Omega-3 fatty acids, cardiovascular disease and stability of atherosclerotic plaques

Long-chain n-3 polyunsaturated fatty acids are found in oily fish and in fish oils and similar preparations. Substantial evidence from epidemiological and case-control studies indicates that consumption of fish, oily fish and long-chain n-3 fatty acids reduces risk of cardiovascular mortality. Secondary prevention studies using long-chain n-3 fatty acids in patients post-myocardial infarction have shown a reduction in total and cardiovascular mortality with an especially potent effect on sudden death. Long-chain n-3 fatty acids have been shown to beneficially modify a range of cardiovascular risk factors, which may result in primary cardiovascular prevention. However, reduced non-fatal and fatal events and a reduction in sudden death probably involve other mechanisms. Reduced thrombosis following long-chain n-3 fatty acids may play a role. A decrease in arrhythmias is a favoured mechanism of action of long-chain n-3 fatty acids and is supported by cell culture and animal studies. However human trials using implantable cardiac defibrillators have produced inconsistent findings and a recent meta-analysis does not support this mechanism of action. An alternative mechanism of action may be stabilisation of atherosclerotic plaques by long-chain n-3 fatty acids. This is suggested by one published human study which showed that incorporation of long-chain n-3 fatty acids into plaques collected at carotid endarterectomy resulted in fewer macrophages in the plaque and a morphology indicative of increased stability. These findings are supported from observations in an animal model and suggest that the primary effect of long-chain n-3 fatty acids might be on macrophages within the plaque.

Simultaneous observations of reconnection pulses at Cluster and their effects on the cusp aurora seen at Chinese Yellow River Station

While the Cluster spacecraft were located near the high-latitude magnetopause, between 10:10 and 10:40 UT on 16 January 2004, three typical flux transfer event (FTE) signatures were observed. During this interval, simultaneous and conjugated all-sky camera measurements, recorded at Yellow River Station, Svalbard, are available at 630.0 and 557.7nm that show poleward-moving auroral forms (PMAFs), consistent with magnetic reconnection at dayside magnetopause. Simultaneous FTEs seen at the magnetopause mainly move northward, but having duskward (eastward) and tailward velocity components, roughly consistent with the observed direction of motion of the PMAFs in all-sky images. Between the PMAFs meridional keograms, extracted from the all-sky images, show intervals of lower intensity aurora which migrate equatorward just before the PMAFs intensify. This is strong evidence for an equatorward eroding and poleward moving open-closed boundary (OCB) associated with a variable magnetopause reconnection rate under variable IMF conditions. From the durations of the PMAFs we infer that the evolution time of FTEs is 5-11 minutes from its origin on magnetopause to its addition to the polar cap.

Decadal-scale rainfall variability in Ethiopia recorded in an annually laminated, Holocene-age, stalagmite

An annually laminated, uranium-series dated, Holocene stalagmite from southeast Ethiopia has been analysed for growth rate and δ13C and ��18O variations at annual to biennial resolution, in order to provide the first long duration proxy record of decadal-scale rainfall variability in this climatically sensitive region. Our study site (10��N) is climatically influenced by both summer (June���August) and spring (March—May) rainfall caused by the annual movement of the Inter-Tropical Convergence Zone (ITCZ) and modulated by large-scale anomalies in the atmospheric circulation and in ocean temperatures. Here we show that stalagmite growth, episodic throughout the last 7800 years, demonstrates decadal-scale (8—25 yr) variability in both growth rate and δ 18O. A hydrological model was employed and indicates that this decadal variability is due to variations in the relative amounts of rainfall in the two rain seasons. Our record, unique in its combination of length (a total of ~1000 years), annual chronology and high resolution δ18O, shows for the first time that such decadal-scale variability in rainfall in this region has occurred through the Holocene, which implies persistent decadal-scale variability for the large-scale atmospheric and oceanic driving factors.

Initial results from Phase 2 of the international urban energy balance model comparison

Urban land surface schemes have been developed to model the distinct features of the urban surface and the associated energy exchange processes. These models have been developed for a range of purposes and make different assumptions related to the inclusion and representation of the relevant processes. Here, the first results of Phase 2 from an international comparison project to evaluate 32 urban land surface schemes are presented. This is the first large-scale systematic evaluation of these models. In four stages, participants were given increasingly detailed information about an urban site for which urban fluxes were directly observed. At each stage, each group returned their models' calculated surface energy balance fluxes. Wide variations are evident in the performance of the models for individual fluxes. No individual model performs best for all fluxes. Providing additional information about the surface generally results in better performance. However, there is clear evidence that poor choice of parameter values can cause a large drop in performance for models that otherwise perform well. As many models do not perform well across all fluxes, there is need for caution in their application, and users should be aware of the implications for applications and decision making.

Peptides generated ex vivo from serum proteins by tumor-specific exopeptidases are not useful biomarkers in ovarian cancer

BACKGROUND: The serum peptidome may be a valuable source of diagnostic cancer biomarkers. Previous mass spectrometry (MS) studies have suggested that groups of related peptides discriminatory for different cancer types are generated ex vivo from abundant serum proteins by tumor-specific exopeptidases. We tested 2 complementary serum profiling strategies to see if similar peptides could be found that discriminate ovarian cancer from benign cases and healthy controls. METHODS: We subjected identically collected and processed serum samples from healthy volunteers and patients to automated polypeptide extraction on octadecylsilane-coated magnetic beads and separately on ZipTips before MALDI-TOF MS profiling at 2 centers. The 2 platforms were compared and case control profiling data analyzed to find altered MS peak intensities. We tested models built from training datasets for both methods for their ability to classify a blinded test set. RESULTS: Both profiling platforms had CVs of approximately 15% and could be applied for high-throughput analysis of clinical samples. The 2 methods generated overlapping peptide profiles, with some differences in peak intensity in different mass regions. In cross-validation, models from training data gave diagnostic accuracies up to 87% for discriminating malignant ovarian cancer from healthy controls and up to 81% for discriminating malignant from benign samples. Diagnostic accuracies up to 71% (malignant vs healthy) and up to 65% (malignant vs benign) were obtained when the models were validated on the blinded test set. CONCLUSIONS: For ovarian cancer, altered MALDI-TOF MS peptide profiles alone cannot be used for accurate diagnoses.

Incorporation of cis-9,trans-11 or trans-10,cis-12 conjugated linoleic acid into plasma and cellular lipids in healthy men

This study investigated the incorporation of cis-9,trans-11 conjugated linoleic acid (c9,t11 CLA) and trans-10,cis-12-CLA (t10,c12 CLA) into plasma and peripheral blood mononuclear cell (PBMC) lipids when consumed as supplements highly enriched in these isomers. Healthy men (n = 49, age 31 +/- 8 years) consumed one, two, and four capsules containing similar to600 mg of either c9,t11 CIA or t10,c12 CLA per capsule for sequential 8 week periods followed by a 6 week washout before consuming the alternative isomer. Both isomers were incorporated in a dosedependent manner into plasma phosphatidylcholine (PC) (c9,t11 CLA r = 0.779, t10,c12 CLA r = 0.738; P < 0.0001) and cholesteryl ester (CE) (c9,t11 CLA r = 0.706, t10,c12 CLA r = 0.788; P < 0.0001). Only t10,c12 CLA was enriched in plasma nonesterified fatty acids. Both c9,t11 CIA and t10,c12 CLA were incorporated linearly into PBMC total lipids (r = 0.285 and r = 0.273, respectively; P < 0.0005). The highest concentrations of c9,t11 CLA and t10,c12 CLA in PBMC lipids were 3- to 4-fold lower than those in plasma PC and CE. These data suggest that the level of intake is a major determinant of plasma and PBMC CLA content, although PBMCs appear to incorporate both CLA isomers less readily.

Fragmentation or creative diversity? Options in the provision of land management advisory services

Rural land managers need access to sound advice and information to respond to pressures from environmental regulations, declining farm incomes, changing patterns in international trade and new institutional arrangements within the domestic food chain. Governments have cut back their provision of advisory services but need more than ever to influence land managers' decisions to achieve a growing array of policy objectives: The paper develops a conceptual framework for analysing advisory services and concludes, through a review of sixteen case studies, that the needs of both governments and land managers can be met by a diverse mixture of private and public sector provision. (C) 2003 Elsevier Ltd. All rights reserved.

Influence of socio-economic and cultural factors in rice varietal diversity management on-farm in Nepal

A questionnaire survey of 408 households explored the role of socio-economic and cultural factors in rice (Oryza sativa L.) varietal diversity management on-farm in two contrasting eco-sites in Nepal. Multiple regression outputs suggest that number of parcels of land, livestock number, number of rice ecosystems, agro-ecology (altitude), and use of chemical fertilizer have a significant positive influence on landrace diversity on-farm, while membership in farmers' groups linked to extension services has significant but negative influence on landrace diversity. Factors with significant positive influence on diversity of modern varieties on-farm were number of parcels of land and of rice ecosystems, access to irrigation, membership in farmers' groups, and use of insecticide. Within communities, resource-endowed households maintain significantly higher varietal diversity on-farm than resource-poor households and play a significant role in conserving landraces that are vulnerable to genetic erosion and those with socio-cultural and market-preferred traits. Resource-poor households also contribute to local diversity conservation but at lower richness and area coverage levels than resource-endowed households. Households where a female had assumed the role of head of household due to death or migrant work of her husband had less diversity due to lower labor availability. Landraces with socio-cultural and market-preferred traits are few in number but have potential to be conserved on-farm.

Splanchnic metabolism of dairy cows during the transition from late gestation through early lactation

Blood flow and net nutrient fluxes for portal-drained viscera (PDV) and liver ( total splanchnic tissues) were measured at 19 and 9 d prepartum and at 11, 21, 33, and 83 d in milk ( DIM) in 5 multiparous Holstein-Friesian cows. Cows were fed a grass silage-based gestation ration initially and a corn silage-based lactation ration peripartum and postpartum. Meals were fed at 8-h intervals and hourly (n = 8) measures of splanchnic metabolism were started before ( 0730 h and 0830 h) feeding at 0830 h. Dry matter intakes (DMI) at 19 and 9 d prepartum were not different. Metabolism changes measured from 19 to 9 d prepartum were lower arterial insulin and acetate, higher arterial nonesterified fatty acids and increased net liver removal of glycerol. After calving, PDV and liver blood flow and oxygen consumption more than doubled as DMI and milk yield increased, but 85 and 93% of the respective increases in PDV and liver blood flow at 83 DIM had occurred by 11 DIM. Therefore, factors additional to DMI must also contribute to increased blood flow in early lactation. Most postpartum changes in net PDV and liver metabolism could be attributed to increases in DMI and digestion or increased milk yield and tissue energy loss. Glucose release was increasingly greater than calculated requirements as DIM increased, presumably as tissue energy balance increased. Potential contributions of lactate, alanine, and glycerol to liver glucose synthesis were greatest at 11 DIM but decreased by 83 DIM. Excluding alanine, there was no evidence of an increased contribution of amino acids to liver glucose synthesis is required in early lactation. Increased net liver removal of propionate (69%), lactate (20%), alanine (8%), and glycerol (4%) can account for increased liver glucose release in transition cows from 9 d before to 11 d after calving.

Inter-laboratory variation of in vitro cumulative gas production profiles of feeds using manual and automated methods

A study was conducted to estimate variation among laboratories and between manual and automated techniques of measuring pressure on the resulting gas production profiles (GPP). Eight feeds (molassed sugarbeet feed, grass silage, maize silage, soyabean hulls, maize gluten feed, whole crop wheat silage, wheat, glucose) were milled to pass a I mm screen and sent to three laboratories (ADAS Nutritional Sciences Research Unit, UK; Institute of Grassland and Environmental Research (IGER), UK; Wageningen University, The Netherlands). Each laboratory measured GPP over 144 h using standardised procedures with manual pressure transducers (MPT) and automated pressure systems (APS). The APS at ADAS used a pressure transducer and bottles in a shaking water bath, while the APS at Wageningen and IGER used a pressure sensor and bottles held in a stationary rack. Apparent dry matter degradability (ADDM) was estimated at the end of the incubation. GPP were fitted to a modified Michaelis-Menten model assuming a single phase of gas production, and GPP were described in terms of the asymptotic volume of gas produced (A), the time to half A (B), the time of maximum gas production rate (t(RM) (gas)) and maximum gas production rate (R-M (gas)). There were effects (P<0.001) of substrate on all parameters. However, MPT produced more (P<0.001) gas, but with longer (P<0.001) B and t(RM gas) (P<0.05) and lower (P<0.001) R-M gas compared to APS. There was no difference between apparatus in ADDM estimates. Interactions occurred between substrate and apparatus, substrate and laboratory, and laboratory and apparatus. However, when mean values for MPT were regressed from the individual laboratories, relationships were good (i.e., adjusted R-2 = 0.827 or higher). Good relationships were also observed with APS, although they were weaker than for MPT (i.e., adjusted R-2 = 0.723 or higher). The relationships between mean MPT and mean APS data were also good (i.e., adjusted R 2 = 0. 844 or higher). Data suggest that, although laboratory and method of measuring pressure are sources of variation in GPP estimation, it should be possible using appropriate mathematical models to standardise data among laboratories so that data from one laboratory could be extrapolated to others. This would allow development of a database of GPP data from many diverse feeds. (c) 2005 Published by Elsevier B.V.

An adaptive approach to implementing bivariate group sequential clinical trial designs

In clinical trials, situations often arise where more than one response from each patient is of interest; and it is required that any decision to stop the study be based upon some or all of these measures simultaneously. Theory for the design of sequential experiments with simultaneous bivariate responses is described by Jennison and Turnbull (Jennison, C., Turnbull, B. W. (1993). Group sequential tests for bivariate response: interim analyses of clinical trials with both efficacy and safety endpoints. Biometrics 49:741-752) and Cook and Farewell (Cook, R. J., Farewell, V. T. (1994). Guidelines for monitoring efficacy and toxicity responses in clinical trials. Biometrics 50:1146-1152) in the context of one efficacy and one safety response. These expositions are in terms of normally distributed data with known covariance. The methods proposed require specification of the correlation, �� between test statistics monitored as part of the sequential test. It can be difficult to quantify ρ and previous authors have suggested simply taking the lowest plausible value, as this will guarantee power. This paper begins with an illustration of the effect that inappropriate specification of ρ can have on the preservation of trial error rates. It is shown that both the type I error and the power can be adversely affected. As a possible solution to this problem, formulas are provided for the calculation of correlation from data collected as part of the trial. An adaptive approach is proposed and evaluated that makes use of these formulas and an example is provided to illustrate the method. Attention is restricted to the bivariate case for ease of computation, although the formulas derived are applicable in the general multivariate case.