Neutropenia as an adverse event following vaccination : results from randomized clinical trials in healthy adults and systematic review

Background : In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance. Methodology : We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context. Principal Findings : Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations. Conclusions : It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events

Exploration of the use of Bayesian modeling of gradients for censored spatiotemporal data from the Deepwater Horizon oil spill

This paper develops a hierarchical framework for identifying spatiotemporal patterns in data with a high degree of censoring using the gradient process. To do this, we impute censored values using a sampling-based inverse CDF method within our Markov chain Monte Carlo algorithm, thereby avoiding burdensome integration and facilitating efficient estimation of other model parameters. We illustrate use of our methodology using a simulated data example, and uncover the danger of simply substituting a space- and time-constant function of the level of detection for all missing values. We then fit our model to area measurement data of volatile organic compounds (VOC) air concentrations collected on vessels supporting the response and clean-up efforts of the Deepwater Horizon oil release that occurred starting April 20, 2010. These data contained a high percentage of observations below the detectable limits of the measuring instrument. Despite this, we were still able to make some interesting discoveries, including elevated levels of VOC near the site of the oil well on June 26th. Using the results from this preliminary analysis, we hope to inform future research on the Deepwater Horizon study, including the use of gradient methods for assigning workers to exposure categories

FOXP3 Expression Is Upregulated in CD4+T Cells in Progressive HIV-1 Infection and Is a Marker of Disease Severity

Understanding the role of different classes of T cells during HIV infection is critical to determining which responses correlate with protective immunity. To date, it is unclear whether alterations in regulatory T cell (Treg) function are contributory to progression of HIV infection.FOXP3 expression was measured by both qRT-PCR and by flow cytometry in HIV-infected individuals and uninfected controls together with expression of CD25, GITR and CTLA-4. Cultured peripheral blood mononuclear cells were stimulated with anti-CD3 and cell proliferation was assessed by CFSE dilution.HIV infected individuals had significantly higher frequencies of CD4(+)FOXP3(+) T cells (median of 8.11%; range 1.33%-26.27%) than healthy controls (median 3.72%; range 1.3-7.5%; P = 0.002), despite having lower absolute counts of CD4(+)FOXP3(+) T cells. There was a significant positive correlation between the frequency of CD4(+)FOXP3(+) T cells and viral load (rho = 0.593 P = 0.003) and a significant negative correlation with CD4 count (rho = -0.423 P = 0.044). 48% of our patients had CD4 counts below 200 cells/microl and these patients showed a marked elevation of FOXP3 percentage (median 10% range 4.07%-26.27%). Assessing the mechanism of increased FOXP3 frequency, we found that the high FOXP3 levels noted in HIV infected individuals dropped rapidly in unstimulated culture conditions but could be restimulated by T cell receptor stimulation. This suggests that the high FOXP3 expression in HIV infected patients is likely due to FOXP3 upregulation by individual CD4(+) T cells following antigenic or other stimulation.FOXP3 expression in the CD4(+) T cell population is a marker of severity of HIV infection and a potential prognostic marker of disease progression

Sura Gamla Kyrka : analysis of pathological and skeletal changes in seven individuals

Seven individuals from Surahammar in Västmanland Sweden are analyzed for the appearance of pathological and skeletal changes. The graves, all from within the walls of a fourteenth century church, are dated from the Viking age to late eighteenth century. The aim of this scientific essay is to find pathological conditions by doing an osteological analyze, x-ray analysis, an osteoporosis measurement and letting orthopedists assess the individuals. The aim is also to say something about the individuals’ general health and how they experience the changes they have in the skeleton. The various types of methods of analysis could confirm and add information to the osteological analysis and in some cases they had different diagnosis. All of the individuals had pathological changes in their upper and/or lower jaw with caries, calculus or apical periodontitis. Among several pathological and skeletal changes three individuals were diagnosed with osteoarthritis in their cervical vertebrae and one in the hip, one had enamel hypoplasia. One individual had both old and new fractures and two individuals had some bone density loss. But despite this their general health was very likely not bad and most of them could live a good life.Caroline Groth, Department of archaeology and osteology, Gotland University, 2010.Sura Gamla Kyrka – Analysis of pathological and skeletal changes in seven individuals.Seven individuals from Surahammar in Västmanland Sweden are analyzed for the appearance of pathological and skeletal changes. The graves, all from within the walls of a fourteenth century church, are dated from the Viking age to late eighteenth century. The aim of this scientific essay is to find pathological conditions by doing an osteological analyze, x-ray analysis, an osteoporosis measurement and letting orthopedists assess the individuals. The aim is also to say something about the individuals’ general health and how they experience the changes they have in the skeleton. The various types of methods of analysis could confirm and add information to the osteological analysis and in some cases they had different diagnosis. All of the individuals had pathological changes in their upper and/or lower jaw with caries, calculus or apical periodontitis. Among several pathological and skeletal changes three individuals were diagnosed with osteoarthritis in their cervical vertebrae and one in the hip, one had enamel hypoplasia. One individual had both old and new fractures and two individuals had some bone density loss. But despite this their general health was very likely not bad and most of them could live a good life.Osteoporosis och osteoarthritis då och n

Sura Gamla Kyrka : analysis of pathological and skeletal changes in seven individuals

Seven individuals from Surahammar in Västmanland Sweden are analyzed for the appearance of pathological and skeletal changes. The graves, all from within the walls of a fourteenth century church, are dated from the Viking age to late eighteenth century. The aim of this scientific essay is to find pathological conditions by doing an osteological analyze, x-ray analysis, an osteoporosis measurement and letting orthopedists assess the individuals. The aim is also to say something about the individuals’ general health and how they experience the changes they have in the skeleton. The various types of methods of analysis could confirm and add information to the osteological analysis and in some cases they had different diagnosis. All of the individuals had pathological changes in their upper and/or lower jaw with caries, calculus or apical periodontitis. Among several pathological and skeletal changes three individuals were diagnosed with osteoarthritis in their cervical vertebrae and one in the hip, one had enamel hypoplasia. One individual had both old and new fractures and two individuals had some bone density loss. But despite this their general health was very likely not bad and most of them could live a good life.Caroline Groth, Department of archaeology and osteology, Gotland University, 2010.Sura Gamla Kyrka – Analysis of pathological and skeletal changes in seven individuals.Seven individuals from Surahammar in Västmanland Sweden are analyzed for the appearance of pathological and skeletal changes. The graves, all from within the walls of a fourteenth century church, are dated from the Viking age to late eighteenth century. The aim of this scientific essay is to find pathological conditions by doing an osteological analyze, x-ray analysis, an osteoporosis measurement and letting orthopedists assess the individuals. The aim is also to say something about the individuals’ general health and how they experience the changes they have in the skeleton. The various types of methods of analysis could confirm and add information to the osteological analysis and in some cases they had different diagnosis. All of the individuals had pathological changes in their upper and/or lower jaw with caries, calculus or apical periodontitis. Among several pathological and skeletal changes three individuals were diagnosed with osteoarthritis in their cervical vertebrae and one in the hip, one had enamel hypoplasia. One individual had both old and new fractures and two individuals had some bone density loss. But despite this their general health was very likely not bad and most of them could live a good life.Osteoporosis och osteoarthritis då och n

Sura Gamla Kyrka : analysis of pathological and skeletal changes in seven individuals

Seven individuals from Surahammar in Västmanland Sweden are analyzed for the appearance of pathological and skeletal changes. The graves, all from within the walls of a fourteenth century church, are dated from the Viking age to late eighteenth century. The aim of this scientific essay is to find pathological conditions by doing an osteological analyze, x-ray analysis, an osteoporosis measurement and letting orthopedists assess the individuals. The aim is also to say something about the individuals’ general health and how they experience the changes they have in the skeleton. The various types of methods of analysis could confirm and add information to the osteological analysis and in some cases they had different diagnosis. All of the individuals had pathological changes in their upper and/or lower jaw with caries, calculus or apical periodontitis. Among several pathological and skeletal changes three individuals were diagnosed with osteoarthritis in their cervical vertebrae and one in the hip, one had enamel hypoplasia. One individual had both old and new fractures and two individuals had some bone density loss. But despite this their general health was very likely not bad and most of them could live a good life.Caroline Groth, Department of archaeology and osteology, Gotland University, 2010.Sura Gamla Kyrka – Analysis of pathological and skeletal changes in seven individuals.Seven individuals from Surahammar in Västmanland Sweden are analyzed for the appearance of pathological and skeletal changes. The graves, all from within the walls of a fourteenth century church, are dated from the Viking age to late eighteenth century. The aim of this scientific essay is to find pathological conditions by doing an osteological analyze, x-ray analysis, an osteoporosis measurement and letting orthopedists assess the individuals. The aim is also to say something about the individuals’ general health and how they experience the changes they have in the skeleton. The various types of methods of analysis could confirm and add information to the osteological analysis and in some cases they had different diagnosis. All of the individuals had pathological changes in their upper and/or lower jaw with caries, calculus or apical periodontitis. Among several pathological and skeletal changes three individuals were diagnosed with osteoarthritis in their cervical vertebrae and one in the hip, one had enamel hypoplasia. One individual had both old and new fractures and two individuals had some bone density loss. But despite this their general health was very likely not bad and most of them could live a good life.Osteoporosis och osteoarthritis då och n