Initiation of an anal cancer screening in HIV+MSM: results of cytology, biopsy and determination of risk factors

Incidence of anal cancer is increasing and risk of anal cancer is higher in MSM, especially if they are HIV+. European guidelines for treatment of HIV-infected adults recommend anal cancer screening by digital rectal exam±Pap test with anuscopy if Pap test is abnormal. A systematic anal cancer screening in HIV+MSM with anal cytology (Pap smears) was established in June 2011 in our reference centre in Brussels. If anal cytology was abnormal, high-resolution anuscopy (HRA) with biopsy was performed. 353 MSM HIV+were screened by anal smears between June 2011 and May 2012. 90% were Caucasians, median age was 44.5 years, 83% were on HAART and 74% had an undetectable viral load, median CD4 was 632/µl and 33% had a nadir CD4<200. Thirty-three (9.3%) were excluded because of poor quality. Cytology was abnormal in 46% of the 320 remaining patients: high-grade squamous intraepithelial lesion (HSIL) 3%, low-grade squamous intraepithelial lesion (LSIL) 24%, atypical squamous cells of undetermined significance (ASC-US) 16%, and atypical squamous cells / cannot rule out a high-grade lesion (ASC-H) 3%. Viral load (VL) was more frequently undetectable (82% vs 64%, p=0.0003) and median duration of HAART was longer (111 vs 61 months, p=0.0145) in patients with normal cytology. 80 HRA with biopsies have been performed. 12.5% were normal, 44% showed anal intraepithelial neoplasia (AIN) 1, 24% AIN 2 and 19% AIN 3. For this analysis, high-grade AIN (2 and 3) were put together (AIN 2+). Among patients with AIN 2+(n=33), cytology had showed 8 (24%) ASC-US, 3 (9%) ASC-H, 19 (57%) LSIL, 3 (9%) HSIL. When patients with normal cytology or normal biopsy and patients with AIN 2+were compared, the only significant risk factor found for AIN 2+was a nadir CD4<100/µl (32% of the patients with AIN 2+vs 14% in patients with normal smear, p=0.0073). Anal precancerous lesions are frequent and at different stages. Among 46% abnormal cytology, 87% had abnormal biopsy including half AIN 2+.Cytology±biopsy is the only way to detect those lesions and should be performed systematically in HIV+MSM. Risk factor for AIN2+was a nadir CD4<100/µl. A normal cytology was associated with an undetectable VL and a longer duration of HAART. Those results provide further argument for early initiation of HAART

Climate driven life histories: the case of the Mediterranean Storm petrel

Seabirds are affected by changes in the marine ecosystem. The influence of climatic factors on marine food webs can be reflected in long-term seabird population changes. We modelled the survival and recruitment of the Mediterranean storm petrel (Hydrobates pelagicus melitensis) using a 21-year mark-recapture dataset involving almost 5000 birds. We demonstrated a strong influence of prebreeding climatic conditions on recruitment age and of rainfall and breeding period conditions on juvenile survival. The results suggest that the juvenile survival rate of the Mediterranean subspecies may not be negatively affected by the predicted features of climate change, i.e., warmer summers and lower rainfall. Based on considerations of winter conditions in different parts of the Mediterranean, we were able to draw inferences about the wintering areas of the species for the first time

Generation and characterization of a defective HIV-1 Virus as an immunogen for a therapeutic vaccine

BACKGROUND: The generation of new immunogens able to elicit strong specific immune responses remains a major challenge in the attempts to obtain a prophylactic or therapeutic vaccine against HIV/AIDS. We designed and constructed a defective recombinant virus based on the HIV-1 genome generating infective but non-replicative virions able to elicit broad and strong cellular immune responses in HIV-1 seropositive individuals. RESULTS: Viral particles were generated through transient transfection in producer cells (293-T) of a full length HIV-1 DNA carrying a deletion of 892 base pairs (bp) in the pol gene encompassing the sequence that codes for the reverse transcriptase (NL4-3/ΔRT clone). The viral particles generated were able to enter target cells, but due to the absence of reverse transcriptase no replication was detected. The immunogenic capacity of these particles was assessed by ELISPOT to determine γ-interferon production in a cohort of 69 chronic asymptomatic HIV-1 seropositive individuals. Surprisingly, defective particles produced from NL4-3/ΔRT triggered stronger cellular responses than wild-type HIV-1 viruses inactivated with Aldrithiol-2 (AT-2) and in a larger proportion of individuals (55% versus 23% seropositive individuals tested). Electron microscopy showed that NL4-3/ΔRT virions display immature morphology. Interestingly, wild-type viruses treated with Amprenavir (APV) to induce defective core maturation also induced stronger responses than the same viral particles generated in the absence of protease inhibitors. CONCLUSIONS: We propose that immature HIV-1 virions generated from NL4-3/ΔRT viral clones may represent new prototypes of immunogens with a safer profile and stronger capacity to induce cellular immune responses than wild-type inactivated viral particles.This study was supported by grants FIS PI050265, FIS PI040503, FIS PI070291, FIS Intrasalud 080752, FIS PS09/01297, FIS PI10/02984, SAF2006-26667-E, FIT 09-010-205-9, FIPSE 36780/08, Fundación Mútua Madrileña, TRA-094, EC10-153, ISCIII-RETIC RD06/0006, HIVACAT–HIV Development Program in Catalonia, FIPSE 36630/07, UE Program Health 2009 CHAARM. Spanish Health Institute Carlos III (ISCIII) and the Health Department of the Catalan Government (Generalitat de Catalunya). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Overview paper: New insights into aerosol and climate in the Arctic

Motivated by the need to predict how the Arctic atmosphere will change in a warming world, this article summarizes recent advances made by the research consortium NETCARE (Network on Climate and Aerosols: Addressing Key Uncertainties in Remote Canadian Environments) that contribute to our fundamental understanding of Arctic aerosol particles as they relate to climate forcing. The overall goal of NETCARE research has been to use an interdisciplinary approach encompassing extensive field observations and a range of chemical transport, earth system, and biogeochemical models. Several major findings and advances have emerged from NETCARE since its formation in 2013. (1) Unexpectedly high summertime dimethyl sulfide (DMS) levels were identified in ocean water (up to 75&thinsp;nM) and the overlying atmosphere (up to 1&thinsp;ppbv) in the Canadian Arctic Archipelago (CAA). Furthermore, melt ponds, which are widely prevalent, were identified as an important DMS source (with DMS concentrations of up to 6&thinsp;nM and a potential contribution to atmospheric DMS of 20&thinsp;% in the study area). (2) Evidence of widespread particle nucleation and growth in the marine boundary layer was found in the CAA in the summertime, with these events observed on 41&thinsp;% of days in a 2016 cruise. As well, at Alert, Nunavut, particles that are newly formed and grown under conditions of minimal anthropogenic influence during the months of July and August are estimated to contribute 20&thinsp;% to 80&thinsp;% of the 30–50&thinsp;nm particle number density. DMS-oxidation-driven nucleation is facilitated by the presence of atmospheric ammonia arising from seabird-colony emissions, and potentially also from coastal regions, tundra, and biomass burning. Via accumulation of secondary organic aerosol (SOA), a significant fraction of the new particles grow to sizes that are active in cloud droplet formation. Although the gaseous precursors to Arctic marine SOA remain poorly defined, the measured levels of common continental SOA precursors (isoprene and monoterpenes) were low, whereas elevated mixing ratios of oxygenated volatile organic compounds (OVOCs) were inferred to arise via processes involving the sea surface microlayer. (3) The variability in the vertical distribution of black carbon (BC) under both springtime Arctic haze and more pristine summertime aerosol conditions was observed. Measured particle size distributions and mixing states were used to constrain, for the first time, calculations of aerosol–climate interactions under Arctic conditions. Aircraft- and ground-based measurements were used to better establish the BC source regions that supply the Arctic via long-range transport mechanisms, with evidence for a dominant springtime contribution from eastern and southern Asia to the middle troposphere, and a major contribution from northern Asia to the surface. (4) Measurements of ice nucleating particles (INPs) in the Arctic indicate that a major source of these particles is mineral dust, likely derived from local sources in the summer and long-range transport in the spring. In addition, INPs are abundant in the sea surface microlayer in the Arctic, and possibly play a role in ice nucleation in the atmosphere when mineral dust concentrations are low. (5) Amongst multiple aerosol components, BC was observed to have the smallest effective deposition velocities to high Arctic snow (0.03&thinsp;cm&thinsp;s−1).</p