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    Significance of CD4 / CD8 ratio and C-reactive protein in monitoring cardiovascular risk in HIV positive patients during cART therapy

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    Uvod: HIV-infekcija se karakteriše progresivnim manjkom CD4+ T-ćelija zbog njihove smanjene sinteze, povećanog uništavanja i izrazite aktivacije i ekspanzije CD8+ T limfocita. CD4/CD8 odnos (količnik, engl. ratio) se sve više pojavljuje kao marker različitih ishoda kod HIV-inficiranih pojedinaca. S druge strane CRP je tradicionalno opisivan kao dobar marker akutne upale i danas je jedan od standardnih testova koji se koriste u svakodnevnoj kliničkoj praksi, za postavljanje dijagnoze i praćenje prognoze upale. Međutim, uloga CRP-a u različitim fiziološkim procesima, naročito kod perzistentne infekcije i imunske aktivacije nije do kraja jasna. Efikasnom i savremenom terapijom HIVa život ovakvih pacijenta je značajno produžen. Primarni cilj antiretrovirusne terapije (ART) je spriječiti HIV-povezane bolesti i smrtnost, a sekundarni cilj je da se smanji rizik od prijenosa HIV-a. Ovaj cilj se najbolje postiže pomoću efikasne cART, kojom se maksimalno inhibira HIV replikacija, tako da plazmatska HIV RNK (viremija) ostaje ispod nivoa kojeg je moguće detektovati pomoću komercijalno dostupnih testova. Cilj: Osnovni cilj ovog istraživanja je da se ispita kolika je moć CD4/CD8 odnosa i CRP-a da predvidi razvoj rizika kardiovaskularne bolesti (KVB) kod HIV pozitivnih pacijenata koji primaju cART terapiju. Materijal i metode: U retrospektivno-prospektivnoj kohortnoj studiji ponovljenih mjerenja bilo je uključeno 76 HIV pozitivnih ispitanika. Za određivanje udjela (procenta) CD4+ i CD8+ ćelija, iz periferne krvi pacijenata, korištena je metoda protočne citometrije. U ovoj studiji evaluirane su vrijednosti biohemijskih paremetara (CRP-a, lipidnog statusa), parametara krvne slike (eritrociti, hemogbin, hematokrit, trombociti), leukociti i leukocitarna formula te sedimentacija kao nespecifični parametri akutne upale, potom imunološki parametar CD4/CD8 odnos, antropometrijska mjerenja- ITM, te vrsta cART terapije. Za statističku analizu korišten je softver SPSS, odnosno parametrijski i neparamterijski testovi, Spirmanova (rho) korelacija, standardna regresiona analiza i ROC kriva. Rezultati: U istraživanje je uključeno 76 ispitanika, 67 (88,2 %) muškaraca i 9 (11,8 %) žena. Ispitanici su prosječne starosti 35,2±8,7 godina, najmlađi ispitanik imao je 18, a najstariji 57 godina. Standardnom regresionom analizom, ispitivan je uticaj nezavisnih prediktora (starosti, pola, navike pušenja, familijarne anameze za KVB, ITM, cART,5 sistolnog i dijastolnog pritiska, holesterola, triglicerda, HDL-a, ŠUK-a, CRP-a, CD4 i CD4/CD8) na zavisno promjenljivu rizik za KVB bazično i nakon 3, 6, 12, 18 i 24 mjeseca cART. Od 12. do 24. mjeseca osim standardnih rizikofaktora za predikciju razvoja KVB, CD4/CD8 odnos i CRP se javljaju kao značajni prediktori. Nakon 24 mjeseca cART, CRP se pokazao kao najbolji prediktor rizika za KVB (beta=0,224; p=0,026), veće vrijednosti ovog parametara utiču na veći rizik za KVB, potom CD4/CD8 odnos (beta=-0,200; p=0,025), s tim da veći odnos smanjuje vjerovatnoću za rizik KVB. Terapija (cART) u ovom regresionom modelu prvi put je nakon 24 mjeseca pokazala statistički značajan uticaj na rizik za KVB (beta=0,197; p=0,013). Ispitanici koji su u kombinovanoj terapiji imali PI, imaju veći rizik za KVB. Od 18. mjeseca cART CRP može biti marker srednjeg rizika za KVB, a nakon 24 mjeseca vrijednosti CRP-a od 5,31 mg/L ima najveću senzitivnost 78,3% i najveću specifičnost 86,8%, kao marker srednjeg u odnosu na niski rizik za KVB (p=0,0001; AUC=0,882). Od 12 mjeseca cART CD4/CD8 odnos može biti marker niskog rizika za KVB. Nakon 24 mjeseca terapije prosječna vrijednost CD4/CD8 odnosa od 0,53 ima najveću senzitivnost 66,0% i najveću specifičnost 73,9%, kako marker niskog u odnosu na srednji rizik za KVB (p=0,001; AUC =0,762). Zaključci: Količnik CD4/CD8 i CRP su se pokazali se kao značajni prediktori za rizik KVB, i kao markeri koji mogu razlikovati nizak/srednji rizik za KVB kod HIV pacijenata nakon 12 mjeseci cART.Introduction: HIV infection is characterized by a progressive deficiency of CD4+ T cells due to their reduced synthesis, increased destruction and marked activation and expansion of CD8+ T lymphocytes. The CD4/CD8 ratio is increasingly emerging as a marker of different outcomes in HIV-infected individuals. On the other hand, CRP has traditionally been described as a good marker of acute inflammation and is today one of the standard tests used in everyday clinical practice to diagnose and monitor inflammation prognosis. However, the role of CRP in various physiological processes, especially in persistent infections and immune activation, is not entirely clear. The primary goal of antiretroviral therapy (ART) is to prevent HIV-related diseases and mortality, and the secondary goal is to reduce the risk of HIV transmission. This goal is best achieved by using efficient combination ART (cART), which maximally inhibits HIV replication, so that plasma HIV RNA (viral load) remains below the level that can be detected by commercially available tests. Aim: The main objective of this study is to examine the power of the CD4/CD8 ratio and CRP in predicting the risk of development of cardiovascular disease (CVD) in HIV positive patients receiving cART therapy. Methods: In the retrospective-prospective cohort study of repeated measurements, 76 HIV positive subjects were included. The method of flow cytometry was used to determine the percentage of CD4+ and CD8+ cells in the peripheral blood of patients. In this study the values of biochemical parameters (CRP, lipid status), blood parameters (erythrocytes, hemoglobin, hematocrit, platelets), leukocytes, leukocyte formula, and sedimentation as non-specific parameters of acute inflammation were evaluated, followed by immunocompetent CD4/CD8 ratio, anthropometric measurements - ITM, and cART therapy type. For statistical analysis SPSS software was used, i.e. parametric and nonparametric tests, Spearman's (rho) correlation, standard regression analysis and ROC curve. Results: The study included 76 subjects, 67 (88.2%) males and 9 (11.8%) women. The average age of subjects was 35.2 ± 8.7 years; the youngest subject was 18 and the oldest 57 years old. By standard regression analysis, the influence of independent predictors (age, gender, smoking habits, familial anamnesis for CVD, ITM, cART, systolic and diastolic7 pressure, cholesterol, triglycerides, HDL, blood sugar, CRP, CD4 and CD4/CD8 ratio) on the dependent variable risk of CVD, baseline and after 3, 6, 12, 18 and 24 months of cART was examined. From 12 to 24 months apart from the standard risk factors for predicting the development of CVD, CD4/CD8 ratio and CRP appear as significant predictors. After 24 months of cART, CRP proved to be the best risk predictor of CVD (beta = 0.224; p = 0.026), higher values of this parameter affect higher risk for CVD, then CD4/CD8 ratio (beta -0.200, p = 0.025), with a higher ratio decreasing the likelihood of CVD risk. Therapy (cART) in this regression model showed the first time after 24 months a statistically significant impact on CVD risk (beta = 0.197; p = 0.013). Subjects who had PI in combination therapy had a higher risk for CVD. From 18 months of cART CRP may be a medium risk marker for CVD, and after 24 months the CRP value of 5.31 mg/L has the highest sensitivity of 78.3% and the highest specificity of 86.8%, as a marker of medium compared to low risk for CVD (p = 0.0001; AUC = 0.882). After 12 months of cART CD4/CD8 ratio can be a low risk marker for CVD. After 24 months of therapy, the average CD4/CD8 ratio of 0.53 had the highest sensitivity 66.0% and the highest specificity was 73.9%, as the marker of low compared to medium risk for CVD (p = 0.001, AUC = 0.762). Conclusion: CD4/CD8 ratio and CRP counts have been shown to be significant CVD risk predictors, and as markers that may differentiate low and intermediate risk for CVD in HIV patients after 12 months of cART

    Significance of CD4 / CD8 ratio and C-reactive protein in monitoring cardiovascular risk in HIV positive patients during cART therapy

    No full text
    Uvod: HIV-infekcija se karakteriše progresivnim manjkom CD4+ T-ćelija zbog njihove smanjene sinteze, povećanog uništavanja i izrazite aktivacije i ekspanzije CD8+ T limfocita. CD4/CD8 odnos (količnik, engl. ratio) se sve više pojavljuje kao marker različitih ishoda kod HIV-inficiranih pojedinaca. S druge strane CRP je tradicionalno opisivan kao dobar marker akutne upale i danas je jedan od standardnih testova koji se koriste u svakodnevnoj kliničkoj praksi, za postavljanje dijagnoze i praćenje prognoze upale. Međutim, uloga CRP-a u različitim fiziološkim procesima, naročito kod perzistentne infekcije i imunske aktivacije nije do kraja jasna. Efikasnom i savremenom terapijom HIVa život ovakvih pacijenta je značajno produžen. Primarni cilj antiretrovirusne terapije (ART) je spriječiti HIV-povezane bolesti i smrtnost, a sekundarni cilj je da se smanji rizik od prijenosa HIV-a. Ovaj cilj se najbolje postiže pomoću efikasne cART, kojom se maksimalno inhibira HIV replikacija, tako da plazmatska HIV RNK (viremija) ostaje ispod nivoa kojeg je moguće detektovati pomoću komercijalno dostupnih testova. Cilj: Osnovni cilj ovog istraživanja je da se ispita kolika je moć CD4/CD8 odnosa i CRP-a da predvidi razvoj rizika kardiovaskularne bolesti (KVB) kod HIV pozitivnih pacijenata koji primaju cART terapiju. Materijal i metode: U retrospektivno-prospektivnoj kohortnoj studiji ponovljenih mjerenja bilo je uključeno 76 HIV pozitivnih ispitanika. Za određivanje udjela (procenta) CD4+ i CD8+ ćelija, iz periferne krvi pacijenata, korištena je metoda protočne citometrije. U ovoj studiji evaluirane su vrijednosti biohemijskih paremetara (CRP-a, lipidnog statusa), parametara krvne slike (eritrociti, hemogbin, hematokrit, trombociti), leukociti i leukocitarna formula te sedimentacija kao nespecifični parametri akutne upale, potom imunološki parametar CD4/CD8 odnos, antropometrijska mjerenja- ITM, te vrsta cART terapije. Za statističku analizu korišten je softver SPSS, odnosno parametrijski i neparamterijski testovi, Spirmanova (rho) korelacija, standardna regresiona analiza i ROC kriva. Rezultati: U istraživanje je uključeno 76 ispitanika, 67 (88,2 %) muškaraca i 9 (11,8 %) žena. Ispitanici su prosječne starosti 35,2±8,7 godina, najmlađi ispitanik imao je 18, a najstariji 57 godina. Standardnom regresionom analizom, ispitivan je uticaj nezavisnih prediktora (starosti, pola, navike pušenja, familijarne anameze za KVB, ITM, cART,5 sistolnog i dijastolnog pritiska, holesterola, triglicerda, HDL-a, ŠUK-a, CRP-a, CD4 i CD4/CD8) na zavisno promjenljivu rizik za KVB bazično i nakon 3, 6, 12, 18 i 24 mjeseca cART. Od 12. do 24. mjeseca osim standardnih rizikofaktora za predikciju razvoja KVB, CD4/CD8 odnos i CRP se javljaju kao značajni prediktori. Nakon 24 mjeseca cART, CRP se pokazao kao najbolji prediktor rizika za KVB (beta=0,224; p=0,026), veće vrijednosti ovog parametara utiču na veći rizik za KVB, potom CD4/CD8 odnos (beta=-0,200; p=0,025), s tim da veći odnos smanjuje vjerovatnoću za rizik KVB. Terapija (cART) u ovom regresionom modelu prvi put je nakon 24 mjeseca pokazala statistički značajan uticaj na rizik za KVB (beta=0,197; p=0,013). Ispitanici koji su u kombinovanoj terapiji imali PI, imaju veći rizik za KVB. Od 18. mjeseca cART CRP može biti marker srednjeg rizika za KVB, a nakon 24 mjeseca vrijednosti CRP-a od 5,31 mg/L ima najveću senzitivnost 78,3% i najveću specifičnost 86,8%, kao marker srednjeg u odnosu na niski rizik za KVB (p=0,0001; AUC=0,882). Od 12 mjeseca cART CD4/CD8 odnos može biti marker niskog rizika za KVB. Nakon 24 mjeseca terapije prosječna vrijednost CD4/CD8 odnosa od 0,53 ima najveću senzitivnost 66,0% i najveću specifičnost 73,9%, kako marker niskog u odnosu na srednji rizik za KVB (p=0,001; AUC =0,762). Zaključci: Količnik CD4/CD8 i CRP su se pokazali se kao značajni prediktori za rizik KVB, i kao markeri koji mogu razlikovati nizak/srednji rizik za KVB kod HIV pacijenata nakon 12 mjeseci cART.Introduction: HIV infection is characterized by a progressive deficiency of CD4+ T cells due to their reduced synthesis, increased destruction and marked activation and expansion of CD8+ T lymphocytes. The CD4/CD8 ratio is increasingly emerging as a marker of different outcomes in HIV-infected individuals. On the other hand, CRP has traditionally been described as a good marker of acute inflammation and is today one of the standard tests used in everyday clinical practice to diagnose and monitor inflammation prognosis. However, the role of CRP in various physiological processes, especially in persistent infections and immune activation, is not entirely clear. The primary goal of antiretroviral therapy (ART) is to prevent HIV-related diseases and mortality, and the secondary goal is to reduce the risk of HIV transmission. This goal is best achieved by using efficient combination ART (cART), which maximally inhibits HIV replication, so that plasma HIV RNA (viral load) remains below the level that can be detected by commercially available tests. Aim: The main objective of this study is to examine the power of the CD4/CD8 ratio and CRP in predicting the risk of development of cardiovascular disease (CVD) in HIV positive patients receiving cART therapy. Methods: In the retrospective-prospective cohort study of repeated measurements, 76 HIV positive subjects were included. The method of flow cytometry was used to determine the percentage of CD4+ and CD8+ cells in the peripheral blood of patients. In this study the values of biochemical parameters (CRP, lipid status), blood parameters (erythrocytes, hemoglobin, hematocrit, platelets), leukocytes, leukocyte formula, and sedimentation as non-specific parameters of acute inflammation were evaluated, followed by immunocompetent CD4/CD8 ratio, anthropometric measurements - ITM, and cART therapy type. For statistical analysis SPSS software was used, i.e. parametric and nonparametric tests, Spearman's (rho) correlation, standard regression analysis and ROC curve. Results: The study included 76 subjects, 67 (88.2%) males and 9 (11.8%) women. The average age of subjects was 35.2 ± 8.7 years; the youngest subject was 18 and the oldest 57 years old. By standard regression analysis, the influence of independent predictors (age, gender, smoking habits, familial anamnesis for CVD, ITM, cART, systolic and diastolic7 pressure, cholesterol, triglycerides, HDL, blood sugar, CRP, CD4 and CD4/CD8 ratio) on the dependent variable risk of CVD, baseline and after 3, 6, 12, 18 and 24 months of cART was examined. From 12 to 24 months apart from the standard risk factors for predicting the development of CVD, CD4/CD8 ratio and CRP appear as significant predictors. After 24 months of cART, CRP proved to be the best risk predictor of CVD (beta = 0.224; p = 0.026), higher values of this parameter affect higher risk for CVD, then CD4/CD8 ratio (beta -0.200, p = 0.025), with a higher ratio decreasing the likelihood of CVD risk. Therapy (cART) in this regression model showed the first time after 24 months a statistically significant impact on CVD risk (beta = 0.197; p = 0.013). Subjects who had PI in combination therapy had a higher risk for CVD. From 18 months of cART CRP may be a medium risk marker for CVD, and after 24 months the CRP value of 5.31 mg/L has the highest sensitivity of 78.3% and the highest specificity of 86.8%, as a marker of medium compared to low risk for CVD (p = 0.0001; AUC = 0.882). After 12 months of cART CD4/CD8 ratio can be a low risk marker for CVD. After 24 months of therapy, the average CD4/CD8 ratio of 0.53 had the highest sensitivity 66.0% and the highest specificity was 73.9%, as the marker of low compared to medium risk for CVD (p = 0.001, AUC = 0.762). Conclusion: CD4/CD8 ratio and CRP counts have been shown to be significant CVD risk predictors, and as markers that may differentiate low and intermediate risk for CVD in HIV patients after 12 months of cART

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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