The impact of offering multiple cervical screening options to women whose screening was overdue in Dumfries and Galloway, Scotland.

Most women who develop cancer have not been screened regularly. One in four women in Scotland, is overdue for cervical screening. Aim was to assess the impact of offering multiple cervical screening options to women whose screening is overdue. A prospective cohort study including all women whose screening was overdue, aged 30-60 years in Dumfries and Galloway in 2012. Potentially eligible women (n = 4146) were identified split into six groups. Women aged 30-55 years were allocated to three different groups. Group 1 (letter, n = 1246), Group 2 (letter and kit, n = 221), Group 3 (letter, n = 2031). Women aged 56-60 years were allocated to: Group 4 (letter, n = 292), Group 5 (letter and kit, n = 292) and Group 6 (control, n = 64). Women who self-collected a vaginal sample were requested to complete a questionnaire. The percentages of women responding were 24 % (21-26), 32 % (25-38), 16 % (14-18), 15 % (11-20) and 12 % (9-17) in groups 1 to 5 respectively, compared with 3 % (0-11) among controls. A significantly higher number of women (n = 383, 10 % of 3815) opted for self-sampling in comparison with undergoing a cervical screening test (CST) at the GP practice (n = 197, 5 %, x2 = 59.0, p < 0.0001). The Evalyn® Brush was well accepted (218/313 = 70 %) by those who requested self-sampling. Almost all (265/272 = 97 %) women who self-collected a vaginal sample said that if they had the option of self-sampling, they would regularly participate in future cervical screening. Offering more flexible screening options, self-sampling in particular, appears to increase cervical screening participation.

Practical learning through radiation physics problem solving.

INTRODUCTION: The identification of unknown radionuclides is an authentic practical activity for students that provides the foundations for clinical problem solving, especially in the storage and management of radioactive waste. As different radionuclides have different half-lives, some of which are quite long, the storage of waste material has to accommodate the longest of these. Cross contamination requires a method of identifying the radionuclide samples in a mixed sample to safely and appropriately manage disposal. Similarly, identifying a single unknown sample of a radionuclide allows correct handling and disposal. METHODS: Performing a systematic investigation of the physical properties of unknown radioactive samples is a rich learning opportunity to instil understanding of important physics principles among students in nuclear medicine. RESULTS: This manuscript outlines an investigation developed that would allow students to identify single unknown radionuclides based on physical properties and identify the constituent radionuclides of a mixed sample using some additional mathematical curve stripping. CONCLUSION: The processes and solutions are provided with real data and this practical activity can be replicated by students generating their own data. IMPLICATIONS FOR PRACTICE: This paper provides a template and analysis/interpretation guideline for educators and clinicians to deepen understanding of foundation physics. Enhanced and deeper understanding are a vehicle for improved problem solving in clinical and research practice.

Dexamethasone-related adrenal insufficiency in patients with brain and skull base tumours.

PURPOSE: This study aimed to evaluate the prevalence of glucocorticoid-induced adrenal insufficiency in a cohort of patients with brain and skull base tumours and to identify factors which may predict its occurrence. METHODS: Patients with brain or skull base tumours attending for a short synacthen test (SST) (adrenocorticotropin hormone (ACTH) stimulation test) at a single institution over a 3-year period were retrospectively identified. Baseline demographics and dexamethasone exposure were examined. Only patients with dexamethasone exposure were included in the final analysis looking at the primary end point of SST failure. Fisher's exact test, Student's t test, Mann-Whitney test and the Kendall's tau-b test were used to evaluate the influence of age, gender, diagnosis and mean pituitary radiation dose on the primary endpoint. Receiver operating characteristic (ROC) curves were generated to explore the impact of duration and total exposure to dexamethasone on likelihood of SST failure. RESULTS: Thirty-one of 51 patients with previous dexamethasone exposure failed their first SST (61%). No significant relationship was demonstrated between age, gender, diagnosis or mean pituitary radiation dose and SST failure. Duration of and total exposure to dexamethasone were significantly associated with SST failure (p = 0.001 and p = 0.007, respectively). ROC curves generated values of 78 days and 171 mg days to give a sensitivity of 94 and 97%, respectively, to detect SST failure. CONCLUSIONS: Duration of dexamethasone use and total exposure predict for adrenal insufficiency in patients with brain and skull base tumours. Values derived from this study may be useful to identify patients at higher risk of adrenal suppression who require empirical hydrocortisone pending formal testing of the hypothalamic-pituitary-adrenal axis.

Early markers of allergic disease in a primary prevention study using probiotics: 2.5-year follow-up phase.

BACKGROUND: We previously reported that a Lactobacillus acidophilus probiotic strain (LAFTI) L10/LAVRI-A1) given for the first 6 months of life increased the risk of allergen sensitization at 1 year of age. METHODS: To assess the effects on subsequent allergic outcomes, 153 children from the initial prevention cohort (n = 178) were reviewed at 2.5 years of age. Clinical outcomes were assessed in relation to (i) probiotic supplementation; and (ii) immune function previously assessed at 6 months of age. RESULTS: Supplementation with this probiotic did not reduce the risk of dermatitis at 2.5 years (31/74, 42%) compared with that in placebo group (25/76, 34%). There was no significant reduction in any other allergic disease or allergen sensitization. Inhalant sensitization at 2.5 years (n = 29) was associated with higher proportions of circulating CD4+ CD25+ regulatory T-cell populations (P = 0.005) and higher allergen-induced FOXP3 levels (P = 0.003) at 6 months. This was also seen in children with dermatitis. Children with dermatitis at 2.5 years also had significantly lower toll-like receptor 4 lipopolysaccharide responses at 6 months of age (IL-12 P = 0.04, IL-6 P = 0.039) and lower polyclonal (PHA) responses (IFN-gamma P = 0.005, IL-10 P = 0.001, and IL-6 P = 0.001). Children who had previously received the probiotic had fewer gastrointestinal infections in the preceding 18 months (P = 0.023). CONCLUSION: The LAFTI L10 probiotic strain did not have any significant effect on allergy outcomes. Allergic children showed a number of early differences in immune function including altered regulatory T-cell markers and innate immune function.

Supplementation with Lactobacillus rhamnosus or Bifidobacterium lactis probiotics in pregnancy increases cord blood interferon-gamma and breast milk transforming growth factor-beta and immunoglobin A detection.

BACKGROUND: This study explored the effects of maternal probiotic supplementation on immune markers in cord blood (CB) and breast milk. METHODS: CB plasma and breast milk samples were collected from a cohort of women who had received daily supplements of either 6 x 10(9) CFU/day Lactobacillus rhamnosus HN001 (n=34), 9 x 10(9) CFU/day Bifidobacterium lactis HN019 (n=35) or a placebo (n=36) beginning 2-5 weeks before delivery and continuing for 6 months in lactating women. CB plasma and breast milk (collected at 3-7 days, 3 months and 6 months postpartum) were assayed for cytokines (IL-13, IFN-gamma, IL-6, TNF-alpha, IL-10, TGF-beta1) and sCD14. Breast milk samples were also assayed for total IgA. RESULTS: Neonates of mothers who received a probiotic had higher CB IFN-gamma levels (P=0.026), and a higher proportion had detectable blood IFN-gamma levels, compared with the placebo group (P=0.034), although levels were undetectable in many infants. While this pattern was evident for both probiotics, when examined separately only the L. rhamnosus HN001 group showed statistically significant higher IFN-gamma levels (P=0.030) compared with the placebo group. TGF-beta1 levels were higher in early breast milk (week 1) from the probiotic groups (P=0.028). This was evident for the B. lactis HN019 group (P=0.041) with a parallel trend in the L. rhamnosus HN001 group (P=0.075). Similar patterns were seen for breast milk IgA, which was more readily detected in breast milk from both the B. lactis HN019 (P=0.008) and the L. rhamnosus HN001 group (P=0.011). Neonatal plasma sCD14 levels were lower in the B. lactis HN019 group compared with the placebo group (P=0.041). CONCLUSION: The findings suggest that supplementation with probiotics in pregnancy has the potential to influence fetal immune parameters as well as immunomodulatory factors in breast milk.

Relationship between early intestinal colonization, mucosal immunoglobulin A production and systemic immune development.

BACKGROUND: Variations in early intestinal colonization patterns have been implicated in the predispostion to allergic disease through effects on mucosal and systemic immune function. METHODS: Colonization patterns and mucosal IgA production at 6 months of age were examined in relation to early exposures, systemic immune development and early allergic outcomes. This was performed in a cohort (n=189) who had received either Lactobacillus acidophilus or a placebo since birth. RESULTS: Children who developed sensitization to one or more allergens by 12 months of age had significantly higher total (but not secretory) IgA levels at 6 months (P=0.024), but this was independent of probiotic treatment. There were no relationships between colonization patterns and IgA (total or secretory IgA) levels or allergic outcomes (sensitization, atopic dermatitis or food allergies). Breastfeeding, and the use of yoghurt or probiotic supplements were independently associated with significantly higher proportions of 'favourable' lactobacilli and bifidobacteria species. Caesarean delivery and the use of antibiotics during the first 6 months were not associated with significant variations in colonization. Higher proportions of 'favourable' bacteria (notably bifidobacteria) were associated with reduced production of most cytokine response to allergens, but increased expression of regulatory cell markers (P=0.009) and transforming growth factor-beta (P=0.016). CONCLUSION: 'Favourable' colonization, particularly with bifidobacteria, was associated with effects on cellular immune function, but this was not associated with mucosal immunity (secretory IgA) or reduced risk of allergic disease.

Prevalence of gca, a gene involved in synthesis of A-band common antigen polysaccharide in Pseudomonas aeruginosa.

Two distinct forms of lipopolysaccharide are expressed by Pseudomonas aeruginosa. These forms are known as the A band and the B band. In an attempt to obtain a better understanding of A-band lipopolysaccharide synthesis, a previously isolated A-band gene known as the gca gene (GDP-D-mannose conversion protein for A-band common antigen polysaccharide) was sequenced and analyzed. Previous protein expression data from our laboratory, along with nucleotide sequence analysis from the present study, suggest that the Gca protein is encoded by the open reading frame ORF36.5. Amino acid homology reveals that this protein may be functioning as a dehydratase or as a bifunctional enzyme, facilitating the conversion of GDP-D-mannose to GDP-D-rhamnose. The distribution of this gca gene among the 20 P. aeruginosa O serotypes, clinical isolates, and other Pseudomonas species was also examined. Southern hybridization results revealed that the gca gene is present and conserved on a 1.6-kb KpnI fragment among all 20 O serotypes with the exception of serotype O12. In addition, the gca gene is not universally found among all pseudomonads; however, probe-reactive profiles are similar to that of P. aeruginosa when the gca gene is present. Primers were designed from the gca nucleotide sequence, and PCR amplification of a 700-bp product was found with each of the 20 O serotypes. Because of the conservation of this gene, gca may be useful as a diagnostic tool for detecting the presence of P. aeruginosa as well as other Pseudomonas species.

Inter-observer variability in the assessment of nerve function in leprosy patients in Ethiopia.

One of the major problems in leprosy is to detect any change in nerve function early enough so as to increase the chances of recovery and prevent disability. Several tests have been developed to assess nerve function and are used in leprosy control programs worldwide, but they are frequently performed by different workers on different occasions and under variable conditions. In this study we investigated the variability between different groups of observers in the assessment of nerve function in leprosy patients in Ethiopia. Sensory function was assessed by using a set of nylon monofilaments (NF) and a ball-point pen (BP), and motor function was assessed by using voluntary motor testing (VMT). We also studied the variability between observers in the assessment of the clinical signs of neuritis. Duplicate measurements were performed in random order on 50 leprosy patients by two physio-technicians and on 50 other patients by two health assistants. The percent agreement between observers was calculated for each single nerve, and weighted kappa statistics were used to assess whether agreement was better than expected due to chance alone. Systematic differences between observers were evaluated using the Wilcoxon signed rank test. On sensory testing, inter-observer variability was found to be related to the training and experience of the observer, to the nerve tested, and to the neurological status of the patient. When tests were performed by physio-technicians, we observed 32% to 58% agreement with the NF test and 71% to 84% agreement with the BP test, measured on different scales. After weighting for the scale difference, the agreement seemed comparable with these methods but the differences in measurements with the BP test were found to be dependent upon the neurological status of the patient. The variability between observers differed according to the nerve tested, and there was some evidence of systematic differences between observers with both methods. When performed by the health assistants, agreement was between 34% and 46% with the NF and between 66% and 82% with the BP tests. After weighting for the scale difference, the agreement seemed comparable but the BP was not liable to the systematic differences seen in the NF results. These differences could be attributed to the differences in the experience of the workers with these tests. With the VMT, small variability between observers was found for all nerves tested, except the facial nerve, when performed by both the physio-technicians and by the health assistants (72% to 98% agreement).(ABSTRACT TRUNCATED AT 400 WORDS)

Lipid and Surface Wax Synthesis in Water-stressed Cotton Leaves.

The incorporation of [2-(14)C]malonate and [1-(14)C]acetate into internal lipid and surface wax by cotton leaves (Gossypium hirsutum L. ;Deltapine') having water potentials of -8 to -15 bars (controls) and -19 to -32 bars (water-stressed) was compared. Lipid from stressed leaves contained a mean of 57% more radioactivity than corresponding controls for five experiments. Acetyl coenzyme A carboxylase was not limiting to fatty acid synthesis in water-stressed cotton leaves at the water potential levels tested, whereas fatty acid synthetase was stimulated. In four of six experiments, wax from stressed leaves contained a mean of 38% less radioactivity than nonstressed leaves when incubated 24 hours after rehydration. Evidence is presented to show that after a suitable period of rehydration, previously stressed cotton leaves produce more wax than leaves prior to stressing.