Results of tan-hyperbolic pulse propagation in dispersion dominant regime as well as in the simultaneous presence of fiber loss, dispersion and self-phase modulation in single mode fiber are presented, both for initially un-chirped and chirped cases. Split-step Fourier model for nonlinear Schrodinger equation was used for this purpose. Results clearly show that in the presence of fiber nonlinearity, by increasing the steepness parameter, initially the un-chirped pulse first undergoes compression and then it goes on broadening with the propagated distance. Results also show that for higher value of steepness parameter, if the value of initial chirp goes on decreasing, peak power also increase showing the compression of the pulse and then it decreases with the propagated distance in dispersion dominant regime. The inclusion of self-phase modulation further enhances these results. These investigations provide a deeper insight for the fiber response to such type of optical pulses.

IMPORTANCE:The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain. OBJECTIVE:To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. DESIGN, SETTING, AND PARTICIPANTS:Analysis of individual-participant data available from 73 prospective studies involving 294,998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. MAIN OUTCOMES AND MEASURES:Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5% to <7.5%), and high (≥ 7.5%) risk. RESULTS:During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20,840 incident fatal and nonfatal CVD outcomes (13,237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA1c values and CVD risk. The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA1c was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (-0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels. CONCLUSIONS AND RELEVANCE:In a study of individuals without known CVD or diabetes, additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.

BACKGROUND:Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. METHODS:In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125,222 participants. We also compared the frequency of Asp358Ala in 51,441 patients with coronary heart disease and in 136,226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. FINDINGS:The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele ≥0·04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34·3% (95% CI 30·4-38·2) and of interleukin 6 by 14·6% (10·7-18·4), and mean concentration of C-reactive protein was reduced by 7·5% (5·9-9·1) and of fibrinogen by 1·0% (0·7-1·3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3·4% (1·8-5·0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. INTERPRETATION:Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease. FUNDING:British Heart Foundation; UK Medical Research Council; UK National Institute of Health Research, Cambridge Biomedical Research Centre; BUPA Foundation.

In this paper, an improved analysis for modulation instability, which results from interaction between optical wave and noise, is presented. It is shown that Nonlinear Schrodinger equation (NLSE), which governs this process, leads to the coupled wave equations that result to Riccati's differential equations. A completely analytical solution of Riccati's equation is obtained for small fiber length that results in efficient computation of the modulation instability effect.

CONTEXT:The value of assessing various emerging lipid-related markers for prediction of first cardiovascular events is debated. OBJECTIVE:To determine whether adding information on apolipoprotein B and apolipoprotein A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 to total cholesterol and high-density lipoprotein cholesterol (HDL-C) improves cardiovascular disease (CVD) risk prediction. DESIGN, SETTING, AND PARTICIPANTS:Individual records were available for 165,544 participants without baseline CVD in 37 prospective cohorts (calendar years of recruitment: 1968-2007) with up to 15,126 incident fatal or nonfatal CVD outcomes (10,132 CHD and 4994 stroke outcomes) during a median follow-up of 10.4 years (interquartile range, 7.6-14 years). MAIN OUTCOME MEASURES:Discrimination of CVD outcomes and reclassification of participants across predicted 10-year risk categories of low (<10%), intermediate (10%-<20%), and high (≥20%) risk. RESULTS:The addition of information on various lipid-related markers to total cholesterol, HDL-C, and other conventional risk factors yielded improvement in the model's discrimination: C-index change, 0.0006 (95% CI, 0.0002-0.0009) for the combination of apolipoprotein B and A-I; 0.0016 (95% CI, 0.0009-0.0023) for lipoprotein(a); and 0.0018 (95% CI, 0.0010-0.0026) for lipoprotein-associated phospholipase A2 mass. Net reclassification improvements were less than 1% with the addition of each of these markers to risk scores containing conventional risk factors. We estimated that for 100,000 adults aged 40 years or older, 15,436 would be initially classified at intermediate risk using conventional risk factors alone. Additional testing with a combination of apolipoprotein B and A-I would reclassify 1.1%; lipoprotein(a), 4.1%; and lipoprotein-associated phospholipase A2 mass, 2.7% of people to a 20% or higher predicted CVD risk category and, therefore, in need of statin treatment under Adult Treatment Panel III guidelines. CONCLUSION:In a study of individuals without known CVD, the addition of information on the combination of apolipoprotein B and A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 mass to risk scores containing total cholesterol and HDL-C led to slight improvement in CVD prediction.

BACKGROUNDThe extent to which diabetes mellitus or hyperglycemia is related to risk of death from cancer or other nonvascular conditions is uncertain.METHODSWe calculated hazard ratios for cause-specific death, according to baseline diabetes status or fasting glucose level, from individual-participant data on 123,205 deaths among 820,900 people in 97 prospective studies.RESULTSAfter adjustment for age, sex, smoking status, and body-mass index, hazard ratios among persons with diabetes as compared with persons without diabetes were as follows: 1.80 (95% confidence interval [CI], 1.71 to 1.90) for death from any cause, 1.25 (95% CI, 1.19 to 1.31) for death from cancer, 2.32 (95% CI, 2.11 to 2.56) for death from vascular causes, and 1.73 (95% CI, 1.62 to 1.85) for death from other causes. Diabetes (vs. no diabetes) was moderately associated with death from cancers of the liver, pancreas, ovary, colorectum, lung, bladder, and breast. Aside from cancer and vascular disease, diabetes (vs. no diabetes) was also associated with death from renal disease, liver disease, pneumonia and other infectious diseases, mental disorders, nonhepatic digestive diseases, external causes, intentional self-harm, nervous-system disorders, and chronic obstructive pulmonary disease. Hazard ratios were appreciably reduced after further adjustment for glycemia measures, but not after adjustment for systolic blood pressure, lipid levels, inflammation or renal markers. Fasting glucose levels exceeding 100 mg per deciliter (5.6 mmol per liter), but not levels of 70 to 100 mg per deciliter (3.9 to 5.6 mmol per liter), were associated with death. A 50-year-old with diabetes died, on average, 6 years earlier than a counterpart without diabetes, with about 40% of the difference in survival attributable to excess nonvascular deaths.CONCLUSIONSIn addition to vascular disease, diabetes is associated with substantial premature death from several cancers, infectious diseases, external causes, intentional self-harm, and degenerative disorders, independent of several major risk factors. (Funded by the British Heart Foundation and others.)

BACKGROUND:Guidelines differ about the value of assessment of adiposity measures for cardiovascular disease risk prediction when information is available for other risk factors. We studied the separate and combined associations of body-mass index (BMI), waist circumference, and waist-to-hip ratio with risk of first-onset cardiovascular disease. METHODS:We used individual records from 58 cohorts to calculate hazard ratios (HRs) per 1 SD higher baseline values (4.56 kg/m(2) higher BMI, 12.6 cm higher waist circumference, and 0.083 higher waist-to-hip ratio) and measures of risk discrimination and reclassification. Serial adiposity assessments were used to calculate regression dilution ratios. RESULTS:Individual records were available for 221,934 people in 17 countries (14,297 incident cardiovascular disease outcomes; 1.87 million person-years at risk). Serial adiposity assessments were made in up to 63,821 people (mean interval 5.7 years [SD 3.9]). In people with BMI of 20 kg/m(2) or higher, HRs for cardiovascular disease were 1.23 (95% CI 1.17-1.29) with BMI, 1.27 (1.20-1.33) with waist circumference, and 1.25 (1.19-1.31) with waist-to-hip ratio, after adjustment for age, sex, and smoking status. After further adjustment for baseline systolic blood pressure, history of diabetes, and total and HDL cholesterol, corresponding HRs were 1.07 (1.03-1.11) with BMI, 1.10 (1.05-1.14) with waist circumference, and 1.12 (1.08-1.15) with waist-to-hip ratio. Addition of information on BMI, waist circumference, or waist-to-hip ratio to a cardiovascular disease risk prediction model containing conventional risk factors did not importantly improve risk discrimination (C-index changes of -0.0001, -0.0001, and 0.0008, respectively), nor classification of participants to categories of predicted 10-year risk (net reclassification improvement -0.19%, -0.05%, and -0.05%, respectively). Findings were similar when adiposity measures were considered in combination. Reproducibility was greater for BMI (regression dilution ratio 0.95, 95% CI 0.93-0.97) than for waist circumference (0.86, 0.83-0.89) or waist-to-hip ratio (0.63, 0.57-0.70). INTERPRETATION:BMI, waist circumference, and waist-to-hip ratio, whether assessed singly or in combination, do not importantly improve cardiovascular disease risk prediction in people in developed countries when additional information is available for systolic blood pressure, history of diabetes, and lipids. FUNDING:British Heart Foundation and UK Medical Research Council.

Objective: Limited evidence suggests NT-proBNP improves prediction of coronary heart disease (CHD) events but further data are needed, especially in people without pre-existing CHD and in women.Methods: We measured NT-proBNP in serum from 162 women with incident CHD events and 1226 controls (60-79 years) in a case-control study nested within the prospective British Women's Heart and Health Study. All cases and controls were free from CHD at baseline. We related NT-proBNP to CHD event risk, and determined to what extent NT-proBNP enhanced CHD risk prediction beyond established risk factors.Results: The odds ratio for CHD per 1 standard deviation increase in loge NT-proBNP was 1.37 (95% CI: 1.13-1.68) in analyses adjusted for established CHD risk factors, social class, CRP and insulin. However, addition of loge NT-proBNP did not improve the discrimination of a prediction model including age, social class, smoking, physical activity, lipids, fasting glucose, waist: hip ratio, hypertension, statin and aspirin use, nor a standard Framingham risk score model; area under the receiver operator curve for the former model increased from 0.676 to 0.687 on inclusion of NT-proBNP (p = 0.3). Furthermore, adding NT-proBNP did not improve calibration of a prediction model containing established risk factors, nor did inclusion more appropriately re-classify participants in relation to their final outcome. Findings were similar (independent associations, but no prediction improvement) for fasting insulin and CRP.Conclusion: These results caution against use of NT-proBNP for CHD risk prediction in healthy women and suggest a need for larger studies in both genders to resolve outstanding uncertainties. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

BACKGROUND:Associations between circulating markers of dysglycaemia and coronary heart disease (CHD) risk in people without diabetes have not been reliably characterised. We report new data from a prospective study and a systematic review to help quantify these associations. METHODS AND FINDINGS:Fasting and post-load glucose levels were measured in 18,569 participants in the population-based Reykjavik study, yielding 4,664 incident CHD outcomes during 23.5 y of mean follow-up. In people with no known history of diabetes at the baseline survey, the hazard ratio (HR) for CHD, adjusted for several conventional risk factors, was 2.37 (95% CI 1.79-3.14) in individuals with fasting glucose > or = 7.0 mmol/l compared to those < 7 mmol/l. At fasting glucose values below 7 mmol/l, adjusted HRs were 0.95 (0.89-1.01) per 1 mmol/l higher fasting glucose and 1.03 (1.01-1.05) per 1 mmol/l higher post-load glucose. HRs for CHD risk were generally modest and nonsignificant across tenths of glucose values below 7 mmol/l. We did a meta-analysis of 26 additional relevant prospective studies identified in a systematic review of Western cohort studies that recorded fasting glucose, post-load glucose, or glycated haemoglobin (HbA(1c)) levels. In this combined analysis, in which participants with a self-reported history of diabetes and/or fasting blood glucose > or = 7 mmol/l at baseline were excluded, relative risks for CHD, adjusted for several conventional risk factors, were: 1.06 (1.00-1.12) per 1 mmol/l higher fasting glucose (23 cohorts, 10,808 cases, 255,171 participants); 1.05 (1.03-1.07) per 1 mmol/l higher post-load glucose (15 cohorts, 12,652 cases, 102,382 participants); and 1.20 (1.10-1.31) per 1% higher HbA(1c) (9 cohorts, 1639 cases, 49,099 participants). CONCLUSIONS:In the Reykjavik Study and a meta-analysis of other Western prospective studies, fasting and post-load glucose levels were modestly associated with CHD risk in people without diabetes. The meta-analysis suggested a somewhat stronger association between HbA(1c) levels and CHD risk.

Results of super-exponential pulse propagation in dispersion dominant regime of single mode fiber are presented, both for initially un-chirped and chirped cases. Split-step Fourier model for nonlinear Schrodinger equation was used for this purpose. Results clearly show that an initially un-chirped pulse first goes on compression and then broadens at higher rate if the steepness parameter goes on increasing. Results also show that for a fixed value of the steepness parameter, however larger than unity, the narrowing of the pulse experiences only for zero or negative values of initial chirp. These investigations provide a deeper insight for the fiber response to such type of optical pulses.

Background— Evidence is sparse about the genetic determinants of major lipids in Pakistanis. Methods and Results— Variants (n=45 000) across 2000 genes were assessed in 3200 Pakistanis and compared with 2450 Germans using the same gene array and similar lipid assays. We also did a meta-analysis of selected lipid-related variants in Europeans. Pakistani genetic architecture was distinct from that of several ethnic groups represented in international reference samples. Forty-one variants at 14 loci were significantly associated with levels of HDL-C, triglyceride, or LDL-C. The most significant lipid-related variants identified among Pakistanis corresponded to genes previously shown to be relevant to Europeans, such as CETP associated with HDL-C levels (rs711752; P <10 −13 ), APOA5/ZNF259 (rs651821; P <10 −13 ) and GCKR (rs1260326; P <10 −13 ) with triglyceride levels; and CELSR2 variants with LDL-C levels (rs646776; P <10 −9 ). For Pakistanis, these 41 variants explained 6.2%, 7.1%, and 0.9% of the variation in HDL-C, triglyceride, and LDL-C, respectively. Compared with Europeans, the allele frequency of rs662799 in APOA5 among Pakistanis was higher and its impact on triglyceride concentration was greater ( P -value for difference <10 −4 ). Conclusions— Several lipid-related genetic variants are common to Pakistanis and Europeans, though they explain only a modest proportion of population variation in lipid concentration. Allelic frequencies and effect sizes of lipid-related variants can differ between Pakistanis and Europeans.

BACKGROUND:Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality. METHODS:We assessed the -1131T>C (rs662799) promoter polymorphism of the apolipoprotein A5 (APOA5) gene in relation to triglyceride concentration, several other risk factors, and risk of coronary heart disease. We compared disease risk for genetically-raised triglyceride concentration (20,842 patients with coronary heart disease, 35,206 controls) with that recorded for equivalent differences in circulating triglyceride concentration in prospective studies (302 430 participants with no history of cardiovascular disease; 12,785 incident cases of coronary heart disease during 2.79 million person-years at risk). We analysed -1131T>C in 1795 people without a history of cardiovascular disease who had information about lipoprotein concentration and diameter obtained by nuclear magnetic resonance spectroscopy. FINDINGS:The minor allele frequency of -1131T>C was 8% (95% CI 7-9). -1131T>C was not significantly associated with several non-lipid risk factors or LDL cholesterol, and it was modestly associated with lower HDL cholesterol (mean difference per C allele 3.5% [95% CI 2.6-4.6]; 0.053 mmol/L [0.039-0.068]), lower apolipoprotein AI (1.3% [0.3-2.3]; 0.023 g/L [0.005-0.041]), and higher apolipoprotein B (3.2% [1.3-5.1]; 0.027 g/L [0.011-0.043]). By contrast, for every C allele inherited, mean triglyceride concentration was 16.0% (95% CI 12.9-18.7), or 0.25 mmol/L (0.20-0.29), higher (p=4.4x10(-24)). The odds ratio for coronary heart disease was 1.18 (95% CI 1.11-1.26; p=2.6x10(-7)) per C allele, which was concordant with the hazard ratio of 1.10 (95% CI 1.08-1.12) per 16% higher triglyceride concentration recorded in prospective studies. -1131T>C was significantly associated with higher VLDL particle concentration (mean difference per C allele 12.2 nmol/L [95% CI 7.7-16.7]; p=9.3x10(-8)) and smaller HDL particle size (0.14 nm [0.08-0.20]; p=7.0x10(-5)), factors that could mediate the effects of triglyceride. INTERPRETATION:These data are consistent with a causal association between triglyceride-mediated pathways and coronary heart disease. FUNDING:British Heart Foundation, UK Medical Research Council, Novartis.

In this paper, we propose and successfully show that power level of the optical pulse at the transmitter side can be increased and still having smaller pulse degradation, by introducing negative chirp in the input Gaussian pulse propagating through single mode fiber in anomalous dispersion regime. Split-step Fourier method based nonlinear Schrodinger equation model was used for these investigations. The results presented also show another interesting phenomenon that the effects of fiber dispersion and nonlinearity can be minimized by introducing a suitable value of input chirp in the launching pulse, and as a result the input pulse can be recovered in its original form at the output side at a certain propagated distance. A detailed analysis of un-chirped and chirped Gaussian pulses propagating through lossless/lossy single mode fiber both for normal and anomalous dispersion regimes, along with the effects of pre- and post-dispersion compensations is also provided.

OBJECTIVE:To quantify associations of chronic kidney disease stages with major cardiovascular disease and non-vascular mortality in the general adult population. DESIGN:Prospective population based cohort study. SETTING:Reykjavik, Iceland. PARTICIPANTS:16 958 people aged 33-81 years without manifest vascular disease and with available information on stage of chronic kidney disease (defined by both estimated glomerular filtration rate and urinary protein) at study entry. MAIN OUTCOME MEASURES:Hazard ratios for time to major coronary heart disease outcomes and mortality. RESULTS:1210 (7%) of participants had chronic kidney disease at entry. During a median follow-up of 24 years, 4010 coronary heart disease outcomes, 559 deaths from stroke, and 3875 deaths from non-vascular causes were recorded. Compared with the reference group (estimated glomerular filtration rate 75-89 ml/min/1.73 m(2) and no proteinuria), people with lower renal function within the normal range of glomerular filtration rate did not have significantly higher risk of coronary heart disease. By contrast, in 1210 (7%) participants with chronic kidney disease at entry, hazard ratios for coronary heart disease, adjusted for several conventional cardiovascular risk factors, were 1.55 (95% confidence interval 1.02 to 2.35) for stage 1, 1.72 (1.30 to 2.24) for stage 2, 1.39 (1.22 to 1.58) for stage 3a, 1.90 (1.22 to 2.96) for stage 3b, and 4.29 (1.78 to 10.32) for stage 4. Information on chronic kidney disease increased discrimination and reclassification indices for coronary heart disease when added to conventional risk factors (P<0.01). The incremental gain provided by chronic kidney disease was lower than that provided by diabetes or smoking (C index increases of 0.0015, 0.0024, and 0.0124 respectively). Hazard ratios with chronic kidney disease were 0.97 (0.82 to 1.15) for cancer mortality and 1.26 (1.07 to 1.50) for other non-vascular mortality. CONCLUSIONS:In people without manifest vascular disease, even the earliest stages of chronic kidney disease are associated with excess risk of subsequent coronary heart disease. Assessment of chronic kidney disease in addition to conventional risk factors modestly improves prediction of risk for coronary heart disease in this population. Further studies are needed to investigate associations between chronic kidney disease and non-vascular mortality from causes other than cancer.

In a collaborative analysis of 101 studies,1 the Triglyceride Coronary Disease Genetics Consortium and the Emerging Risk Factors Collaboration show the causal association between triglyceride-mediated pathways and coronary disease. We would like to point out that some confounding effects should be taken into account when judging the reliability of this association.

PURPOSE OF REVIEW:Despite over 50 years of research, the relevance of triglycerides to coronary heart disease risk remains uncertain. RECENT FINDINGS:Contrary to prevailing views, recent studies demonstrate that the long-term within-individual variability of triglyceride measurements is similar to that of other lipid fractions. Several prospective studies have reported on associations of circulating triglyceride levels with coronary heart disease risk, but it remains unclear whether observed associations are dependent on levels of conventional risk factors (especially other lipids) or are importantly modified under different circumstances (especially by fasting status). Ongoing large-scale studies should help clarify such outstanding uncertainties and assess whether measurement of triglyceride levels can better identify individuals at increased risk of coronary heart disease than measurement of conventional risk factors alone. Available interventions that lower levels of triglycerides are unable to judge causality as such interventions typically influence levels of several lipid fractions. Study of genetic variants that regulate triglyceride levels may provide an alternative approach to assess causality. SUMMARY:Although recent studies have progressed our understanding of triglycerides and coronary heart disease, several outstanding uncertainties remain unresolved. Ongoing studies should help clarify these, including whether measurement of triglyceride levels can help improve coronary heart disease risk assessment, and study of genetic variants may help better understand any causal role.

Cardiovascular disease is the leading cause of global mortality, with coronary heart disease (CHD) its major manifestation. Although inflammation, the body’s response to noxious stimuli, is implicated in several stages of CHD development, the relevance of circulating levels of markers of inflammation to CHD risk remains uncertain. This review summarizes available epidemiological evidence for four emerging inflammatory markers implicated in CHD (fibrinogen, C-reactive protein, lipoprotein-associated phospholipase A2 and interleukin-6); considers their likely utility in cardiovascular risk prediction; and outlines areas of outstanding uncertainty.

Results of cosh-Gaussian pulse propagation in dispersion dominant regime of single mode fiber are presented. Split-step Fourier model for nonlinear Schrodinger equation was used to obtain these results. The comparison of degradation of cosh-Gaussian pulse versus simple Gaussian pulse is provided. The results clearly show that cosh-Gaussian pulse experiences less broadening in comparison with a simple Gaussian pulse for the same propagated distance and other parameters. These studies are useful to have less pulse broadening in single mode fiber which is always desired in optical communications.