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

Key features of palliative care service delivery to Indigenous peoples in Australia, New Zealand, Canada and the United States: A comprehensive review

Background: Indigenous peoples in developed countries have reduced life expectancies, particularly from chronic diseases. The lack of access to and take up of palliative care services of Indigenous peoples is an ongoing concern. Objectives: To examine and learn from published studies on provision of culturally safe palliative care service delivery to Indigenous people in Australia, New Zealand (NZ), Canada and the United States of America (USA); and to compare Indigenous peoples’ preferences, needs, opportunities and barriers to palliative care. Methods: A comprehensive search of multiple databases was undertaken. Articles were included if they were published in English from 2000 onwards and related to palliative care service delivery for Indigenous populations; papers could use quantitative or qualitative approaches. Common themes were identified using thematic synthesis. Studies were evaluated using Daly’s hierarchy of evidence-for-practice in qualitative research. Results: Of 522 articles screened, 39 were eligible for inclusion. Despite diversity in Indigenous peoples’ experiences across countries, some commonalities were noted in the preferences for palliative care of Indigenous people: to die close to or at home; involvement of family; and the integration of cultural practices. Barriers identified included inaccessibility, affordability, lack of awareness of services, perceptions of palliative care, and inappropriate services. Identified models attempted to address these gaps by adopting the following strategies: community engagement and ownership; flexibility in approach; continuing education and training; a whole-of-service approach; and local partnerships among multiple agencies. Better engagement with Indigenous clients, an increase in number of palliative care patients, improved outcomes, and understanding about palliative care by patients and their families were identified as positive achievements. Conclusions: The results provide a comprehensive overview of identified effective practices with regards to palliative care delivered to Indigenous populations to guide future program developments in this field. Further research is required to explore the palliative care needs and experiences of Indigenous people living in urban areas

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

The Effect of Plant Inbreeding and Stoichiometry on Interactions with Herbivores in Nature: Echinacea angustifolia and Its Specialist Aphid

Fragmentation of once widespread communities may alter interspecific interactions by changing genetic composition of interacting populations as well as their abundances and spatial distributions. In a long-term study of a fragmented population of Echinacea angustifolia, a perennial plant native to the North American prairie, we investigated influences on its interaction with a specialist aphid and tending ants. We grew plant progeny of sib-matings (I), and of random pairings within (W) and between (B) seven remnants in a common field within 8 km of the source remnants. During the fifth growing season, we determined each plant's burden of aphids and ants, as well as its size and foliar elemental composition (C, N, P). We also assayed composition (C, N) of aphids and ants. Early in the season, progeny from genotypic classes B and I were twice as likely to harbor aphids, and in greater abundance, than genotypic class W; aphid loads were inversely related to foliar concentration of P and positively related to leaf N and plant size. At the end of the season, aphid loads were indistinguishable among genotypic classes. Ant abundance tracked aphid abundance throughout the season but showed no direct relationship with plant traits. Through its potential to alter the genotypic composition of remnant populations of Echinacea, fragmentation can increase Echinacea's susceptibility to herbivory by its specialist aphid and, in turn, perturb the abundance and distribution of aphids

Extreme Evolutionary Disparities Seen in Positive Selection across Seven Complex Diseases

Positive selection is known to occur when the environment that an organism inhabits is suddenly altered, as is the case across recent human history. Genome-wide association studies (GWASs) have successfully illuminated disease-associated variation. However, whether human evolution is heading towards or away from disease susceptibility in general remains an open question. The genetic-basis of common complex disease may partially be caused by positive selection events, which simultaneously increased fitness and susceptibility to disease. We analyze seven diseases studied by the Wellcome Trust Case Control Consortium to compare evidence for selection at every locus associated with disease. We take a large set of the most strongly associated SNPs in each GWA study in order to capture more hidden associations at the cost of introducing false positives into our analysis. We then search for signs of positive selection in this inclusive set of SNPs. There are striking differences between the seven studied diseases. We find alleles increasing susceptibility to Type 1 Diabetes (T1D), Rheumatoid Arthritis (RA), and Crohn's Disease (CD) underwent recent positive selection. There is more selection in alleles increasing, rather than decreasing, susceptibility to T1D. In the 80 SNPs most associated with T1D (p-value <7.01×10−5) showing strong signs of positive selection, 58 alleles associated with disease susceptibility show signs of positive selection, while only 22 associated with disease protection show signs of positive selection. Alleles increasing susceptibility to RA are under selection as well. In contrast, selection in SNPs associated with CD favors protective alleles. These results inform the current understanding of disease etiology, shed light on potential benefits associated with the genetic-basis of disease, and aid in the efforts to identify causal genetic factors underlying complex disease

Welfare conditionality and social marginality: the folly of the tutelary state?

In a contemporarnb 1`vby evolution of the tutelary state, welfare reform in the United Kingdom has been characterised by moves towards greater conditionality and sanctioning. This is influenced by the attributing responsibility for poverty and unemployment to the behaviour of marginalised individuals. Mead (1992) has argued that the poor are dependants who ought to receive support on condition of certain restrictions imposed by a protective state that will incentivise engagement with support mechanisms. This article examines how the contemporary tutelary and therapeutic state has responded to new forms of social marginality. Drawing on a series of in-depth interviews conducted with welfare claimants with an offending background in England and Scotland, the article examines their encounters with the welfare system and argues that alienation, rather than engagement with support, increasingly characterises their experiences

Novel catalytically active pd/Ru bimetallic nanoparticles synthesized by Bacillus benzeovorans

This work was supported by a UK Commonwealth scholarship to JBO. BK was supported by the Petroleum Technology Development Funds (PTDF) of Nigeria. The project was funded by NERC grant NE/L014076/1 to LEM. The Science City Photoemission Facility used in this research was funded through the Science Cities Advanced Materials Project 1: Creating and Characterizing Next Generation of Advanced Materials with support from AWM and ERDF funds. The microscopy work was conducted in the “Laboratorio de Microscopias Avanzadas” at “Instituto de Nanociencia de Aragon - Universidad de Zaragoza” Spain. The authors acknowledge the LMA-INA for offering access to their instruments and expertise.Bacillus benzeovorans assisted and supported growth of ruthenium (bio-Ru) and palladium/ruthenium (bio-Pd@Ru) core@shell nanoparticles (NPs) as bio-derived catalysts. Characterization of the bio-NPs using various electron microscopy techniques and high-angle annular dark field (HAADF) analysis confirmed two NP populations (1–2 nm and 5–8 nm), with core@shells in the latter. The Pd/Ru NP lattice fringes, 0.231 nm, corresponded to the (110) plane of RuO2. While surface characterization using X-ray photoelectron spectroscopy (XPS) showed the presence of Pd(0), Pd(II), Ru(III) and Ru(VI), X-ray absorption (XAS) studies of the bulk material confirmed the Pd speciation (Pd(0) and Pd(II)- corresponding to PdO), and identified Ru as Ru(III) and Ru(IV). The absence of Ru–Ru or Ru–Pd peaks indicated Ru only exists in oxide forms (RuO2 and RuOH), which are surface-localized. X ray diffraction (XRD) patterns did not identify Pd-Ru alloying. Preliminary catalytic studies explored the conversion of 5-hydroxymethyl furfural (5-HMF) to the fuel precursor 2,5-dimethyl furan (2,5-DMF). Both high-loading (9.7 wt.% Pd, 6 wt.% Ru) and low-loading (2.4 wt.% Pd, 2 wt.% Ru) bio-derived catalysts demonstrated high conversion efficiencies (~95%) and selectivity of ~63% (~20% better than bio-Ru NPs) and 58%, respectively. These materials show promising future scope as efficient low-cost biofuel catalysts.Funded by NERC grant NE/L014076/

Assessment of Metabolic Phenotypes in Patients with Non-ischemic Dilated Cardiomyopathy Undergoing Cardiac Resynchronization Therapy

Studies of myocardial metabolism have reported that contractile performance at a given myocardial oxygen consumption (MVO2) can be lower when the heart is oxidizing fatty acids rather than glucose or lactate. The objective of this study is to assess the prognostic value of myocardial metabolic phenotypes in identifying non-responders among non-ischemic dilated cardiomyopathy (NIDCM) patients undergoing cardiac resynchronization therapy (CRT). Arterial and coronary sinus plasma concentrations of oxygen, glucose, lactate, pyruvate, free fatty acids (FFA), and 22 amino acids were obtained from 19 male and 2 female patients (mean age 56 ± 16) with NIDCM undergoing CRT. Metabolite fluxes/MVO2 and extraction fractions were calculated. Flux balance analysis (FBA) was performed with MetaFluxNet 1.8 on a metabolic network of the cardiac mitochondria (189 reactions, 230 metabolites) reconstructed from mitochondrial proteomic data (615 proteins) from human heart tissue. Non-responders based on left ventricular ejection fraction (LVEF) demonstrated a greater mean FFA extraction fraction (35% ± 17%) than responders [18 ± 10%, p = 0.0098, area under the estimated ROC curve (AUC) was 0.8238, S.E. 0.1115]. Calculated adenosine triphosphate (ATP)/MVO2 using FBA correlated with change in New York Heart Association (NYHA) class (rho = 0.63, p = 0.0298; AUC = 0.8381, S.E. 0.1316). Non-responders based on both LVEF and NYHA demonstrated a greater mean FFA uptake/MVO2 (0.115 ± 0.112) than responders (0.034 ± 0.030, p = 0.0171; AUC = 0.8593, S.E. 0.0965). Myocardial FFA flux and calculated maximal ATP synthesis flux using FBA may be helpful as biomarkers in identifying non-responders among NIDCM patients undergoing CRT

The devil is in the details: trends in avoidable hospitalization rates by geography in British Columbia, 1990–2000

BACKGROUND: Researchers and policy makers have focussed on the development of indicators to help monitor the success of regionalization, primary care reform and other health sector restructuring initiatives. Certain indicators are useful in examining issues of equity in service provision, especially among older populations, regardless of where they live. AHRs are used as an indicator of primary care system efficiency and thus reveal information about access to general practitioners. The purpose of this paper is to examine trends in avoidable hospitalization rates (AHRs) during a period of time characterized by several waves of health sector restructuring and regionalization in British Columbia. AHRs are examined in relation to non-avoidable and total hospitalization rates as well as by urban and rural geography across the province. METHODS: Analyses draw on linked administrative health data from the province of British Columbia for 1990 through 2000 for the population aged 50 and over. Joinpoint regression analyses and t-tests are used to detect and describe trends in the data. RESULTS: Generally speaking, non-avoidable hospitalizations constitute the vast majority of hospitalizations in a given year (i.e. around 95%) with AHRs constituting the remaining 5% of hospitalizations. Comparing rural areas and urban areas reveals that standardized rates of avoidable, non-avoidable and total hospitalizations are consistently higher in rural areas. Joinpoint regression results show significantly decreasing trends overall; lines are parallel in the case of avoidable hospitalizations, and lines are diverging for non-avoidable and total hospitalizations, with the gap between rural and urban areas being wider at the end of the time interval than at the beginning. CONCLUSION: These data suggest that access to effective primary care in rural communities remains problematic in BC given that rural areas did not make any gains in AHRs relative to urban areas under recent health sector restructuring initiatives. It remains important to continue to monitor the discrepancy between them as a reflection of inequity in service provision. In addition, it is important to consider alternative explanations for the observed trends paying particular attention to the needs of rural and urban populations and the factors influencing local service provision