39 research outputs found
Factors Associated with D-Dimer Levels in HIV-Infected Individuals
No full textBackground: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood.
Methods: In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4(+) count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol.
Results: Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels.
Conclusions: D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels
Severity of cardiovascular disease outcomes among patients with hiv is related to markers of inflammation and coagulation
No full textBackground: In the general population, raised levels of inflammatory markers are stronger predictors of fatal than nonfatal cardiovascular disease (CVD) events. People with HIV have elevated levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and D-dimer; HIV-induced activation of inflammatory and coagulation pathways may be responsible for their greater risk of CVD. Whether the enhanced inflammation and coagulation associated with HIV is associated with more fatal CVD events has not been investigated. Methods and Results: Biomarkers were measured at baseline for 9764 patients with HIV and no history of CVD. Of these patients, we focus on the 288 that experienced either a fatal (n=74) or nonfatal (n=214) CVD event over a median of 5 years. Odds ratios (ORs) (fatal versus nonfatal CVD) (95% confidence intervals [CIs]) associated with a doubling of IL-6, D-dimer, hsCRP, and a 1-unit increase in an IL-6 and D-dimer score, measured a median of 2.6 years before the event, were 1.39 (1.07 to 1.79), 1.40 (1.10 to 1.78), 1.09 (0.93 to 1.28), and 1.51 (1.15 to 1.97), respectively. Of the 214 patients with nonfatal CVD, 23 died during follow-up. Hazard ratios (95% CI) for all-cause mortality were 1.72 (1.28 to 2.31), 1.73 (1.27 to 2.36), 1.44 (1.15 to 1.80), and 1.88 (1.39 to 2.55), respectively, for IL-6, D-dimer, hsCRP, and the IL-6 and D-dimer score. Conclusions: Higher IL-6 and D-dimer levels reflecting enhanced inflammation and coagulation associated with HIV are associated with a greater risk of fatal CVD and a greater risk of death after a nonfatal CVD event. Clinical Trial Registration: URL: http://www.clinicaltrial.gov Unique identifier: SMART: NCT00027352, ESPRIT: NCT00004978, SILCAAT: NCT00013611
Severity of cardiovascular disease outcomes among patients with HIV is related to markers of inflammation and coagulation
No full textBACKGROUND: In the general population, raised levels of inflammatory markers are stronger predictors of fatal than nonfatal cardiovascular disease (CVD) events. People with HIV have elevated levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and D-dimer; HIV-induced activation of inflammatory and coagulation pathways may be responsible for their greater risk of CVD. Whether the enhanced inflammation and coagulation associated with HIV is associated with more fatal CVD events has not been investigated. METHODS AND RESULTS: Biomarkers were measured at baseline for 9764 patients with HIV and no history of CVD. Of these patients, we focus on the 288 that experienced either a fatal (n=74) or nonfatal (n=214) CVD event over a median of 5 years. Odds ratios (ORs) (fatal versus nonfatal CVD) (95% confidence intervals [CIs]) associated with a doubling of IL-6, D-dimer, hsCRP, and a 1-unit increase in an IL-6 and D-dimer score, measured a median of 2.6 years before the event, were 1.39 (1.07 to 1.79), 1.40 (1.10 to 1.78), 1.09 (0.93 to 1.28), and 1.51 (1.15 to 1.97), respectively. Of the 214 patients with nonfatal CVD, 23 died during follow-up. Hazard ratios (95% CI) for all-cause mortality were 1.72 (1.28 to 2.31), 1.73 (1.27 to 2.36), 1.44 (1.15 to 1.80), and 1.88 (1.39 to 2.55), respectively, for IL-6, D-dimer, hsCRP, and the IL-6 and D-dimer score. CONCLUSIONS: Higher IL-6 and D-dimer levels reflecting enhanced inflammation and coagulation associated with HIV are associated with a greater risk of fatal CVD and a greater risk of death after a nonfatal CVD event. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrial.gov Unique identifier: SMART: NCT00027352, ESPRIT: NCT00004978, SILCAAT: NCT00013611
Globalization, Social Movements, and the Construction of Europe: The Example of the European Parliament Elections in France, CES Working Paper, no. 74, August 2000
No full textThough social scientists have lately devoted themselves to the study of globalization (Waters 1995; Hirst and Thompson 1999), most of these studies have concentrated on its economic and social consequences. Globalization is often seen as a fundamentally unjust process that causes confusion and destroys more than it creates. In many areas, the substantive implications of globalization are left untouched. In this paper, I examine the link between regional integration in Western Europe and the transformation of domestic politics through the example of the European Parliament elections. I argue that globalization through European integration is having a significant impact on French domestic politics. More precisely, the elections to the European Parliament, a supranational political institution, have contributed to the political mobilization of traditionally voiceless groups such as the unemployed and to the introduction into public discussion of new issues tied to Europe, transforming political culture and the relationship between national politics and multinational bargaining (Keohane and Hoffmann 1990, 295). Not only has European political integration provided marginal groups in France with an access to national politics through European Parliament elections, it has also supplied the government and the presidency with new resources, connecting them to trans-European circles and networks that are developing their own political culture. The success of neoliberal economic doctrines in the European Union may have in part to do with these networks. National ministers spend half their time wrestling with European affairs in the Council of Ministers of the European Union and in transnational party structures, developing a common culture and outlook on politics and economics. The main ingredients for this Weltanschauung are well known: electoral cycles should not interfere with economic policy and unemployment figures should not have priority over other monetary indices in the evaluation of economic and political success
Risk Factors for Lobar and Non-Lobar Intracerebral Hemorrhage in Patients with Vascular Disease.
No full textLobar and non-lobar non-traumatic intracerebral hemorrhage (ICH) are presumably caused by different types of small vessel diseases. The aim of this study was to assess risk factors for ICH according to location.In two large prospective studies, SMART (n = 9088) and ESPRIT (n = 2625), including patients with manifest cardiovascular, cerebrovascular or peripheral artery disease or with vascular risk factors, we investigated potential risk factors for ICH during follow-up according to lobar or non-lobar location by Cox proportional hazards analyses.During 65,156 patient years of follow up 19 patients had lobar ICH (incidence rate 29, 95% CI 19-42 per 100,000 person-years) and 24 non-lobar ICH (incidence rate 37, 95% CI 26-51 per 100,000 person-years). Age significantly increased the risk of lobar ICH (HR per 10 years increase 1.90; 95% CI 1.17-3.10) in the multivariable analysis, but not of non-lobar hemorrhage. Anticoagulant medication (HR 3.49; 95% CI 1.20-10.2) and male sex (HR 3.79; 95% CI 1.13-12.8) increased the risk of non-lobar but not lobar ICH.This study shows an elevated risk of future ICH in patients with manifestations of, or risk factors for, cardiovascular, cerebrovascular or peripheral artery disease. Our data suggest that risk factors for ICH vary according to location, supporting the hypothesis of a differential pathophysiology of lobar and non-lobar ICH
Risk of all-cause mortality associated with nonfatal AIDS and serious non-AIDS events among adults infected with HIV.
No full textOBJECTIVES: Among patients with HIV, the risk of death associated with different AIDS events has been quantified, but the risk of death associated with non-AIDS events has not been examined. We compared the risk of all-cause mortality following AIDS versus serious non-AIDS (SNA) events in the Strategies for Management of Antiretroviral Therapy (SMART) study and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT). DESIGN: Data from 9583 HIV-infected participants, 5472 with a CD4 cell count more than 350 cells/microl enrolled in SMART and 4111 with a CD4 cell count 300 cells/microl or more enrolled in ESPRIT, were analyzed. METHODS: Cumulative mortality 6 months after AIDS and SNA events (cardiovascular, renal, hepatic disease, and malignancies) was estimated using the Kaplan-Meier method. Cox models were used to estimate hazard ratios associated with AIDS and SNA events on the risk of death overall and by treatment group within study. RESULTS: AIDS and SNA events occurred in 286 and 435 participants with 47 (16%) and 115 (26%) subsequent deaths, respectively. Six-month cumulative mortality was 4.7% [95% confidence interval (CI) 2.8-8.0] after experiencing an AIDS event and 13.4% (95% CI 10.5-17.0) after experiencing an SNA event. The adjusted hazard ratio for all-cause mortality for those who experienced AIDS versus those who did not was 4.9 (95% CI 3.6-6.8). The corresponding hazard ratio for SNA was 11.4 (95% CI 9.0-14.5) (P < 0.001 for difference in hazard ratios). Findings were similar for both treatment groups in SMART and both treatment groups in ESPRIT. CONCLUSION: Among HIV-infected persons with higher CD4 cell counts, SNA events occur more frequently and are associated with a greater risk of death than AIDS events. Future research should be aimed at comparing strategies to reduce morbidity and mortality associated with SNA events for HIV-infected persons
Interleukin-6, high sensitivity C-reactive protein, and the development of type 2 diabetes among HIV-positive patients taking antiretroviral therapy
No full textBackground: HIV infection is associated with increased levels of inflammatory markers. Inflammation is hypothesized to play a role in the development of type 2 diabetes. Data addressing this issue among HIV-positive participants are limited.Methods: A cohort of 3695 participants without diabetes, taking antiretroviral therapy and with an average CD4(+) count of 523 cells/mm(3), were followed for an average of 4.6 years. Diabetes risk associated with baseline levels of high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) was assessed using Cox proportional hazards regression models. Analyses considered baseline levels of factors associated with diabetes risk and HIV-related measures.Results: One hundred thirty-seven patients developed diabetes requiring drug treatment during follow-up (8.18 per 1000 person-years). Median levels of IL-6 and hsCRP were significantly higher among those who developed diabetes compared with those who did not: 3.45 versus 2.50 pg/mL for IL-6 and 4.91 versus 3.29 mu g/mL for hsCRP (P < 0.001). Adjusted hazard ratios associated with a doubling of IL-6 and hsCRP were 1.29 (95% confidence interval: 1.08 to 1.55; P = 0.005) and 1.22 (95% confidence interval: 1.10 to 1.36; P < 0.001), respectively. Body mass index (P < 0.001), age (P = 0.013), coinfection with hepatitis B or C (P = 0.03), nonsmoking status (P = 0.034), and use of lipid-lowering treatment (P = 0.008) were also associated with an increased risk of diabetes.Conclusions: These findings indicate that low-grade systemic inflammation is an underlying factor in the pathogenesis of diabetes
Esprit. European Strategic Programme for Research and Development in Information Technology. Progress and results 1991/92. EUR 14451 EN
No full textCirculating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study
No full textIntroduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection
A practice based learning environment for engineering students: Acquiring competencies for working on advanced manufacturing engineering
No full textThis thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.In this thesis the author describes the design and operation of a learning environment aimed at imparting technical, technological and managerial knowledge, developing understanding of the underlying issues and enhancing team work skills for an advanced technology future. He offers an analysis of learning, education and training and compares group work with individual tasks, presents a major case study and illustrates the features which distinguish the approach from role play, simulation and experiential learning. When staff at Brunel University were faced with the problem of teaching Computer Integrated Manufacturing (CIM) to engineering students on thin sandwich type undergraduate degree programmes the writer suggested the use of an approach he would later describe as 'practice based learning' or 'real life simulation'. The fourth year course in CIM is designed as a double option for the complementary undergraduate courses, Brunel Manufacturing Engineering (BME) and Special Engineering Programmes (SEP). It is an extension of the Manufacturing Design and Practice course in years one to three of the BME course and of the Design strand on SEP, both of which restrict students' work to the use of individual machine tools and stand alone computing facilities. A wide range of teaching methods is used on the CIM course, including lectures by course staff, presentations by experts and, as the major element, a large group project involving all the students on the course, organised in a management matrix, coordinated by the students and supported by the staff acting as experts. The students also undertake assignment work alongside the technical tasks, to focus their thinking and to improve written communication skills. While the course described cannot replace more than a small proportion of the more conventional lecture, laboratory and tutorial teaching on an engineering programme, it provides a setting where students can experiment and learn about their own strengths and weaknesses in a realistic situation and in the context of teamwork. It also offers a space where they can make quite serious mistakes without direct consequences to their careers. The experience of seven years leads the author to believe that advanced manufacturing technologies and the associated management techniques should be taught in a project based environment with clear and real targets and realistic constraints, offering students challenges to which they can only rise through close and creative team work. The management of task execution must be left largely in the students' own hands. A high level of "consultant" type support is essential though, allied to an assessment scheme which promises and ensures fair treatment of the individual. The different parts of the thesis will be relevant to readers depending on their interest and background. Chapter 1 sets the scene and outlines the approach taken. Following this broad outline of the scope of the dissertation the author places Computer Integrated Manufacturing in a wider context in chapter 2, by providing an introduction to the underlying issues of computer integration and human factors. He puts forward a case for new approaches to the education and training of engineers and managers who will be working in Computer Integrated Manufacturing and Advanced Manufacturing Environments in general. Chapter 3 is devoted to the management of projects while chapter 4 is used to question the role of the engineer. Chapters 5 and 6 provide an introduction to theories of knowledge, teaching, learning and motivation. Chapters 7 and 8 are devoted to particular aspects of engineering education, while chapter 9 reviews the approach used at Brunel University. The topical issues of competence and its relevance to engineering education is discussed in chapter 10, leading into chapters 11 and 12 which deal with aspects of the CIM course. Chapters 13 and 14 are devoted to case-studies and particular tools. The key question of assessment of a practice oriented and team based course is addressed in chapter 15, followed by an evaluation of the CIM process and its application to engineering education of a full time nature which is included in chapters 17 and 18.Funding was obtained from The General Electric Company Prize 1993: Manufacturing Systems Engineering
