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

Anthropic solution to the magnetic muon anomaly: the charged see-saw

We present models of new physics that can explain the muon g-2 anomaly in accord with with the assumption that the only scalar existing at the weak scale is the Higgs, as suggested by anthropic selection. Such models are dubbed "charged see-saw" because the muon mass term is mediated by heavy leptons. The electroweak contribution to the g-2 gets modified by order one factors, giving an anomaly of the same order as the observed hint, which is strongly correlated with a modification of the Higgs coupling to the muon.Comment: 21 pages, many equations despite the first word in the title. v3: loop function G_WN corrected, conclusions unchange

Scoring Protein Relationships in Functional Interaction Networks Predicted from Sequence Data

The abundance of diverse biological data from various sources constitutes a rich source of knowledge, which has the power to advance our understanding of organisms. This requires computational methods in order to integrate and exploit these data effectively and elucidate local and genome wide functional connections between protein pairs, thus enabling functional inferences for uncharacterized proteins. These biological data are primarily in the form of sequences, which determine functions, although functional properties of a protein can often be predicted from just the domains it contains. Thus, protein sequences and domains can be used to predict protein pair-wise functional relationships, and thus contribute to the function prediction process of uncharacterized proteins in order to ensure that knowledge is gained from sequencing efforts. In this work, we introduce information-theoretic based approaches to score protein-protein functional interaction pairs predicted from protein sequence similarity and conserved protein signature matches. The proposed schemes are effective for data-driven scoring of connections between protein pairs. We applied these schemes to the Mycobacterium tuberculosis proteome to produce a homology-based functional network of the organism with a high confidence and coverage. We use the network for predicting functions of uncharacterised proteins

Saffold virus is able to productively infect primate and rodent cell lines and induces apoptosis in these cells

10.1038/emi.2014.15Emerging Microbes and Infections3

Validation of the diabetes, hypertension and hyperlipidemia (DHL) knowledge instrument in Malaysia

BACKGROUND: Patient's knowledge on diabetes, hypertension and hyperlipidaemia and its medications can be used as one of the outcome measures to assess the effectiveness of educational intervention. To date, no such instrument has been validated in Malaysia. Therefore, the aim of this study was to evaluate the validity and reliability of the Diabetes, Hypertension and Hyperlipidemia (DHL) knowledge instrument for assessing the knowledge of patients with type 2 diabetes in Malaysia. METHODS: A 28-item instrument which comprised of 5 domains: diabetes, hypertension, hyperlipidemia, medications and general issues was designed and tested. One point was given for every correct answer, whilst zero was given for incorrect answers. Scores ranged from 0 to 28, which were then converted into percentage. This was administered to 77 patients with type 2 diabetes in a tertiary hospital, who were on medication(s) for diabetes and who could understand English (patient group), and to 40 pharmacists (professional group). The DHL knowledge instrument was administered again to the patient group after one month. Excluded were patients less than 18 years old. RESULTS: Flesch reading ease was 60, which is satisfactory, while the mean difficulty factor(SD) was 0.74(0.21), indicating that DHL knowledge instrument was moderately easy. Internal consistency of the instrument was good, with Cronbach's alpha = 0.791. The test-retest scores showed no significant difference for 26 out of the 28 items, indicating that the questionnaire has achieved stable reliability. The overall mean(SD) knowledge scores was significantly different between the patient and professional groups 74.35(14.88) versus 93.84(6.47), p < 0.001. This means that the DHL knowledge instrument could differentiate the knowledge levels of participants. The DHL knowledge instrument shows similar psychometric properties as other validated questionnaires. CONCLUSIONS: The DHL knowledge instrument shows good promise to be adopted as an instrument for assessing diabetic patients' knowledge concerning their disease conditions and medications in Malaysia

Psychometric performance of the CAMPHOR and SF-36 in pulmonary hypertension

BACKGROUND: The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) and the Medical Outcomes Study Short Form 36 (SF-36) are widely used to assess patient-reported outcome in individuals with pulmonary hypertension (PH). The aim of the study was to compare the psychometric properties of the two measures. METHODS: Participants were recruited from specialist PH centres in Australia and New Zealand. Participants completed the CAMPHOR and SF-36 at two time points two weeks apart. The SF-36 is a generic health status questionnaire consisting of 36 items split into 8 sections. The CAMPHOR is a PH-specific measure consisting of 3 scales; symptoms, activity limitations and needs-based QoL. The questionnaires were assessed for distributional properties (floor and ceiling effects), internal consistency (Cronbach's alpha), test-retest reliability and construct validity (scores by World Health Organisation functional classification). RESULTS: The sample comprised 65 participants (mean (SD) age = 57.2 (14.5) years; n(%) male = 14 (21.5%)). Most of the patients were in WHO class 2 (27.7%) and 3 (61.5%). High ceiling effects were observed for the SF-36 bodily pain, social functioning and role emotional domains. Test-retest reliability was poor for six of the eight SF-36 domains, indicating high levels of random measurement error. Three of the SF-36 domains did not distinguish between WHO classes. In contrast, all CAMPHOR scales exhibited good distributional properties, test retest reliability and distinguished between WHO functional classes. CONCLUSIONS: The CAMPHOR exhibited superior psychometric properties, compared with the SF-36, in the assessment of PH patient-reported outcome

WNP: A Novel Algorithm for Gene Products Annotation from Weighted Functional Networks

Predicting the biological function of all the genes of an organism is one of the fundamental goals of computational system biology. In the last decade, high-throughput experimental methods for studying the functional interactions between gene products (GPs) have been combined with computational approaches based on Bayesian networks for data integration. The result of these computational approaches is an interaction network with weighted links representing connectivity likelihood between two functionally related GPs. The weighted network generated by these computational approaches can be used to predict annotations for functionally uncharacterized GPs. Here we introduce Weighted Network Predictor (WNP), a novel algorithm for function prediction of biologically uncharacterized GPs. Tests conducted on simulated data show that WNP outperforms other 5 state-of-the-art methods in terms of both specificity and sensitivity and that it is able to better exploit and propagate the functional and topological information of the network. We apply our method to Saccharomyces cerevisiae yeast and Arabidopsis thaliana networks and we predict Gene Ontology function for about 500 and 10000 uncharacterized GPs respectively

Factors explaining variance in perceived pain in women with fibromyalgia

BACKGROUND: We hypothesized that a substantial proportion of the subjectively experienced variance in pain in fibromyalgia patients would be explained by psychological factors alone, but that a combined model, including neuroendocrine and autonomic factors, would give the most parsimonious explanation of variance in pain. METHODS: Psychometric assessment included McGill Pain Questionnaire, General Health Questionnaire, Hospital Anxiety and Depression Rating Scale, Eysenck personality Inventory, Neuroticism and Lie subscales, Toronto Alexithymia Scale, and Multidimensional Health Locus of Control Scale and was performed in 42 female patients with fibromyalgia and 48 female age matched random sample population controls. A subgroup of the original sample (22 fibromyalgia patients and 13 controls) underwent a pharmacological challenge test with buspirone to assess autonomic and adrenocortical reactivity to serotonergic challenge. RESULTS: Although fibromyalgia patients scored high on neuroticism, anxiety, depression and general distress, only a minor part of variance in pain was explained by psychological factors alone. High pain score was associated with high neuroticism, low baseline cortisol level and small drop in systolic blood pressure after buspirone challenge test. This model explained 41.5% of total pain in fibromyalgia patients. In population controls, psychological factors alone were significant predictors for variance in pain. CONCLUSION: Fibromyalgia patients may have reduced reactivity in the central sympathetic system or perturbations in the sympathetic-parasympathetic balance. This study shows that a biopsychosocial model, including psychological factors as well as factors related to perturbations of the autonomic nervous system and hypothalamic-pituitary-adrenal axis, is needed to explain perceived pain in fibromyalgia patients