is present. In such cases the disease is often aggressive and recurrence rate is high. This is in contrast to PDB where the general consensus is that almost all cases are associated with an in situ or invasive ductal carcinoma. Our aim was to examine the presence of the tumor suppressor protein p53 and the proliferation marker Ki67 in PDV and PDB and correlate any differences in the expression of these two proteins with the presence of an underlying carcinoma. METHODS: Immunohistochemistry was performed on 52 archival cases of PDV, which included 10 with associated invasive adenocarcinoma of the vulva, and on 37 archival cases of PDB, including 26 with available associated ductal carcinoma in situ (DCIS) or invasive carcinoma of the breast. All cases were formalin-fixed and paraffin wax-embedded. Monoclonal antibodies were used with microwave antigen retrieval. Streptavidin-biotin-horseradish peroxidase and 3,3'-diaminobenzidine detection methods were employed to visualize antibody binding and staining. A section was scored positive for p53 if more than 10% of cell nuclei were stained brown and Ki67 was expressed as a percentage of positive cells to the nearest 5% of cells showing nuclear positivity (Ki67 staining index). RESULTS: p53 was expressed in 15 of 52 (29%) PDV cases and 5 of 37 (13%) cases of PDB. Four of the ten cases (40%) of PDV associated with invasive disease expressed p53 compared with 11 of 42 (26%) cases without invasive disease. The mean Ki67 staining index for PDV associated with invasion was 19%, and for that without invasion, 16%. In the breast cases, the mean staining index was 11%. CONCLUSION: Our data suggest that p53 may have a role to play in PDV progression, and may be a late event in some cases, especially those associated with invasive disease. Ki67 has no apparent prognostic role in PDV as there was no significant difference between those cases associated with and those without invasive disease. Neither p53 nor Ki67 appears to have a prognostic role to play in PDB.

So you want to be a specialist registrar?--What to put in your CV.

Dentists applying to a specialist training programme often receive conflicting advice over what to put in their curriculum vitae (CV). We conducted a survey of the Training Programme Directors of the dental specialties to determine what aspects of CV content and presentation styles are considered important. This has allowed us to construct guidelines for what to put in a CV. Recently, structured application forms have become increasingly popular and may be a more objective way to carry out the shortlisting process. The guidelines presented could also be used as a framework for medical personnel departments if structured application forms eventually replace the CV.

Running patterns of transfemoral amputees: a clinical analysis.

The challenge of rehabilitating young, healthy transfemoral amputees may extend beyond the boundaries of teaching them to adapt to functional activities of daily living. The goal for several of these amputees is to participate and sometimes even compete in recreational activities, including running. These amputee runners require prosthetic adaptations as well as a comprehensive individualized training programme to ensure that their running is as safe and energy efficient as possible. To help amputees achieve this, clinicians must understand normal and prosthetic locomotion. This paper compares the biomechanical differences between walking and running in normal locomotion and analyses the running modes used by transfemoral amputees. The modified running mode achieved with the Terry Fox Running Prosthesis subjectively "looks" more energy efficient to the observer and "feels" more energy efficient to the user. These assumptions have yet to be confirmed or refuted by a rigorous scientific research study. An outline of the proposed physiotherapy protocol includes the familiarization, treatment, and training phases. Physiotherapists involved in amputation rehabilitation may not be commonly confronted with this level of patient expectation. It is their responsibility to give realistic guidance to these amputees so that they can safely and independently pursue their recreational running activities. This need can best be fulfilled by providing sound clinical advice which has been validated by research findings.

Sulfur base ligation to iron(II) and cobalt(II) porphyrins.

Equilibrium constants for the binding of sulfur bases to cobalt(II) porphyrins were measured in toluene solution by a spectrophotometric method. The order of decreasing binding strength of sulfur ligands to cobalt(II) porphyrins was found to be mercaptide ions >> thioethers > mercaptans. It is suggested that a similar stability order of these sulfur ligands should exist towards iron(II) porphyrins, but formation constants could be obtained only for the mercaptide ions.

Insect hormones: olive oil is not an inert vehicle for hormone injection into locusts.

Like other fatty oils from plants, olive and peanut oils, the most commonly used vehicles for the injection of juvenile hormone and its analogs, contain substances that show effects similar to those of this hormone. A dose of olive oil smaller than that used to dissolve a single injection of juvenile hormone will cause nuclear enlargement in the cells of the prothoracic gland of the desert locus and advance the succeeding molt.

Bracken and locust ecdysones: their effects on molting in the desert locust.

Bracken contains ecdysone derivatives that are active when injected into locusts. However, when fed to the desert locust as its sole or chief diet, it does not affect molting, growth, or development. There is evidence that, in locusts, the active ecdysones are dehydroxylated to (alpha)-ecdysone and passed out through the gut in the feces. There is no evidence for any uptake of ecdysones from the gut.