Calibration of myocardial T2 and T1 against iron concentration.

BACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron. METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy. RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001). CONCLUSION: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies

Biopsy-based calibration of T2* magnetic resonance for estimation of liver iron concentration and comparison with R2 Ferriscan.

BACKGROUND: There is a need to standardise non-invasive measurements of liver iron concentrations (LIC) so clear inferences can be drawn about body iron levels that are associated with hepatic and extra-hepatic complications of iron overload. Since the first demonstration of an inverse relationship between biopsy LIC and liver magnetic resonance (MR) using a proof-of-concept T2* sequence, MR technology has advanced dramatically with a shorter minimum echo-time, closer inter-echo spacing and constant repetition time. These important advances allow more accurate calculation of liver T2* especially in patients with high LIC. METHODS: Here, we used an optimised liver T2* sequence calibrated against 50 liver biopsy samples on 25 patients with transfusional haemosiderosis using ordinary least squares linear regression, and assessed the method reproducibility in 96 scans over an LIC range up to 42 mg/g dry weight (dw) using Bland-Altman plots. Using mixed model linear regression we compared the new T2*-LIC with R2-LIC (Ferriscan) on 92 scans in 54 patients with transfusional haemosiderosis and examined method agreement using Bland-Altman approach. RESULTS: Strong linear correlation between ln(T2*) and ln(LIC) led to the calibration equation LIC = 31.94(T2*)-1.014. This yielded LIC values approximately 2.2 times higher than the proof-of-concept T2* method. Comparing this new T2*-LIC with the R2-LIC (Ferriscan) technique in 92 scans, we observed a close relationship between the two methods for values up to 10 mg/g dw, however the method agreement was poor. CONCLUSIONS: New calibration of T2* against liver biopsy estimates LIC in a reproducible way, correcting the proof-of-concept calibration by 2.2 times. Due to poor agreement, both methods should be used separately to diagnose or rule out liver iron overload in patients with increased ferritin

Dual oscillator model of the respiratory neuronal network generating quantal slowing of respiratory rhythm

We developed a dual oscillator model to facilitate the understanding of dynamic interactions between the parafacial respiratory group (pFRG) and the preBötzinger complex (preBötC) neurons in the respiratory rhythm generation. Both neuronal groups were modeled as groups of 81 interconnected pacemaker neurons; the bursting cell model described by Butera and others [model 1 in Butera et al. (J Neurophysiol 81:382–397, 1999a)] were used to model the pacemaker neurons. We assumed (1) both pFRG and preBötC networks are rhythm generators, (2) preBötC receives excitatory inputs from pFRG, and pFRG receives inhibitory inputs from preBötC, and (3) persistent Na+ current conductance and synaptic current conductances are randomly distributed within each population. Our model could reproduce 1:1 coupling of bursting rhythms between pFRG and preBötC with the characteristic biphasic firing pattern of pFRG neurons, i.e., firings during pre-inspiratory and post-inspiratory phases. Compatible with experimental results, the model predicted the changes in firing pattern of pFRG neurons from biphasic expiratory to monophasic inspiratory, synchronous with preBötC neurons. Quantal slowing, a phenomena of prolonged respiratory period that jumps non-deterministically to integer multiples of the control period, was observed when the excitability of preBötC network decreased while strengths of synaptic connections between the two groups remained unchanged, suggesting that, in contrast to the earlier suggestions (Mellen et al., Neuron 37:821–826, 2003; Wittmeier et al., Proc Natl Acad Sci USA 105(46):18000–18005, 2008), quantal slowing could occur without suppressed or stochastic excitatory synaptic transmission. With a reduced excitability of preBötC network, the breakdown of synchronous bursting of preBötC neurons was predicted by simulation. We suggest that quantal slowing could result from a breakdown of synchronized bursting within the preBötC

SNPs Occur in Regions with Less Genomic Sequence Conservation

Rates of SNPs (single nucleotide polymorphisms) and cross-species genomic sequence conservation reflect intra- and inter-species variation, respectively. Here, I report SNP rates and genomic sequence conservation adjacent to mRNA processing regions and show that, as expected, more SNPs occur in less conserved regions and that functional regions have fewer SNPs. Results are confirmed using both mouse and human data. Regions include protein start codons, 3′ splice sites, 5′ splice sites, protein stop codons, predicted miRNA binding sites, and polyadenylation sites. Throughout, SNP rates are lower and conservation is higher at regulatory sites. Within coding regions, SNP rates are highest and conservation is lowest at codon position three and the fewest SNPs are found at codon position two, reflecting codon degeneracy for amino acid encoding. Exon splice sites show high conservation and very low SNP rates, reflecting both splicing signals and protein coding. Relaxed constraint on the codon third position is dramatically seen when separating exonic SNP rates based on intron phase. At polyadenylation sites, a peak of conservation and low SNP rate occurs from 30 to 17 nt preceding the site. This region is highly enriched for the sequence AAUAAA, reflecting the location of the conserved polyA signal. miRNA 3′ UTR target sites are predicted incorporating interspecies genomic sequence conservation; SNP rates are low in these sites, again showing fewer SNPs in conserved regions. Together, these results confirm that SNPs, reflecting recent genetic variation, occur more frequently in regions with less evolutionarily conservation

The respiratory research agenda in primary care in Portugal: a Delphi study

Background: A research agenda can help to stimulate and guide research. The International Primary Care Respiratory Group (IPCRG) published a Research Needs Statement (RNS) in 2010 in which 145 research questions were identified. In 2012, priorities for respiratory research were established, based on these questions. To date, there has been no statement on primary care respiratory research needs in Portugal. The aim of the study was to develop a national consensus on research priorities in respiratory diseases in primary care in Portugal and to assess the applicability of the priorities for respiratory research set by the IPCRG. Method: We conducted a Delphi study by electronic mail with a panel of experts on respiratory disease from primary and secondary care in Portugal. In the first round, the research needs in respiratory disease in Portugal were identified. In the second round, 196 research questions in six disease areas, derived from the first round and from the IPCRG Respiratory needs statement, were prioritised on a five-point Likert-type scale. In the third round, the questions were prioritized again with feed-back provided on the median scores for each item in the second round. Consensus was considered to have been reached when 80 % of the participants gave a score of 4 or 5 out of five on a given item. Results: The 40 experts identified 121 respiratory research questions in Round 1 and expressed their views on 196 questions in Rounds 2 and 3. Twelve research questions (6 %) reached consensus. There were five questions in the asthma domain on early diagnosis, pulmonary function tests, the use of inhalers, and adherence to treatment. There were four questions in the chronic obstructive pulmonary disease domain on vaccinations, on routine monitoring and evaluation of treatment, on diagnosis, and on adherence to treatments. There was one question in the smoking domain on the effects of brief counselling. There were two questions on respiratory tract infections on the treatment of children and on the prescription of antibiotics. An additional 23 research questions (12 %) achieved consensus between 75 and 79 %. Conclusion: The results reflect the Portuguese reality in response the international agenda for research on respiratory diseases published by the IPCRG. They can support the development of future respiratory disease research in Portugal.Financial support for this work was provided by FEDER funds through the Operational Programme Competitiveness Factors - COMPETE and National Funds through FCT - Foundation for Science and Technology under the project POCI-01-0145-FEDER-007038; and by the project NORTE-01-0145-FEDER-000013, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). PMT is partially supported by a grant from the International Primary Care Respiratory Group

Validation of a new test that assesses functional performance of the upper extremity and neck (FIT-HaNSA) in patients with shoulder pathology

<p>Abstract</p> <p>Background</p> <p>There is a lack of standardized tests that assess functional performance for sustained upper extremity activity. This study describes development of a new test for measuring functional performance of the upper extremity and neck and assesses reliability and concurrent validity in patients with shoulder pathology.</p> <p>Methods</p> <p>A series of developmental tests were conducted to develop a protocol for assessing upper extremity tasks that required multi-level movement and sustained elevation. Kinematics of movement were investigated to inform subtask structure. Tasks and test composition were refined to fit clinical applicability criteria and pilot tested on 5 patients awaiting surgery for shoulder impingement and age-sex matched controls. Test-retest reliability was assessed on 10 subjects. Then a cohort of patients with mild to moderate (n = 17) shoulder pathology and 19 controls (17 were age-sex matched to patients) were tested to further validate the Functional Impairment Test-Hand, and Neck/Shoulder/Arm (FIT-HaNSA) by comparing it to self-reported function and measured strength. The FIT-HaNSA, DASH and SPADI were tested on a single occasion. Impairments in isometric strength were measured using hand-held dynamometry. Discriminative validity was determined by comparing scores to those of age-sex matched controls (n = 34), using ANOVA. Pearson correlations between outcome measures (n = 41) were examined to establish criterion and convergent validity.</p> <p>Results</p> <p>A test protocol based on three five-minute subtasks, each either comprised of moving objects to waist-height shelves, eye-level shelves, or sustained manipulation of overhead nuts/bolts, was developed. Test scores for the latter 2 subtasks (or total scores) were different between controls as compared to either surgical-list patients with shoulder impingement or a variety of milder shoulder pathologies (p < 0.01). Test 1 correlated the highest with the DASH (r = -0.83), whereas Test 2 correlated highest with the SPADI (r = -0.76).</p> <p>Conclusion</p> <p>Initial data suggest the FIT-HaNSA provides valid assessment of impaired functional performance in patients with shoulder pathology. It discriminates between patients and controls, is related to self-reported function, and yet provides distinct information. Longitudinal testing is warranted.</p

Can Research Assessments Themselves Cause Bias in Behaviour Change Trials? A Systematic Review of Evidence from Solomon 4-Group Studies

BACKGROUND: The possible effects of research assessments on participant behaviour have attracted research interest, especially in studies with behavioural interventions and/or outcomes. Assessments may introduce bias in randomised controlled trials by altering receptivity to intervention in experimental groups and differentially impacting on the behaviour of control groups. In a Solomon 4-group design, participants are randomly allocated to one of four arms: (1) assessed experimental group; (2) unassessed experimental group (3) assessed control group; or (4) unassessed control group. This design provides a test of the internal validity of effect sizes obtained in conventional two-group trials by controlling for the effects of baseline assessment, and assessing interactions between the intervention and baseline assessment. The aim of this systematic review is to evaluate evidence from Solomon 4-group studies with behavioural outcomes that baseline research assessments themselves can introduce bias into trials. METHODOLOGY/PRINCIPAL FINDINGS: Electronic databases were searched, supplemented by citation searching. Studies were eligible if they reported appropriately analysed results in peer-reviewed journals and used Solomon 4-group designs in non-laboratory settings with behavioural outcome measures and sample sizes of 20 per group or greater. Ten studies from a range of applied areas were included. There was inconsistent evidence of main effects of assessment, sparse evidence of interactions with behavioural interventions, and a lack of convincing data in relation to the research question for this review. CONCLUSIONS/SIGNIFICANCE: There were too few high quality completed studies to infer conclusively that biases stemming from baseline research assessments do or do not exist. There is, therefore a need for new rigorous Solomon 4-group studies that are purposively designed to evaluate the potential for research assessments to cause bias in behaviour change trials

Estimating the prevalence of food risk increasing behaviours in UK kitchens

© 2017 Jones et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Foodborne disease poses a serious threat to public health. In the UK, half a million cases are linked to known pathogens and more than half of all outbreaks are associated with catering establishments. The UK Food Standards Agency (FSA) has initiated the UK Food Hygiene Rating Scheme in which commercial food establishments are inspected and scored with the results made public. In this study we investigate the prevalence of food risk increasing behaviours among chefs, catering students and the public. Given the incentive for respondents to misreport when asked about illegal or illicit behaviours we employed a Randomised Response Technique designed to elicit more accurate prevalence rates of such behaviours. We found 14% of the public not always hand-washing immediately after handling raw meat, poultry or fish; 32% of chefs and catering students had worked within 48 hours of suffering from diarrhoea or vomiting. 22% of the public admitted having served meat “on the turn” and 33% of chefs and catering students admitted working in kitchens where such meat was served; 12% of the public and 16% of chefs and catering students admitted having served chicken at a barbeque when not totally sure it was fully cooked. Chefs in fine-dining establishment were less likely to wash their hands after handling meat and fish and those who worked in award winning restaurants were more likely to have returned to work within 48 hours of suffering from diarrhoea and vomiting. We found no correlation between the price of a meal in an establishment, nor its Food Hygiene Rating Score, and the likelihood of any of the food malpractices occurring