Implications of crop model ensemble size and composition for estimates of adaptation effects and agreement of recommendations.

Climate change is expected to severely affect cropping systems and food production in many parts of the world unless local adaptation can ameliorate these impacts. Ensembles of crop simulation models can be useful tools for assessing if proposed adaptation options are capable of achieving target yields, whilst also quantifying the share of uncertainty in the simulated crop impact resulting from the crop models themselves. Although some studies have analysed the influence of ensemble size on model outcomes, the effect of ensemble composition has not yet been properly appraised. Moreover, results and derived recommendations typically rely on averaged ensemble simulation results without accounting sufficiently for the spread of model outcomes. Therefore, we developed an Ensemble Outcome Agreement (EOA) index, which analyses the effect of changes in composition and size of a multi-model ensemble (MME) to evaluate the level of agreement between MME outcomes with respect to a given hypothesis (e.g. that adaptation measures result in positive crop responses). We analysed the recommendations of a previous study performed with an ensemble of 17 crop models and testing 54 adaptation options for rainfed winter wheat (Triticum aestivum L.) at Lleida (NE Spain) under perturbed conditions of temperature, precipitation and atmospheric CO2 concentration. Our results confirmed that most adaptations recommended in the previous study have a positive effect. However, we also showed that some options did not remain recommendable in specific conditions if different ensembles were considered. Using EOA, we were able to identify the adaptation options for which there is high confidence in their effectiveness at enhancing yields, even under severe climate perturbations. These include substituting spring wheat for winter wheat combined with earlier sowing dates and standard or longer duration cultivars, or introducing supplementary irrigation, the latter increasing EOA values in all cases. There is low confidence in recovering yields to baseline levels, although this target could be attained for some adaptation options under moderate climate perturbations. Recommendations derived from such robust results may provide crucial information for stakeholders seeking to implement adaptation measures.

Use of crop simulation modelling to aid ideotype design of future cereal cultivars.

A major challenge of the 21st century is to achieve food supply security under a changing climate and roughly a doubling in food demand by 2050 compared to present, the majority of which needs to be met by the cereals wheat, rice, maize, and barley. Future harvests are expected to be especially threatened through increased frequency and severity of extreme events, such as heat waves and drought, that pose particular challenges to plant breeders and crop scientists. Process-based crop models developed for simulating interactions between genotype, environment, and management are widely applied to assess impacts of environmental change on crop yield potentials, phenology, water use, etc. During the last decades, crop simulation has become important for supporting plant breeding, in particular in designing ideotypes, i.e. 'model plants', for different crops and cultivation environments. In this review we (i) examine the main limitations of crop simulation modelling for supporting ideotype breeding, (ii) describe developments in cultivar traits in response to climate variations, and (iii) present examples of how crop simulation has supported evaluation and design of cereal cultivars for future conditions. An early success story for rice demonstrates the potential of crop simulation modelling for ideotype breeding. Combining conventional crop simulation with new breeding methods and genetic modelling holds promise to accelerate delivery of future cereal cultivars for different environments. Robustness of model-aided ideotype design can further be enhanced through continued improvements of simulation models to better capture effects of extremes and the use of multi-model ensembles.

The role of plasma phospholipid transfer protein (PLTP) in HDL remodeling in acute-phase patients.

During reverse cholesterol transport plasma phospholipid transfer protein (PLTP) converts high density lipoprotein(3) (HDL(3)) into two new subpopulations, HDL(2)-like particles and pre-beta-HDL. The acute-phase response is accompanied with dramatic changes in lipid metabolism including alterations in HDL concentration, composition, and thereby its function as a substrate for HDL remodeling proteins in circulation. To evaluate how acute-phase HDL (AP-HDL) functions in PLTP-mediated HDL conversion, we collected plasma samples from patients with severe acute-phase response (n=17), and from healthy controls (n=30). Subsequently, total HDL (1.063

Infections, inflammation, and the risk of coronary heart disease.

BACKGROUND: The role of infections and inflammation in the pathophysiology of coronary heart disease is emerging. We studied the independent and joint effects of these 2 components on coronary risk. METHODS AND RESULTS: We measured baseline levels of C-reactive protein (CRP) and antibodies to adenovirus, enterovirus, cytomegalovirus, and herpes simplex virus as well as to Chlamydia pneumoniae (Cpn) and Helicobacter pylori in 241 subjects who suffered either myocardial infarction or coronary death during the 8.5-year trial in the Helsinki Heart Study, a coronary primary prevention trial. The 241 controls in this nested case-control study were subjects who completed the study without coronary events. Antibody levels to herpes simplex type I (HSV-1) and to Cpn were higher in cases than in controls, whereas the distributions of antibodies to other infectious agents were similar. Mean CRP was higher in cases (4.4 versus 2.0 mg/L; P<0.001), and high CRP increased the risks associated with smoking and with high antimicrobial antibody levels. The odds ratios in subjects with high antibody and high CRP levels were 25.4 (95% CI 2.9-220.3) for HSV-1 and 5.4 (95% CI 2.4-12.4) for Cpn compared with subjects with low antibody levels and low CRP. High antibody levels to either HSV-1 or to Cpn increased the risk independently of the other, and their joint effect was close to additive. CONCLUSIONS: Two chronic infections, HSV-1 and Cpn, increase the risk of coronary heart disease. The effect is emphasized in subjects with ongoing inflammation, denoted by increased CRP levels.

Prediction of myocardial infarction in dyslipidemic men by elevated levels of immunoglobulin classes A, E, and G, but not M.

BACKGROUND: Immune mechanisms have been suggested to play an important role in the development of coronary atherosclerosis and its thrombotic complications. We evaluated the predictive value of the levels of various serum immunoglobulin classes in middle-aged men at increased risk of myocardial infarction. METHODS: Using nested case-control design and logistic regression analysis, we estimated the association between serum immunoglobulins and the risk of coronary end points (nonfatal or fatal myocardial infarction or sudden cardiac death) in dyslipidemic men (levels of non-high-density lipoprotein cholesterol >5.2 mmol/L [>201 mg/dL]) participating in the Helsinki Heart Study. The cases consisted of 135 subjects in whom a coronary end point occurred during the 5-year observation period of the study, and the controls were 135 subjects who did not suffer coronary end points during this period. Levels of IgA, IgE, IgG, and IgM were determined in serum samples collected at study entry. RESULTS: Levels of IgA, IgE, and IgG, but not IgM, were significantly higher in cases than in controls. After adjustment for other risk factors, such as age, smoking, and blood pressure, the risk of coronary disease showed a significant relation to the levels of IgA, IgE, and IgG. The risk in the highest quartile of each distribution as compared with the lowest quartile was 2.2-fold for IgA (95% confidence interval, 1.0-4.5), 2.8-fold for IgE (1.3-5.9), and 2.8-fold for IgG (1.3-5.9). Hypertriglyceridemia and a low level of high-density lipoprotein cholesterol were associated with increased risk of a coronary end point only if the levels of IgA, IgE, or IgG were also elevated. CONCLUSION: Elevated levels of IgA, IgE, and IgG are associated with myocardial infarction and cardiac death in men with dyslipidemia. The present data suggest that, for dyslipidemia to cause coronary atherothrombosis, an immune response reflected by elevated levels of these immunoglobulin classes is an important determinant.

Antibody against oxidized low-density lipoprotein predicting myocardial infarction.

BACKGROUND: Oxidation of low-density lipoprotein is believed to be an important step in the pathogenesis of atherosclerosis. The purpose of the present study was to determine whether antibody against oxidized low-density lipoprotein, reported to be associated with the progression of carotid atherosclerosis, is predictive of cardiac death and nonfatal myocardial infarction. METHODS: Serum samples from 135 cases and their controls, drawn at entry from middle-aged dyslipidemic men participating in the Helsinki Heart Study, a 5-year coronary primary prevention trial with gemfibrozil, were tested for immunoglobulin G class antibodies against oxidized low-density lipoprotein by enzyme-linked immunosorbent assay. RESULTS: The mean antibody level, expressed in optical density units, was significantly higher in cases than in controls (0.412 vs 0.356, P = .002). After adjustment for age, smoking, blood pressure, and high-density lipoprotein cholesterol level, there was a 2.5-fold increased risk (95% confidence interval, 1.3 to 4.9) of a cardiac end point in the highest tertile of antibody level vs the lowest tertile (P = .005 for trend). CONCLUSIONS: Elevated levels of antibodies against oxidized low-density lipoprotein were predictive of myocardial infarction. The effect was independent of low-density lipoprotein cholesterol levels, and the joint effect was additive. Elevated antibody levels modified the effects of classic coronary risk factors.

Proteomic identification of allergenic seed proteins, napin and cruciferin, from cold-pressed rapeseed oils.

In Finland and France atopic children commonly react to seeds of oilseed rape and turnip rape in skin prick tests (SPT) and open food challenges. These seeds are not as such in dietary use and therefore the routes of sensitization are unknown. Possible allergens were extracted from commercial cold-pressed and refined rapeseed oils and identified by gel-based tandem nanoflow liquid chromatography mass spectrometry (LC-MS/MS). Napin (a 2S albumin), earlier identified as a major allergen in the seeds of oilseed rape and turnip rape, and cruciferin (an 11S globulin), a new potential seed allergen, were detected in cold-pressed oils, but not in refined oils. Pooled sera from five children sensitized or allergic to oilseed rape and turnip rape seeds reacted to these proteins from cold-pressed oil preparations and individual sera from five children reacted to these proteins extracted from the seeds when examined with IgE immunoblotting. Hence cold-pressed rapeseed oil might be one possible route of sensitization for these allergens.

The association of c-reactive protein, serum amyloid a and fibrinogen with prevalent coronary heart disease--baseline findings of the PAIS project.

Recent data suggest that infections, inflammation and the immune system are involved in the process of atherosclerosis. The aim of the present study was to analyze the association of coronary heart disease (CHD) with three inflammation markers, C-reactive protein (CRP), serum amyloid-A (SAA) and plasma fibrinogen. The cross-sectional study included 1400 men aged 45-74 years, who participated in a cardiovascular risk factor survey in Finland in 1997. Participants with prevalent CHD had markedly higher CRP, SAA and fibrinogen levels than participants without CHD. In logistic regression models, the age, smoking, serum cholesterol and systolic blood pressure adjusted odds ratios (2nd, 3rd and 4th quartile as compared with the 1st quartile) of CHD increased gradually with increasing quartile of CRP (1.90, 2.27, 2.64), SAA (1.68, 1.83, 2.41), and fibrinogen (1.60, 1.95, 2.14). The associations weakened somewhat after further adjustment for indicators of obesity, particularly waist hip-ratio. CRP, SAA and fibrinogen levels were markedly lower among CHD patients using cholesterol-lowering medication as compared to non-users. In conclusion, CRP, SAA and fibrinogen, which are markers of inflammation, were positively and significantly associated with prevalent CHD. Central obesity needs to be considered as a confounding factor in the observed associations. These findings support the hypothesis that cholesterol-lowering drugs have an anti-inflammatory effect.

Relation of inflammation to vascular function in patients with coronary heart disease.

Endothelium plays a pivotal role in the regulation of vascular relaxation. Inflammation may in turn induce endothelial dysfunction and thus increase the risk of atherothrombosis. We investigated 31 men with angiographically verified coronary heart disease, aged 57. 7+/-5.3 years, in regard to endothelium-dependent, acetylcholine-induced, and to endothelium-independent, sodium nitroprusside-induced vasodilatation in the forearm vasculature by strain-gauge plethysmography. Logistic regression analysis served to determine the relation between forearm vascular function and the inflammatory factors measured, concentration of C-reactive protein, subtypes of peripheral blood T-lymphocytes, and other factors potentially affecting endothelial function (lipoprotein and glucose levels). Concentration of C-reactive protein was an independent determinant of endothelium-dependent vascular function (P<0.001 for low dose acetylcholine, P=0.01 for high dose acetylcholine). Other determinants of endothelium-dependent vascular dysfunction were CD8-lymphocytes expressing ICAM-1 (P=0.001), antibodies to oxidized low-density lipoprotein (P<0.001), and body weight (P=0.007). The present data showed an association between inflammatory risk factors linked to atherothrombosis and endothelial dysfunction in coronary heart disease patients. It is possible that endothelial dysfunction in coronary heart disease patients is related to the chronic inflammation or infection coexisting with atherosclerosis.

IgG rheumatoid factor. Detection by enzyme immunoassay in rheumatoid arthritis and normal subjects.

IgG rheumatoid factors were demonstrated by enzyme immunoassay using, as antigen, goat antibodies to human serum albumin in the form of immune complexes. Elevated levels of IgG rheumatoid factor were noted in the majority of patients with seropositive rheumatoid arthritis but also relatively often in normal blood donors. Reactivity of IgG rheumatoid factor was in most instances inhibitable by IgG from various species, including man. Exceptionally, restricted specificity towards IgG from bovidae, was recognized.

Circulating immune complexes after kidney transplantation.

Sera from patients who had received renal allografts were studied for the presence of circulating immune complexes by using platelet aggregation technique combined with density gradient centrifugation. A simple and highly reproducible modification of the platelet aggregation technique, employing the use of relatively small amounts of blood from pretested donors as the source for platelets, is described. Immune complexes were detected in post-transplantation sera from 3 out of 16 patients. The development of a persistent immune complex state as a consequence of grafting was concluded in one patient.

Antibodies to prothrombin imply a risk of myocardial infarction in middle-aged men.

Antiphospholipid antibodies in patients with "antiphospholipid syndrome" may be directed at least in part against plasma phospholipid-binding proteins, such as beta 2-glycoprotein I or prothrombin, which are involved in the control of thrombosis and haemostasis. IgG-class antibodies against prothrombin and beta 2-glycoprotein I were measured by enzyme-linked immunoassay in initially healthy middle-aged dyslipidaemic men (non-high-density lipoprotein > 5.2 mml/l). Serum samples had been drawn at entry to a 5-year coronary primary-prevention trial with gemfibrozil from 106 subjects who experienced either a non-fatal myocardial infarction or cardiac death during the follow-up and from 106 subjects without coronary episodes, matched for treatment group (gemfibrozil/placebo) and geographical area. The antiprothrombin antibody level, as expressed in optical density units, was significantly higher in patients than in controls (0.26 +/- 0.17 versus 0.22 +/- 0.09; p < 0.02). A high level of antiprothrombin antibodies (highest tertile of distribution) predicted a 2.5-fold increase in the risk (95% confidence interval 1.2-5.3) of myocardial infarction or cardiac death. The distribution of IgG-class antibodies against beta 2-glycoprotein I did not differ significantly between cases and controls. The joint effect of antiprothrombin antibodies and other factors associated with hypercoagulative state: triglyceride level, lipoprotein(a) and smoking, was multiplicative for the risk. Antiprothrombin antibodies are a new immunological predictor of myocardial infarction and the effect of these antibodies may be mediated by hypercoagulative mechanisms.

High antibody levels to prothrombin imply a risk of deep venous thrombosis and pulmonary embolism in middle-aged men--a nested case-control study.

Antibodies against phospholipid-binding plasma proteins, such as beta2-glycoprotein I (beta2-GPI) and prothrombin, are associated with thromboembolic events in patients with systemic lupus erythematosus and also in subjects with no evident underlying diseases. We wanted to examine whether increased levels of antibodies to negatively-charged phospholipids (cardiolipin), to phospholipid-binding plasma proteins beta2-GPI and prothrombin and to oxidised low-density lipoprotein (LDL) were associated with risk of deep venous thrombosis or pulmonary embolism in subjects with no previous thrombosis. The antibodies were measured in stored serum samples from 265 cases of deep venous thrombosis of the lower extremity or pulmonary embolism occurring during a median follow-up of about 7 years and from 265 individually matched controls. The study subjects were middle-aged men participating in a cancer prevention trial of alpha-tocopherol and beta-carotene and the cases of thromboembolic events were identified from nationwide Hospital Discharge Register. The risk for thrombotic events was significantly increased only in relation to antiprothrombin antibodies. As adjusted for body mass index, number of daily cigarettes and history of chronic bronchitis, myocardial infarction and heart failure at baseline, the odds ratio per one unit of antibody was 6.56 (95% confidence interval 1.73-25.0). The seven highest individual optical density-unit values of antiprothrombin antibodies were all confined to subjects with thromboembolic episodes. In conclusion, the present nested case-control study showed that high autoantibody levels against prothrombin implied a risk of deep venous thrombosis and pulmonary embolism and could be involved in the development of the thrombotic processes.

IgM class autoantibodies in human cord serum.

It has previously been shown that human neonatal B lymphocytes in vitro can synthesize autoantibodies which typically are of IgM class, polyreactive and of low affinity and thought to represent natural autoantibodies. We screened 1034 cord serum specimens to find sera with elevated IgM levels; 98 such sera were further examined by an enzyme-linked immunosorbent assay (ELISA) to determine whether antibodies against a panel of autoantigens could be found. We detected low levels of IgM class antibodies against cardiolipin, pyruvate dehydrogenase, single-stranded DNA, thyroglobulin and Fc fragments of IgG as rheumatoid factors. The IgM concentration correlated with autoantibody levels. The specificity of the autoantibody assays was confirmed by inhibition tests. We conclude that several types of autoantibodies can be found in some sera of newborns and that increased IgM concentration of some neonates may reflect a polyclonal antibody response.

Improved immunoturbidimetric method for rheumatoid factor testing.

The performance of two immunoturbidimetric modifications for rheumatoid factor (RF) testing, which differ with respect to the means of complement inactivation (heat treatment and inactivation with polyvinyl sulphonate), were compared in serum samples from 87 patients with rheumatoid arthritis (RA) and from 403 healthy subjects. IgM-rheumatoid factor titres were also measured with an enzyme linked immunosorbent assay (ELISA). Both immunoturbidimetric tests gave positive reactions (rheumatoid factor > or = 20 IU/ml) in 74 out of the 87 (85%) RA sera. In cases with high RF concentrations the results after chemical inactivation tended to be slightly higher compared with heat inactivation. In healthy subjects rheumatoid factor was detected in 19/403 (4.7%) sera using heat inactivation and in 22/403 (5.5%) sera with chemical inactivation of complement. Interrun coefficient of variation in the chemical inactivation assay was 4.4%; with the heat inactivation method it was 8.1%. In the ELISA, a marginally better correlation was noted in the results obtained using chemical inactivation. Inactivation of complement by means of polyvinyl sulphonate offers the advantage of easier test performance and better reproducibility, and the results may reflect more accurately true rheumatoid factor concentrations.

Antibodies to oxidized low-density lipoprotein and to cardiolipin in nonpregnant and pregnant women with habitual abortion.

OBJECTIVE: To determine the occurrence of antibodies to oxidized low-density lipoprotein (LDL) in women with a history of habitual abortion before and during pregnancy. DESIGN: Immunoglobulin G class antibodies to malondialdehyde modified LDL were determined by a solid-phase ELISA in 42 habitual aborters before pregnancy, in 39 patients during pregnancy, and in 23 comparable nonpregnant and 22 pregnant control women without a history of abortion. In addition, we assessed the presence of anticardiolipin antibodies by ELISA in the same sera. SETTING: Departments I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki, Helsinki, Finland. RESULTS: Early pregnancy was accompanied by a decrease in the median levels of antibodies to oxidized LDL both in habitual aborters and in the control series. Only one patient exhibited a raised level of antibodies to oxidized LDL before pregnancy but, during pregnancy, nine patients (23%) had elevated levels of antibodies to oxidized LDL, similar to women with a favorable outcome of pregnancy (6/27, 22%) and in women whose current pregnancy also ended in abortion (3/12, 25%). Cardiolipin binding antibodies were detected in three habitual aborters before pregnancy (7%) and in nine women during pregnancy (23%), with a tendency to be more frequent in patients with miscarrying pregnancies than in those with continuing pregnancies (4/12, 33% and 5/27, 19%). Antibodies to oxidized LDL and cardiolipin were simultaneously present in three habitual aborters with continuing pregnancies. CONCLUSIONS: Increased levels of antibodies to oxidized LDL and cardiolipin may be associated with habitual abortion.

Antibodies to beta 2-glycoprotein I and prothrombin in habitual abortion.

OBJECTIVE: To determine the occurrence of antibodies to beta 2-glycoprotein I (beta 2-GP-I) and prothrombin in women with histories of habitual abortions when pregnant and nonpregnant. DESIGN: Antibodies to beta 2-GP-I and prothrombin were measured by ELISA using irradiated polystyrene plates in 43 women with habitual abortions and 22 healthy controls. SETTING: Departments I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki. PATIENT(S): Twenty-two women of the habitual abortion patients had never delivered (primary aborters) and 21 had delivered at least one living child before miscarriage (secondary aborters). INTERVENTION(S): Venous blood samples were collected before and during pregnancy. MAIN OUTCOME MEASURE(S): Immunoglobulin G class antibodies to beta 2-GP-I and prothrombin. RESULT(S): The secondary aborters showed higher levels of antibodies to prothrombin than the primary aborters when both pregnant and nonpregnant and also showed higher levels of antiprothrombin antibodies than the controls when pregnant. No such differences were found in levels of antibodies to beta 2-GP-I. The habitual abortion patients showed a tendency toward higher levels of these autoantibodies when pregnant than when nonpregnant. Gestational diabetes was more common among the antibody-positive habitual abortion patients than among the antibody-negative patients. CONCLUSION(S): Increased levels of antiprothrombin antibodies were associated with secondary abortions. Elevated levels of antibodies to beta 2-GP-I and prothrombin often were found in habitual abortion patients with gestational diabetes.

Association of markers of systemic inflammation, C reactive protein, serum amyloid A, and fibrinogen, with socioeconomic status.

STUDY OBJECTIVE: Systemic inflammation may play an important part in the development of cardiovascular disease. It has also been shown that socioeconomic status predicts cardiovascular events independently of established risk factors. The aim of this study was to analyse the association of three sensitive markers of systemic inflammation: C reactive protein (CRP), serum amyloid A protein (SAA), and fibrinogen, with socioeconomic status. DESIGN: Cross sectional study. SETTING: Eastern and southern Finland. PARTICIPANTS: 1503 men aged 45 to 74 years who participated in a cardiovascular risk factor survey in 1997. Based on the levels of education and family income, the men were classified to three socioeconomic groups. MAIN RESULTS: Mean concentrations of CRP (p for the trend <0.001), SAA (p for the trend 0.018), and fibrinogen (p for the trend <0.001) decreased substantially with increasing socioeconomic status. The trends in CRP and fibrinogen remained statistically significant after adjustment for smoking, waist to hip ratio, and prevalent longstanding diseases, and a non-significant trend was found for SAA (p for the trend 0.118). The inverse association between inflammation markers and socioeconomic status was particularly strong among the men below 60 years of age. CONCLUSIONS: Systemic inflammation is a potential mediator, especially among young and middle aged men, for the association between socioeconomic status and cardiovascular disease.

IgG-rheumatoid factor in a population of elderly males: relationship to IgM-rheumatoid factor and rheumatoid arthritis.

The occurrence of IgG-rheumatoid factor (RF) reacting with rabbit IgG was studied in the sera of 1,105 elderly males from rural areas of Finland. Elevated levels of IgG-RF were found in 12 sera, 11 of which contained also IgM-RF, as measured by conventional agglutination tests and/or by enzyme-linked immunosorbent assay. Subjects with rheumatoid arthritis and those with "false" positive RF reactions did not differ from each other with respect to the occurrence of IgG-RF.

False-positive seroreactions for syphilis as a harbinger of disease revisited.

A cohort of 59 initially healthy subjects with chronic false-positive seroreactions for syphilis was followed for 3 to 19 years (mean 13 years) by data linkage to computerized population registry and to national hospital discharge registry using a unique personal identification number. One subject had moved abroad, but all others were known to be alive at the end of the follow-up period. Four subjects developed systemic lupus erythematosus and two developed rheumatoid arthritis. One subject was admitted to hospital because of protracted substernal pain, but a myocardial infarction could not be verified. This case corresponds to the expected number of cardiovascular events in the cohort. A chronic false positive seroreaction for syphilis was calculated to represent a hundred-fold risk for the development of systemic lupus, but such seroreactions did not seem to predict an excess of cardiovascular diseases.