Role of In Vitro Stimulation with Lipopolysaccharide on T-Cell Activation in HIV-Infected Antiretroviral-Treated Patients

We investigated the effect of LPS in vitro stimulation on T-cell activation in HIV-infected patients with different CD4+ recovery on HAART. PBMCs from 30 HIV-positive, HAART-treated, aviremic individuals with different CD4+ reconstitution (Low Responders: CD4+ < 350/μL; Intermediate Responders: CD4+ 350–599/μL; High Responders: CD4+ ≥ 600/μL) were cultured with LPS and the proportion of HLA-DR/CD38- and Ki67-expressing CD4+/CD8+ T-cells was measured (flow cytometry). Upon LPS stimulation, significantly higher CD4+ and CD8+HLA-DR+ cells were shown in LR and IR versus HIV-negative controls. While no differences in the proportion of LPS-stimulated CD4+CD38+ cells were recorded amongst HIV-positive subgroups, CD8+CD38+ cells were more elevated in patients with lower CD4+ recovery on HAART (i.e., LR and IR). Upon in vitro LPS stimulation, HLA-DR and CD38 expression on T-cells are differentially regulated. While HLA-DR induction reflects impaired CD4+ reconstitution on HAART, cell-surface CD38 expression is increased only on CD8+ T-cells, allowing to speculate that the sole induction of CD38 on CD4+ cells may not be sufficient to depict LPS-driven immune activation in HIV

test of cloud federation in chain reds project

Cloud Computing is considered a successful technology, involving distributed computation infrastructures, which take advantage of the virtualization of physical resources to actuate useful scale economies. In cloud ecosystems today, attention increasingly focuses on cooperation issues, mostly in the wider context of federation. Cloud federation refers to the process of interconnecting different cloud infrastructures for resource load balancing and to manage demand spikes. One of the biggest advantages of a federated cloud consists of the possibility of distributing the workload over different cloud providers, rather than obtaining cloud services from just a single supplier. In addition, federation could be very important for Big Data, for example, to implement policies allowing migration for virtual machines involved in data analysis next to storage hosting Big Data. Federation, automation, standards, and interoperability are crucial for cloud computing services to be successful in the near future. Standards are crucial for both interoperability and federation, and federation is the first step toward interoperability. The idea we describe in this paper comes from the assumption that some of Cloud Infrastructure offering IaaS (e.g., OpenStack, OpenNebula) provide interfaces based on the OCCI standard, but lack an interconnecting cooperation/federation awareness layer. We propose a software infrastructure able to provide a homogeneous interface among different Cloud managers, in order to coordinate the IaaS resources in a transparent and distributed manner. We have implemented such software, based on CLEVER, a novel Cloud Middleware jointly developed by INFN Catania and the University of Messina, which uses XMPP as interconnecting communication protocol. We also present: an interface for the Catania Science Gateway Framework implementing a simple dashboard a testbed used in the framework of the CHAIN-REDS Project, which includes sites belonging to the EGI Federated Cloud. This work shows that cloud federation using standards is feasible

A Model for Accomplishing and Managing Dynamic Cloud Federations

Cloud computing is not just a promising approach to the service provisioning: nowadays it represents the reference model in such field. Several cloud service providers have emerged as de facto standards and an increasing number of companies are choosing to migrate their business in the Cloud "ecosystem". Nevertheless, each provider adopts a particular interface to manage its services and uses a proprietary technology. In this paper we present a cloud federation model which is able to provide scalability and flexibility to small clouds. The idea is to benefit of renting seamless resources according to federation agreements among operators. The challenge here is to overcome all the problems raising trying to merge small clouds with heterogeneous administrative domains

Current models of care for the management of HIV patients with comorbidities in England: a survey

Introduction: The number of people aged ]50 living with HIV in the UK is rapidly increasing. Effective treatment means HIV is usually well controlled; however, there has been an increase in individuals experiencing comorbid conditions associated with ‘‘normal’’ ageing. This aim of this study was to find out what models of care are currently in place for the management of patients with comorbidities. Materials and methods: A link to an online questionnaire was sent via the British HIV Association (BHIVA) Audit Committee to one HIV clinician in each HIV unit in England. Results: Forty-four units responded. Only 11 units (25%) provided specialized clinics for the management of comorbidities. These included: 1) Specialist clinics for the management of a non-infectious comorbidity (any age) e.g. a liver or renal clinic (n10). These clinics utilized in-person appointments (n3), or a combination of virtual and in-person appointments (n7). They were managed by an HIV clinician and non-HIV clinician together (n8), HIV clinician with an interest in the specialist area (n4) or specialist with an interest in HIV (n4). 2) Services for HIV patients with multiple comorbidities (any age) (n2). 3) Dedicated clinics for older people (n5) with eligibility determined by age (]50 years) or the presence of a comorbidity. Additionally, two HIV units employed a GP on site and two had set up a locally enhanced service providing enhanced primary care for HIV-positive patients. Six HIV units ran nurse-led clinics for patients with comorbid conditions. Co-ordination of care for patients with comorbid conditions was conducted by an HIV specialist doctor (n27), the patient’s GP (n18), HIV specialist nurse (n11) or the patient themselves (n9). Eleven clinics reported using case management for patients with multiple comorbid conditions. Self-management support (e.g. nurse-led or as part of an expert patient programme) for patients with comorbid conditions was provided at 18 HIV units. Conclusions: Only a quarter of the clinics surveyed had set up clinics for the management of comorbidities in people living with HIV. While a variety of different approaches were used, services were usually focused on the management of one comorbidity, and few provided services for multiple comorbidities. This is an increasing priority in the context of an ageing population. P162 Th

Prognostic value of the fibrosis-4 index in human immunodeficiency virus type-1 infected patients initiating antiretroviral therapy with or without hepatitis C virus

Objective: To evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART). Design: Retrospective analysis of a prospective cohort study. Setting: Italian HIV care centers participating to the ICONA Foundation cohort. Participants: Treatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up. Methods: Cox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD. Results: Three-thousand four-hundred seventy-five patients were enrolled: 73.3% were males, 27.2% HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/mL, 65.9% had a FIB-4 &lt;1.45, 26.4% 1.45–3.25 and 7.7% &gt;3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95% confidence interval, CI 1.6–3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to &lt;1.45 (FIB-4 1.45–3.25: HR 3.55, 95% CI 1.09–11.58; FIB-4 &gt;3.25: HR 4.25, 1.21–14.92) and time-updated FIB-4 (FIB-4 1.45–3.25: HR 3.40, 1.02–11.40; FIB-4 &gt;3.25: HR 21.24, 6.75–66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART. Conclusions: The FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART

What Is the Exact Contribution of PITX1 and TBX4 Genes in Clubfoot Development? An Italian Study

Congenital clubfoot is a common pediatric malformation that affects approximately 0.1% of all births. 80% of the cases appear isolated, while 20% can be secondary or associated with complex syndromes. To date, two genes that appear to play an important role are PTIX1 and TBX4, but their actual impact is still unclear. Our study aimed to evaluate the prevalence of pathogenic variants in PITX1 and TBX4 in Italian patients with idiopathic clubfoot. PITX1 and TBX4 genes were analyzed by sequence and SNP array in 162 patients. We detected only four nucleotide variants in TBX4, predicted to be benign or likely benign. CNV analysis did not reveal duplications or deletions involving both genes and intragenic structural variants. Our data proved that the idiopathic form of congenital clubfoot was rarely associated with mutations and CNVs on PITX1 and TBX4. Although in some patients, the disease was caused by mutations in both genes; they were responsible for only a tiny minority of cases, at least in the Italian population. It was not excluded that other genes belonging to the same TBX4-PITX1 axis were involved, even if genetic complexity at the origin of clubfoot required the involvement of other factors

Determinants of access to experimental antiretroviral drugs in an Italian cohort of patients with HIV: a multilevel analysis

<p>Abstract</p> <p>Background</p> <p>Identification of the determinants of access to investigational drugs is important to promote equity and scientific validity in clinical research. We aimed to analyze factors associated with the use of experimental antiretrovirals in Italy.</p> <p>Methods</p> <p>We studied participants in the Italian Cohort of Antiretroviral-Naive Patients (ICoNA). All patients 18 years or older who had started cART (≥ 3 drugs including at least two NRTI) after their enrolment and during 1997-2007 were included in this analysis. We performed a random effect logistic regression analysis to take into account clustering observations within clinical units. The outcome variable was the use of an experimental antiretroviral, defined as an antiretroviral started before commercial availability, in any episode of therapy initiation/change. Use of an experimental antiretroviral obtained through a clinical trial or an expanded access program (EAP) was also analyzed separately.</p> <p>Results</p> <p>A total of 9,441 episodes of therapy initiation/change were analyzed in 3,752 patients. 392 episodes (360 patients) involved an experimental antiretroviral. In multivariable analysis, factors associated with the overall use of experimental antiretrovirals were: number of experienced drugs (≥ 8 drugs versus "naive": adjusted odds ratio [AOR] = 3.71) or failed antiretrovirals(3-4 drugs and ≥ 5 drugs versus 0-2 drugs: AOR = 1.42 and 2.38 respectively); calendar year (AOR = 0.80 per year) and plasma HIV-RNA copies/ml at therapy change (≥ 4 log versus < 2 log: AOR = 1.55). The probability of taking an experimental antiretroviral through a trial was significantly lower for patients suffering from liver co-morbidity(AOR = 0.65) and for those who experienced 3-4 drugs (vs naive) (AOR = 0.55), while it increased for multi-treated patients(AOR = 2.60). The probability to start an experimental antiretroviral trough an EAP progressively increased with the increasing number of experienced and of failed drugs and also increased for patients with liver co-morbidity (AOR = 1.44; p = 0.053). and for male homosexuals (vs heterosexuals: AOR = 1.67). Variability of the random effect associated to clinical units was statistically significant (p < 0.001) although no association was found with specific characteristics of clinical unit examined.</p> <p>Conclusions</p> <p>Among patients with HIV infection in Italy, access to experimental antiretrovirals seems to be influenced mainly by exhaustion of treatment options and not by socio-demographic factors.</p

The Sicilian Grid Infrastructure for High Performance Computing

The conjugation of High Performance Computing (HPC) and Grid paradigm with applications based on commercial software is one among the major challenges of today e-Infrastructures. Several research communities from either industry or academia need to run high parallel applications based on licensed software over hundreds of CPU cores; a satisfactory fulfillment of such requests is one of the keys for the penetration of this computing paradigm into the industry world and sustainability of Grid infrastructures. This problem has been tackled in the context of the PI2S2 project that created a regional e-Infrastructure in Sicily, the first in Italy over a regional area. Present article will describe the features added in order to integrate an HPC facility into the PI2S2 Grid infrastructure, the adoption of the InifiniBand low-latency net connection, the gLite middleware extended to support MPI/MPI2 jobs, the newly developed license server and the specific scheduling policy adopted. Moreover, it will show the results of some relevant use cases belonging to Computer Fluid-Dynamics (Fluent, OpenFOAM), Chemistry (GAMESS), Astro-Physics (Flash) and Bio-Informatics (ClustalW))

The Sicilian Grid Infrastructure for High Performance Computing

The conjugation of High Performance Computing (HPC) and Grid paradigm with applications based on commercial software is one among the major challenges of today e-Infrastructures. Several research communities from either industry or academia need to run high parallel applications based on licensed software over hundreds of CPU cores; a satisfactory fulfillment of such requests is one of the keys for the penetration of this computing paradigm into the industry world and sustainability of Grid infrastructures. This problem has been tackled in the context of the PI2S2 project that created a regional e-Infrastructure in Sicily, the first in Italy over a regional area. Present paper will describe the features added in order to integrate an HPC facility into the PI2S2 Grid infrastructure, the adoption of the InifiniBand low-latency net connection, the gLite middleware extended to support MPI/MPI2 jobs, the newly developed license server and the specific scheduling policy adopted. Moreover, it will show the results of some relevant use cases belonging to Computer Fluid-Dynamics (Fluent, OpenFOAM), Chemistry (GAMESS), Astro-Physics (Flash) and Bio-Informatics (ClustalW))

Renal function in HIV-infected children and adolescents treated with tenofovir disoproxil fumarate and protease inhibitors

<p>Abstract</p> <p>Background</p> <p>Kidney disease is an important complication in HIV infected people, and this may be related to infection or antiretroviral therapy (ART). Our aim is to assess renal function in HIV infected paediatric patients, who may be particularly affected and are likely to take ART for longer than adults, and investigate the long term role of Tenofovir Disoproxil Fumarate (TDF) alone or co-administered with Ritonavir-boosted Protease Inhibitors (PI).</p> <p>Methods</p> <p>Serum creatinine, phosphate and potassium levels, with estimated Glomerular Filtration Rate (eGFR), had been prospectively evaluated for 2 years in a cohort of HIV infected children and adolescents (age 9-18) on ART, and data analyzed according to the exposure to TDF or simultaneous TDF and PI.</p> <p>Results</p> <p>Forty-nine patients were studied (57% female, mean age 14). Sixty-three percent were treated with ART containing TDF (Group A), and 37% without TDF (Group B); 47% with concomitant use of TDF and PI (Group C) and 53% without this combination (Group D). The groups didn't differ for age, gender or ethnicity. The median creatinine increased in the entire cohort and in all the groups analyzed; eGFR decreased from 143.6 mL/min/1.73 m²at baseline to 128.9 after 2 years (<it>p </it>= 0.006) in the entire cohort. Three patients presented a mild eGFR reduction, all were on TDF+PI. Phosphatemia decreased significantly in the entire cohort (<it>p </it>= 0.0003) and in TDF+PI group (<it>p </it>= 0.0128) after 2 years. Five patients (10%) developed hypophosphatemia (Division of Acquired Immune Deficiency AE grade 1 or 2), and four of them were on TDF+PI.</p> <p>Conclusions</p> <p>Renal function decrease and hypophosphatemia occur over time in HIV infected children and adolescents on ART. The association with co-administration of TDF and PI appears weak, and further studies are warranted.</p