The information analysis center concept as developed by the Radiation Shielding Information Center in its computer codes activities

Information analysis center concept and computer codes for calculating radiation transport, and shield design

VACUTAINER(® )CPT™ and Ficoll density gradient separation perform equivalently in maintaining the quality and function of PBMC from HIV seropositive blood samples

BACKGROUND: For immune monitoring studies during HIV vaccine clinical trials, whole blood specimens from HIV seropositive (HIV(+)) patients may be collected at multiple sites and sent to a central location for peripheral blood mononuclear cell (PBMC) isolation, cryopreservation and functional evaluation. In this study we show a comparison of two PBMC preparation options, Ficoll density gradient separation (Ficoll) and Cell Preparation Tubes (CPT) using shipped whole blood specimens from 19 HIV(+ )patients (CD4 > 350, viral load < 50). The pre- and post- cryopreservation performance of samples collected by these two methods were compared by assessment of antigen-specific IFNγ expression in CD8(+ )and CD8(- )T cells, cellular viability, and cellular recovery. RESULTS: The results indicate that cryopreserved PBMC samples tested for CMV- and HIV- specific interferon-gamma (IFNγ) expression performed equivalent to the respective fresh PBMC processed under both collection conditions. Compared to fresh PBMC, the viability was significantly lower for cryopreserved PBMC derived using Ficoll, although it was never less than 90%. There were no significant differences in the IFNγ response, viability, or recovery between cryopreserved PBMC derived by Ficoll and by CPT. CONCLUSION: These data suggest that CPT is an efficient system for the collection and cryopreservation of functionally active HIV(+ )PBMC, as well as a viable alternative to Ficoll gradient separation

Monitoring processed, mature Human Immunodeficiency Virus type 1 particles immediately following treatment with a protease inhibitor-containing treatment regimen

Protease inhibitors (PIs) block HIV-1 maturation into an infectious virus particle by inhibiting the protease processing of gag and gag-pol precursor proteins. We have used a simple anti-HIV-1 p24 Western blot to monitor the processing of p55(gag )precursor into the mature p24 capsid immediately following the first dosage of a PI-containing treatment regimen. Evidence of PI activity was observed in plasma virus as early as 72 hours post treatment-initiation and was predictive of plasma viral RNA decrease at 4 weeks

Safety and immunogenicity of H1/IC31®, an adjuvanted TB subunit vaccine, in HIV-infected adults with CD4+ lymphocyte counts greater than 350 cells/mm3: a phase II, multi-centre, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Novel tuberculosis vaccines should be safe, immunogenic, and effective in various population groups, including HIV-infected individuals. In this phase II multi-centre, double-blind, placebo-controlled trial, the safety and immunogenicity of the novel H1/IC31 vaccine, a fusion protein of Ag85B-ESAT-6 (H1) formulated with the adjuvant IC31, was evaluated in HIV-infected adults. METHODS: HIV-infected adults with CD4+ T cell counts >350/mm3 and without evidence of active tuberculosis were enrolled and followed until day 182. H1/IC31 vaccine or placebo was randomly allocated in a 5:1 ratio. The vaccine was administered intramuscularly at day 0 and 56. Safety assessment was based on medical history, clinical examinations, and blood and urine testing. Immunogenicity was determined by a short-term whole blood intracellular cytokine staining assay. RESULTS: 47 of the 48 randomised participants completed both vaccinations. In total, 459 mild or moderate and 2 severe adverse events were reported. There were three serious adverse events in two vaccinees classified as not related to the investigational product. Local injection site reactions were more common in H1/IC31 versus placebo recipients (65.0% vs. 12.5%, p = 0.015). Solicited systemic and unsolicited adverse events were similar by study arm. The baseline CD4+ T cell count and HIV viral load were similar by study arm and remained constant over time. The H1/IC31 vaccine induced a persistent Th1-immune response with predominately TNF-α and IL-2 co-expressing CD4+ T cells, as well as polyfunctional IFN-γ, TNF-α and IL-2 expressing CD4+ T cells. CONCLUSION: H1/IC31 was well tolerated and safe in HIV-infected adults with a CD4+ Lymphocyte count greater than 350 cells/mm3. The vaccine did not have an effect on CD4+ T cell count or HIV-1 viral load. H1/IC31 induced a specific and durable Th1 immune response. TRIAL REGISTRATION: Pan African Clinical Trials Registry (PACTR) PACTR201105000289276

Applying a User-centred Approach to Interactive Visualization Design

Analysing users in their context of work and finding out how and why they use different information resources is essential to provide interactive visualisation systems that match their goals and needs. Designers should actively involve the intended users throughout the whole process. This chapter presents a user-centered approach for the design of interactive visualisation systems. We describe three phases of the iterative visualisation design process: the early envisioning phase, the global specification hase, and the detailed specification phase. The whole design cycle is repeated until some criterion of success is reached. We discuss different techniques for the analysis of users, their tasks and domain. Subsequently, the design of prototypes and evaluation methods in visualisation practice are presented. Finally, we discuss the practical challenges in design and evaluation of collaborative visualisation environments. Our own case studies and those of others are used throughout the whole chapter to illustrate various approaches

Microscopic Models for Chemical Thermodynamics

We introduce an infinite particle system dynamics, which includes stochastic chemical kinetics models, the classical Kac model and free space movement. We study energy redistribution between two energy types (kinetic and chemical) in different time scales, similar to energy redistribution in the living cell. One example is considered in great detail, where the model provides main formulas of chemical thermodynamics

Patterns within Patterns within the Smart Living Experience

Modern technology is increasingly being employed to create a “smart” living experience. These “smart” technology entities are producing copious of amounts data, which in turn rely on increased storage, distribution and computation capacity to manage the data. Depending on the scenario, the diversity of piecemeal solutions almost reflects the diversity of problems they address. But some solutions can be reapplied. In the field of computing, design patterns can provide a general, reusable solution to commonly recurring problems within a given context through software design. This work seeks to determine the core elements of a technology-independent design pattern format and an open software framework can be developed to capture, share and redeploy existing successful and reusable strategies for commonly encountered smart environment use cases. Applying in areas such as assistive technology, energy management and environmental monitoring. The underpinning notion of this paper is to introduce “how, where and why” a rule set based in “design pattern” format could contribute to describe a general “understanding” of given cases in the smart environment domain, as well as allow different processes to collaborate with each other

Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques

Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX) and of gut inflammation (Sulfasalazine-SFZ). RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs) starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab–infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection

Shipment Impairs Lymphocyte Proliferative Responses to Microbial Antigens

Lymphocyte proliferation assays (LPAs) are widely used to assess T-lymphocyte function of patients with human immunodeficiency virus infection and other primary and secondary immunodeficiency disorders. Since these assays require expertise not readily available at all clinical sites, specimens may be shipped to central labs for testing. We conducted a large multicenter study to evaluate the effects of shipping on assay performance and found significant loss of LPA activity. This may lead to erroneous results for individual subjects and introduce bias into multicenter trials

T-Cell Immune Dysregulation and Mortality in Women with Human Immunodeficiency Virus

Summary: In women with HIV, higher activation and exhaustion of CD4+ T cells were associated with risk of non-HIV-related mortality during a median of 13.3 years of follow-up, independent of baseline demographic, behavioral, HIV-related, and cardiometabolic factors and longitudinal HIV disease progression. Background: Dysregulation of adaptive immunity is a hallmark of human immunodeficiency virus (HIV) infection that persists on antiretroviral therapy (ART). Few long-term prospective studies have related adaptive immunity impairments to mortality in HIV, particularly in women. Methods: Among 606 women with HIV in the Women's Interagency HIV Study, peripheral blood mononuclear cells collected from 2002 to 2005 underwent multiparameter flow cytometry. Underlying cause of death was ascertained from the National Death Index up to 2018. We examined associations of CD4+ and CD8+ T-cell activation (%CD38+HLA-DR+), senescence (%CD57+CD28-), exhaustion (%PD-1+), and nonactivation/normal function (%CD57-CD28+) with natural-cause, HIV-related, and non-HIV-related mortality. Results: At baseline, median participant age was 41, and 67% were on ART. Among 100 deaths during a median of 13.3 years follow-up, 90 were natural-cause (53 non-HIV-related, 37 HIV-related). Higher activation and exhaustion of CD4+ T cells were associated with risk of natural-cause and non-HIV-related mortality, adjusting for age, demographic, behavioral, HIV-related, and cardiometabolic factors at baseline. Additional adjustment for time-varying viral load and CD4+ T-cell count did not attenuate these associations. CD8+ T-cell markers were not associated with any outcomes adjusting for baseline factors. Conclusions: Persistent CD4+ T-cell activation and exhaustion may contribute to excess long-term mortality risk in women with HIV, independent of HIV disease progression