Multicenter Blinded Analysis of RT-PCR Detection Methods for Paramyxoviruses in Relation to Paget's Disease of Bone

Conflicting results have been reported on the detection of paramyxovirus transcripts in Paget's disease, and a possible explanation is differences in the sensitivity of RT-PCR methods for detecting virus. In a blinded study, we found no evidence to suggest that laboratories that failed to detect viral transcripts had less sensitive RT-PCR assays, and we did not detect measles or distemper transcripts in Paget's samples using the most sensitive assays evaluated.

Introduction: There is conflicting evidence on the possible role of persistent paramyxovirus infection in Paget's disease of bone (PDB). Some workers have detected measles virus (MV) or canine distemper virus (CDV) transcripts in cells and tissues from patients with PDB, but others have failed to confirm this finding. A possible explanation might be differences in the sensitivity of RT-PCR methods for detecting virus. Here we performed a blinded comparison of the sensitivity of different RT-PCR-based techniques for MV and CDV detection in different laboratories and used the most sensitive assays to screen for evidence of viral transcripts in bone and blood samples derived from patients with PDB.

Materials and Methods: Participating laboratories analyzed samples spiked with known amounts of MV and CDV transcripts and control samples that did not contain viral nucleic acids. All analyses were performed on a blinded basis.

Results: The limit of detection for CDV was 1000 viral transcripts in three laboratories (Aberdeen, Belfast, and Liverpool) and 10,000 transcripts in another laboratory (Manchester). The limit of detection for MV was 16 transcripts in one laboratory (NIBSC), 1000 transcripts in two laboratories (Aberdeen and Belfast), and 10,000 transcripts in two laboratories (Liverpool and Manchester). An assay previously used by a U.S.-based group to detect MV transcripts in PDB had a sensitivity of 1000 transcripts. One laboratory (Manchester) detected CDV transcripts in a negative control and in two samples that had been spiked with MV. None of the other laboratories had false-positive results for MV or CDV, and no evidence of viral transcripts was found on analysis of 12 PDB samples using the most sensitive RT-PCR assays for MV and CDV.

Conclusions: We found that RT-PCR assays used by different laboratories differed in their sensitivity to detect CDV and MV transcripts but found no evidence to suggest that laboratories that previously failed to detect viral transcripts had less sensitive RT-PCR assays than those that detected viral transcripts. False-positive results were observed with one laboratory, and we failed to detect paramyxovirus transcripts in PDB samples using the most sensitive assays evaluated. Our results show that failure of some laboratories to detect viral transcripts is unlikely to be caused by problems with assay sensitivity and highlight the fact that contamination can be an issue when searching for pathogens by sensitive RT-PCR-based techniques.

A cross-national cross-sectional survey of the attitudes and perceived competence of final-year medicine, nursing and pharmacy students in relation to end-of-life care in dementia

Background:Little is known about the attitudes of healthcare professional students' perceived competence and confidence in treating those with dementia who are at the end of life.Aim:To explore the attitudes of final year medical, nursing and pharmacy students towards people with dementia and to evaluate their perceived competence and confidence dealing with biomedical and psychosocial issues within the context of palliative care provision to patients with dementia.Design:Cross-sectional survey using a questionnaire.Setting/participants:Final-year students in each profession from Queen's University Belfast (Northern Ireland) and the University of Iowa (USA) were recruited.Method:Three versions of an online questionnaire (containing the Attitudes to Dementia Questionnaire and a series of questions on end-of-life care in dementia) were distributed.Results:A total of 368 responses were received (response rate 42.3%). All respondents reported positive attitudes towards people with dementia. US nursing students reported significantly more positive attitudes than the medical students of United States and Northern Ireland. Medical students were more likely to report low confidence in discussing non-medical aspects of dying, whereas nursing students were most likely to feel prepared and confident to do this. Medical and nursing students reported low confidence with aspects of medication-related care; however, data from the pharmacy samples of Northern Ireland and United States suggested that these students felt confident in advising other healthcare professionals on medication-related issues.Conclusions:While healthcare students hold positive attitudes towards people with dementia, some clinical tasks remain challenging and further basic training may be of benefit.

Maillard reaction products and their relation to complications in insulin-dependent diabetes mellitus

Glycation, oxidation, and browning of proteins have all been implicated in the development of diabetic complications. We measured the initial Amadori adduct, fructoselysine (FL); two Maillard products, N epsilon-(carboxymethyl) lysine (CML) and pentosidine; and fluorescence (excitation = 328 nm, emission = 378 nm) in skin collagen from 39 type 1 diabetic patients (aged 41.5 +/- 15.3 [17-73] yr; duration of diabetes 17.9 +/- 11.5 [0-46] yr, [mean +/- SD, range]). The measurements were related to the presence of background (n = 9) or proliferative (n = 16) retinopathy; early nephropathy (24-h albumin excretion rate [AER24] > or = 20 micrograms/min; n = 9); and limited joint mobility (LJM; n = 20). FL, CML, pentosidine, and fluorescence increased progressively across diabetic retinopathy (P <0.05, P <0.001, P <0.05, P <0.01, respectively). FL, CML, pentosidine, and fluorescence were also elevated in patients with early nephropathy (P <0.05, P <0.001, P <0.01, P <0.01, respectively). There was no association with LJM. Controlling for age, sex, and duration of diabetes using logistic regression, FL and CML were independently associated with retinopathy (FL odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.01-1.12, P <0.05; CML OR = 6.77, 95% CI = 1.33-34.56, P <0.05) and with early nephropathy (FL OR = 1.05, 95% CI = 1.01-1.10, P <0.05; CML OR = 13.44, 95% CI = 2.00-93.30, P <0.01). The associations between fluorescence and retinopathy and between pentosidine and nephropathy approached significance (P = 0.05). These data show that FL and Maillard products in skin correlate with functional abnormalities in other tissues and suggest that protein glycation and oxidation (glycoxidation) may be implicated in the development of diabetic retinopathy and early nephropathy.

Assessing suspended sediment dynamics in relation to ecological thresholds and sampling strategies in two Irish headwater catchments

Prediction of the impact of suspended sediment on aquatic ecosystems requires adequate knowledge of sediment dynamics in surface waters. Often, studies reporting the response of aquatic biota to suspended sediment are concerned with concentrations, while catchment erosion studies often report sediment delivery as annual loads and yields, making the comparison to documented ecological impacts difficult. Similarly, the European Union Freshwater Fish Directive (FFD) (78/659/EC) stipulates a guideline value of 25mgl which should not be exceeded, with the exception of floods and droughts. In this respect, the significance of suspended sediment in two Irish rivers was assessed using turbidity sensors calibrated for suspended sediment. Sediment yields of 0.07 tonnes (t) hayear and 0.44thayear and annual FFD exceedance frequency of 8.3% and 17.8% were estimated for the two catchments. Contrasts in the frequency of exceedance events between both catchments was observed, yet duration was typically short (

Prenatal and postnatal inflammation in relation to cortisol levels in preterm infants at 18 months corrected age

Objective

To examine whether early inflammation is related to cortisol levels at 18 months corrected age (CA) in children born very preterm.

Study Design

Infants born ≤ 32 weeks gestational age were recruited in the NICU, and placental histopathology, MRI, and chart review were obtained. At 18 months CA developmental assessment and collection of 3 salivary cortisol samples were carried out. Generalized least squares was used to analyze data from 85 infants providing 222 cortisol samples.

Results

Infants exposed to chorioamnionitis with funisitis had a significantly different pattern of cortisol across the samples compared to infants with chorioamnionitis alone or no prenatal inflammation (F[4,139] = 7.3996, P <.0001). Postnatal infections, necrotizing enterocolitis and chronic lung disease were not significantly associated with the cortisol pattern at 18 months CA.

Conclusion

In children born very preterm, prenatal inflammatory stress may contribute to altered programming of the HPA axis.

Keywords: preterm, chorioamnionitis, funisitis, premature infants, hypothalamic-pituitary-adrenal axis, infection, cortisol, stress

Teaching (about) Britishness? An investigation into trainee teachers' understanding of Britishness in relation to citizenship and the discourse of civic nationalism

This research was prompted by the developing political discourse proposing the teaching of Britishness and British values in the context of the United Kingdom. This discourse will be reviewed in the first part of the article, in the context of previous work which has sought to assess how Britishness and related concepts might be promoted through education. The second part will be based on questionnaire responses from a sample of students following post-graduate initial teacher training programmes in a number of higher education partnerships. It indicates that, while political discourse and educational policy have sensitised trainee teachers to the agenda, there remains a deep uncertainty and misgiving about this as an educational objective.

Paraphrasing:Generating parallel programs using refactoring

Refactoring is the process of changing the structure of a program without changing its behaviour. Refactoring has so far only really been deployed effectively for sequential programs. However, with the increased availability of multicore (and, soon, manycore) systems, refactoring can play an important role in helping both expert and non-expert parallel programmers structure and implement their parallel programs. This paper describes the design of a new refactoring tool that is aimed at increasing the programmability of parallel systems. To motivate our design, we refactor a number of examples in C, C++ and Erlang into good parallel implementations, using a set of formal pattern rewrite rules. © 2013 Springer-Verlag Berlin Heidelberg.

Dietary glycemic index and glycemic load in relation to changes in body composition measures during adolescence:Northern Ireland Young Hearts Study

Background: Epidemiologic evidence on the influence of dietary glycemic index (GI) and glycemic load (GL) on the development of obesity is limited.

Objective: This prospective study examined the associations between dietary GI and GL and changes in body composition measures during adolescence.

Design: In a representative sample of Northern Irish adolescents aged 12 years at baseline and 15 years at follow-up (n=426), dietary intake was assessed by a diet history interview. Body composition measures included body mass index (BMI; kg m(-2)), BMI z-score, sum of four skinfold thicknesses, percentage body fat, fat mass index (FMI; kg m(-2)) and fat-free mass index (kg m(-2)).

Results: After adjustment for potential confounding factors, baseline GI was associated with increased change in FMI. Mean (95% confidence interval) values of changes in FMI according to tertiles of baseline GI were 0.41 (0.25, 0.57), 0.42 (0.26, 0.58) and 0.67 (0.51, 0.83) kg m(-2), respectively (P for trend=0.03). There was no significant association of baseline GI with changes in other body composition measures (P for trend0.054). Conversely, baseline GL showed no association with changes in any of the measures (P for trend0.41). Furthermore, changes in GI or GL were not associated with changes in any of the measures (P for trend0.16).

Conclusion: Dietary GI at age 12 years was independently associated with increased change in FMI between ages 12 and 15 years in a representative sample from Northern Ireland, whereas dietary GL showed no association with changes in any of the body composition measures examined.

Creating an Inclusive Society… How Close are We in Relation to Autism Spectrum Disorder? A General Population Survey

BackgroundChildren with autism spectrum disorder are increasingly educated in mainstream classrooms in the United Kingdom (Wilkinson & Twist, Autism and Educational Assessment: UK Policy and Practice. NFER, Slough, 2010), and some employers are now specifically seeking out staff on the autism spectrum. Does that mean that we are living in an inclusive society' [United Nations Department of Economic and Social Affairs (UNDESA), Creating an Inclusive Society: Practical Strategies to Promote Social Integration 2008], in the sense that inequalities are reduced and full economic, social and cultural participation is advanced for individuals with autism?

MethodsA general population survey was conducted to assess how close we, as a society, are to an inclusive society for individuals with autism in Northern Ireland. Public attitudes were examined to (i) visibility and social interaction, (ii) aetiology, needs and interventions, and (iii) rights and resources.

ResultsA stratified, representative sample of 1204 adults took part in the survey; of these, 989 were aware of autism and their attitudes and behavioural projections reflected a mix of acceptance and denunciation. The level of confusion with regard to interventions reflected the general uncertainty within UK policy regarding meeting the needs of individuals on the autism spectrum (International Journal of Disability, Development and Education 61, 134, 2014a).

ConclusionTherefore, it seems that inclusion is working to an extent, but more clarity is needed with regard to adequate education, intervention and support for individuals with autism.