Does aspirin or non-aspirin non-steroidal anti-inflammatory drug use prevent colorectal cancer in inflammatory bowel disease?

AIM: To determine whether aspirin or non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAIDs) prevent colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD). METHODS: We performed a systematic review and meta-analysis. We searched for articles reporting the risk of CRC in patients with IBD related to aspirin or NA-NSAID use. Pooled odds ratios (OR) and 95%CIs were determined using a random-effects model. Publication bias was assessed using Funnel plots and Egger’s test. Heterogeneity was assessed using Cochran’s Q and the I2 statistic. RESULTS: Eight studies involving 14917 patients and 3 studies involving 1282 patients provided data on the risk of CRC in patients with IBD taking NA-NSAIDs and aspirin respectively. The pooled OR of developing CRC after exposure to NA-NSAIDs in patients with IBD was 0.80 (95%CI: 0.39-1.21) and after exposure to aspirin it was 0.66 (95%CI: 0.06-1.39). There was significant heterogeneity (I2 > 50%) between the studies. There was no change in the effect estimates on subgroup analyses of the population studied or whether adjustment or matching was performed. CONCLUSION: There is a lack of high quality evidence on this important clinical topic. From the available evidence NA-NSAID or aspirin use does not appear to be chemopreventative for CRC in patients with IBD

Colonic lesion characterization in inflammatory bowel disease: A systematic review and meta-analysis

Aim: To perform a systematic review and meta-analysis for the diagnostic accuracy of in vivo lesion characterization in colonic inflammatory bowel disease (IBD), using optical imaging techniques, including virtual chro-moendoscopy (VCE), dye-based chromoendoscopy (DBC), magnification endoscopy and confocal laser endomicroscopy (CLE). Methods: We searched Medline, Embase and the Cochrane library. We performed a bivariate meta-analysis to calculate the pooled estimate sensitivities, specificities, positive and negative likelihood ratios (+LHR, -LHR), diagnostic odds ratios (DOR), and area under the SROC curve (AUSROC) for each technology group. A subgroup analysis was performed to investigate differences in real-time non-magnified Kudo pit patterns (with VCE and DBC) and real-time CLE. Results: We included 22 studies [1491 patients; 4674 polyps, of which 539 (11.5%) were neoplastic]. Real-time CLE had a pooled sensitivity of 91% (95%CI: 66%-98%), specificity of 97% (95%CI: 94%-98%), and an AUSROC of 0.98 (95%CI: 0.97-0.99). Magnification endoscopy had a pooled sensitivity of 90% (95%CI: 77%-96%) and specificity of 87% (95%CI: 81%-91%). VCE had a pooled sensitivity of 86% (95%CI: 62%-95%) and specificity of 87% (95%CI: 72%-95%). DBC had a pooled sensitivity of 67% (95%CI: 44%-84%) and specificity of 86% (95%CI: 72%-94%). Conclusion: Real-time CLE is a highly accurate technology for differentiating neoplastic from non-neoplastic lesions in patients with colonic IBD. However, most CLE studies were performed by single expert users within tertiary centres, potentially confounding these results

Mga2 transcription factor regulates an oxygen-responsive lipid homeostasis pathway in fission yeast

Eukaryotic lipid synthesis is oxygen-dependent with cholesterol synthesis requiring 11 oxygen molecules and fatty acid desaturation requiring 1 oxygen molecule per double bond. Accordingly, organisms evaluate oxygen availability to control lipid homeostasis. The sterol regulatory element-binding protein (SREBP) transcription factors regulate lipid homeostasis. In mammals, SREBP-2 controls cholesterol biosynthesis, whereas SREBP-1 controls triacylglycerol and glycerophospholipid biosynthesis. In the fission yeast Schizosaccharomyces pombe, the SREBP-2 homolog Sre1 regulates sterol homeostasis in response to changing sterol and oxygen levels. However, notably missing is an SREBP-1 analog that regulates triacylglycerol and glycerophospholipid homeostasis in response to low oxygen. Consistent with this, studies have shown that the Sre1 transcription factor regulates only a fraction of all genes up-regulated under low oxygen. To identify new regulators of low oxygen adaptation, we screened the S. pombe nonessential haploid deletion collection and identified 27 gene deletions sensitive to both low oxygen and cobalt chloride, a hypoxia mimetic. One of these genes, mga2, is a putative transcriptional activator. In the absence of mga2, fission yeast exhibited growth defects under both normoxia and low oxygen conditions. Mga2 transcriptional targets were enriched for lipid metabolism genes, and mga2Δ cells showed disrupted triacylglycerol and glycerophospholipid homeostasis, most notably with an increase in fatty acid saturation. Indeed, addition of exogenous oleic acid to mga2Δ cells rescued the observed growth defects. Together, these results establish Mga2 as a transcriptional regulator of triacylglycerol and glycerophospholipid homeostasis in S. pombe, analogous to mammalian SREBP-1

Harold M. Frost T J Musculoskel Neuron Interact 2001; 2(2):117-119 William F. Neuman Awardee 2001

Tribute to Harold M. Frost, honorary president of ISMNI, who received the William F. Neuman Award from the American Society of Bone and Mineral Research October 2001

The significance of 'the visit' in an English category-B prison: Views from prisoners, prisoners' families and prison staff

A number of claims have been made regarding the importance of prisoners staying in touch with their family through prison visits, firstly from a humanitarian perspective of enabling family members to see each other, but also regarding the impact of maintaining family ties for successful rehabilitation, reintegration into society and reduced re-offending. This growing evidence base has resulted in increased support by the Prison Service for encouraging the family unit to remain intact during a prisoner’s incarceration. Despite its importance however, there has been a distinct lack of research examining the dynamics of families visiting relatives in prison. This paper explores perceptions of the same event – the visit – from the families’, prisoners’ and prison staffs' viewpoints in a category-B local prison in England. Qualitative data was collected with 30 prisoners’ families, 16 prisoners and 14 prison staff, as part of a broader evaluation of the visitors’ centre. The findings suggest that the three parties frame their perspective of visiting very differently. Prisoners’ families often see visits as an emotional minefield fraught with practical difficulties. Prisoners can view the visit as the highlight of their time in prison and often have many complaints about how visits are handled. Finally, prison staff see visits as potential security breaches and a major organisational operation. The paper addresses the current gap in our understanding of the prison visit and has implications for the Prison Service and wider social policy

New machine-marked tests for selection into core medical training: evidence from two validation studies

The objective of this study was to examine whether two machine-marked tests (MMTs), a clinical problem-solving test (CPS) and a situational judgement test (SJT, focusing on professional dilemmas), previously validated for selection into general practice (GP) training in the UK, could provide a valid selection methodology for shortlisting into core medical training (CMT). An exploratory longitudinal design was used to examine the psychometric properties of the MMTs for CMT applicants, and the correlation between MMT scores (time 1) and subsequent CMT interview outcomes (time 2). Independent samples from two consecutive years were used: in 2008 a retrospective analysis of data was used, while in 2009, doctors applying for CMT were asked to complete the MMTs for evaluation purposes. In 2008, a total of 1,711 doctors applied to both CMT and GP training and completed the MMTs. In 2009, a total of 2,265 doctors who applied for CMT completed the MMTs for evaluation purposes. The main outcome measure was the CMT applicants’ interview score. Both the CPS and SJT had good reliability and score distributions for 2008 and 2009 CMT samples, similar to the GP comparison samples. The MMTs were good predictors of performance in the CMT interviews (r0.56, p0.001 in 2008, and r0.61, p0.001 in 2009 for both MMTs combined) and offered incremental validity over the current shortlisting process. The GP MMTs offer an appropriate measurement methodology for selection into CMT, representing a significant innovation for developing selection methodology for CMT. Longer-term studies should be undertaken to assess the validity of all selection techniques used, in terms of CMT training outcome

Ambient particulate pollution and the world-wide prevalence of asthma, rhinoconjunctivitis and eczema in children: Phase One of the International Study of Asthma and Allergies in Childhood (ISAAC)

Objectives: To investigate the effect of ambient particulate matter on variation in childhood prevalence of asthma, rhinoconjunctivitis and eczema. Methods: Prevalences of asthma, rhinoconjunctivitis and eczema obtained in Phase One of the International Study of Asthma and Allergies in Childhood (ISAAC) were matched with city-level estimates of residential PM10 obtained from a World Bank model. Associations were investigated using binomial regression adjusting for GNP per capita and for clustering within country. For countries with more than one centre, a two stage meta-analysis was carried out. The results were compared with a meta-analysis of published multi-centre studies. Results: Annual concentrations of PM₁₀ at city level were obtained for 105 ISAAC centres in 51 countries. After controlling for GNP per capita, there was a weak negative association between PM₁₀ and various outcomes. For severe wheeze in 13-14-year-olds, the OR for a 10 μg/m³ increase in PM₁₀ was 0.92 (95 CI 0.84 to 1.00). In 24 countries with more than one centre, most summary estimates for within-country associations were weakly positive. For severe wheeze in 13-14-year-olds, the summary OR for a 10 μg/m³ increase in PM₁₀ was 1.01 (0.92 to 1.10). This result was close to a summary OR of 0.99 (0.91 to 1.06) obtained from published multi-centre studies. Conclusions: Modelled estimates of particulate matter at city level are imprecise and incomplete estimates of personal exposure to ambient air pollutants. Nevertheless, our results together with those of previous multi-centre studies, suggest that urban background PM₁₀ has little or no association with the prevalence of childhood asthma, rhinoconjunctivitis or eczema either within or between countries

Barriers and enablers to diabetic retinopathy screening attendance: Protocol for a systematic review

BACKGROUND: Diabetic retinopathy is a serious complication of diabetes which, if left untreated, can result in blindness. Population screening among people with diabetes has been shown to be clinically effective; however, suboptimal attendance with wide demographic disparities has been reported. To develop quality improvement interventions to maximise attendance, it is important to understand the theoretical determinants (i.e. barriers and enablers) of screening behaviour. The aim of this systematic review is to identify and synthesise the modifiable barriers and enablers associated with diabetic retinopathy screening attendance. METHODS/DESIGN: Primary and secondary studies will be included if they report perceived barriers/enablers of diabetic retinopathy screening attendance, from the perspectives of people with diabetes and healthcare providers. There will be no restrictions on study design. Studies will be identified from published and grey literature through multiple sources. Bibliographic databases will be searched using synonyms in four search domains: diabetic retinopathy; screening; barriers/enablers; and theoretical constructs relating to behaviour. Search engines and established databases of grey literature will be searched to identify additional relevant studies. Extracted data will include: participant quotations from qualitative studies, statistical analyses from questionnaire and survey studies, and interpretive descriptions and summaries of results from reports. All extracted data will be coded into domains from the Theoretical Domains Framework (TDF) and (for organisational level data) the Consolidated Framework of Implementation Research (CFIR); with domains representing theoretical barriers/enablers proposed to mediate behaviour change. The potential role of each domain in influencing retinopathy screening attendance will be investigated through thematic analysis of the TDF/ CFIR coding. Domain importance will be identified using pre-specified criteria: "frequency" and "expressed importance". Variations in perceived barriers and enablers between demographic groups (e.g., socio-economic, ethnic) will be explored. DISCUSSION: This review will identify important barriers and enablers likely to influence attendance for diabetic retinopathy screening. The results will be used to assess the extent to which existing interventions targeting attendance address the theoretical determinants of attendance behaviour. Findings will inform recommendations for future intervention design. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016032990

Reducing bias in auditory duration reproduction by integrating the reproduced signal

Duration estimation is known to be far from veridical and to differ for sensory estimates and motor reproduction. To investigate how these differential estimates are integrated for estimating or reproducing a duration and to examine sensorimotor biases in duration comparison and reproduction tasks, we compared estimation biases and variances among three different duration estimation tasks: perceptual comparison, motor reproduction, and auditory reproduction (i.e. a combined perceptual-motor task). We found consistent overestimation in both motor and perceptual-motor auditory reproduction tasks, and the least overestimation in the comparison task. More interestingly, compared to pure motor reproduction, the overestimation bias was reduced in the auditory reproduction task, due to the additional reproduced auditory signal. We further manipulated the signal-to-noise ratio (SNR) in the feedback/comparison tones to examine the changes in estimation biases and variances. Considering perceptual and motor biases as two independent components, we applied the reliability-based model, which successfully predicted the biases in auditory reproduction. Our findings thus provide behavioral evidence of how the brain combines motor and perceptual information together to reduce duration estimation biases and improve estimation reliability

Distortions of Subjective Time Perception Within and Across Senses

Background: The ability to estimate the passage of time is of fundamental importance for perceptual and cognitive processes. One experience of time is the perception of duration, which is not isomorphic to physical duration and can be distorted by a number of factors. Yet, the critical features generating these perceptual shifts in subjective duration are not understood. Methodology/Findings: We used prospective duration judgments within and across sensory modalities to examine the effect of stimulus predictability and feature change on the perception of duration. First, we found robust distortions of perceived duration in auditory, visual and auditory-visual presentations despite the predictability of the feature changes in the stimuli. For example, a looming disc embedded in a series of steady discs led to time dilation, whereas a steady disc embedded in a series of looming discs led to time compression. Second, we addressed whether visual (auditory) inputs could alter the perception of duration of auditory (visual) inputs. When participants were presented with incongruent audio-visual stimuli, the perceived duration of auditory events could be shortened or lengthened by the presence of conflicting visual information; however, the perceived duration of visual events was seldom distorted by the presence of auditory information and was never perceived shorter than their actual durations. Conclusions/Significance: These results support the existence of multisensory interactions in the perception of duration and, importantly, suggest that vision can modify auditory temporal perception in a pure timing task. Insofar as distortions in subjective duration can neither be accounted for by the unpredictability of an auditory, visual or auditory-visual event, we propose that it is the intrinsic features of the stimulus that critically affect subjective time distortions