bluuebunny/crossref_metadata_2025 huggingface dataset:
Les modes de discours, interface entre texte et grammaire dans les langues de spécialité
Authors: Pic Elsa , Furmaniak Grégory
Published: November 2012

Notre objectif est de présenter les apports que constituent pour l’étude grammaticale des langues de spécialité les « modes de discours » (Smith 2003). Nous montrons que, parce que les modes de discours sont définis à la fois formellement et sémantiquement, ils constituent un niveau d’analyse intermédiaire susceptible d’éclairer les rapports indirects entre les phénomènes grammaticaux de niveau phrastique et le fonctionnement pragmatico-discursif des textes. Les modes de discours possèdent deux avantages sur d’autres typologies existantes : leur caractère général les rend pertinents pour tout type de texte, y compris pour les textes vulgarisés, qui constituent la moitié de notre corpus, tandis que leur nombre réduit en fait un outil gérable et opératoire. Toutefois, le manque d’assise empirique du modèle de C. Smith ne lui permet pas de rendre compte d’un éventail suffisant de genres et de sous-genres et nécessite donc l’ajout de modes supplémentaires. En outre, bien que C. Smith attribue aux modes de discours des propriétés formelles et sémantico-pragmatiques, ce dernier aspect reste largement programmatique. C’est donc dans les théories françaises du discours que nous puisons pour pallier ces deux lacunes. Nous concluons par une analyse du hedging en discours spécialisé et en discours vulgarisé qui illustre la manière dont les modes de discours sont exploitables pour caractériser les propriétés linguistiques des textes.
Research in electronically-mediated communication in professional contexts – revisiting the past, preparing for the future
Authors: Gimenez Julio
Published: November 2012

Cet article fait l’état des lieux des apports que l’étude du domaine de la communication véhiculée par l’électronique a eu en ce qui concerne notre compréhension de la nature et des objectifs de la communication en contexte professionnel. Il analyse les possibilités créées par les avancées technologiques récentes. L’article clôt sur un programme de recherches futures dans le domaine la communication véhiculée par l’électronique. Il met en avant la façon dont les thèmes ainsi que les activités dans ce programme peuvent être reliés aux quatre axes épistémologiques discutés lors du 33e colloque du GERAS : langue et discours, didactique, culture et technologie.
From informal resource usage to incidental language acquisition: language uptake from online television viewing in English
Authors: Kusyk Meryl , Sockett Geoffrey
Published: November 2012

La recherche dans le domaine de l’apprentissage informel de l’anglais en ligne a mis en évidence le fait que ce phénomène est courant chez les apprenants d’anglais du secteur Lansad dans les universités françaises. La langue à laquelle ces apprenants sont exposés lors de visionnages de séries télévisées en version originale par le biais du streaming ou du téléchargement a aussi été caractérisée et quantifiée. Dans la présente étude, des apprenants ont d’abord répondu à un questionnaire pour déterminer la fréquence à laquelle ils visionnent de tels contenus. Ils ont ensuite participé à un test dans lequel ils se sont servis d’une échelle de connaissance de vocabulaire pour indiquer leur degré de connaissance d’une série de phrases incorporant les blocs de quatre mots les plus fréquents dans les dialogues de ces séries. Les résultats indiquent un écart significatif dans les scores à ce test entre ceux qui visionnent fréquemment ces séries, et ceux qui ne les visionnent qu’occasionnellement.
In Vitro Generation of Long-lived Human Plasma Cells
Authors: Cocco Mario , Stephenson Sophie , Care Matthew A. , Newton Darren , Barnes Nicholas A. , Davison Adam , Rawstron Andy , Westhead David R. , Doody Gina M. , Tooze Reuben M.
Published: November 2012

Plasma cells (PCs), the terminal effectors of humoral immunity, are short-lived unless supported by niche environments in which they may persist for years. No model system has linked B cell activation with niche function to allow the in vitro generation of long-lived PCs. Thus, the full trajectory of B cell terminal differentiation has yet to be investigated in vitro. In this article, we describe a robust model for the generation of polyclonal long-lived human PCs from peripheral blood B cells. After a proliferative plasmablast phase, PCs persist in the absence of cell division, with viability limited only by elective culture termination. Conservative predictions for PC life expectancy are 300 d, but with the potential for significantly longer life spans for some cells. These long-lived PCs are preferentially derived from memory B cells, and acquire a CD138high phenotype analogous to that of human bone marrow PCs. Analysis of gene expression across the system defines clusters of genes with related dynamics and linked functional characteristics. Importantly, genes in these differentiation clusters demonstrate a similar overall pattern of expression for in vitro and ex vivo PCs. In vitro PCs are fully reprogrammed to a secretory state and are adapted to their secretory load, maintaining IgG secretion of 120 pg/cell/day in the absence of XBP1 mRNA splicing. By establishing a set of conditions sufficient to allow the development and persistence of mature human PCs in vitro, to our knowledge, we provide the first platform with which to sequentially explore and manipulate each stage of human PC differentiation.
Potent Induction of Antibody-Secreting B Cells by Human Dermal-Derived CD14+ Dendritic Cells Triggered by Dual TLR Ligation
Authors: Matthews Katie , Chung Nancy P. Y. , Klasse Per Johan , Moore John P. , Sanders Rogier W.
Published: November 2012

Targeting CD14+ dermal-derived dendritic cells (DDCs) is a rational approach for vaccination strategies aimed at improving humoral immune responses, because of their natural ability to stimulate naive B cells. In this study, we show that CD14+ DDCs express mRNA for TLRs 1–9, but respond differentially to single or paired TLR ligands. Compared to single ligands, some combinations were particularly effective at activating CD14+ DDCs, as shown by enhanced expression of B cell stimulatory cytokines (IL-6, IL-10, and TNF-α) and more pronounced phenotypic maturation. These combinations were resiquimod (R-848) plus polyinosinic-polycytidylic acid [Poly(I:C)], R-848 plus LPS, Pam3CSK4 plus Poly(I:C), and LPS plus Poly(I:C). We also found that selected TLR ligand pairs [R-848 plus either LPS or Poly(I:C)] were superior to individual agents at boosting the inherent capacity of CD14+ DDCs to induce naive B cells to proliferate and differentiate into CD27+ CD38+ B cells that secrete high levels of IgG and IgA. When treated with the same TLR ligand combinations, CD14+ DDCs also promoted the differentiation of Th1 (IFN-γ–secreting) CD4+ T cells, but not of Th2 or Th17 CD4+ T cells. These observations may help to identify adjuvant strategies aimed at inducing protective immune responses to various pathogens, including but not limited to HIV-1.
Environmental and T Cell–Intrinsic Factors Limit the Expansion of Neonatal Follicular T Helper Cells but May Be Circumvented by Specific Adjuvants
Authors: Mastelic Béatris , Kamath Arun T. , Fontannaz Paola , Tougne Chantal , Rochat Anne-Françoise , Belnoue Elodie , Combescure Christophe , Auderset Floriane , Lambert Paul-Henri , Tacchini-Cottier Fabienne , Siegrist Claire-Anne
Published: November 2012

Follicular Th (TFH) cells have emerged as a new Th subset providing help to B cells and supporting their differentiation into long-lived plasma cells or memory B cells. Their differentiation had not yet been investigated following neonatal immunization, which elicits delayed and limited germinal center (GC) responses. We demonstrate that neonatal immunization induces CXCR5highPD-1high CD4+ TFH cells that exhibit TFH features (including Batf, Bcl6, c-Maf, ICOS, and IL-21 expression) and are able to migrate into the GCs. However, neonatal TFH cells fail to expand and to acquire a full-blown GC TFH phenotype, as reflected by a higher ratio of GC TFH/non-GC CD4+ T cells in immunized adults than neonates (3.8 × 10−3 versus 2.2 × 10−3, p = 0.01). Following the adoptive transfer of naive adult OT-II CD4+ T cells, OT-II TFH cells expand in the vaccine-draining lymph nodes of immunized adult but not infant recipients, whereas naive 2-wk-old CD4+ OT-II cells failed to expand in adult hosts, reflecting the influence of both environmental and T cell–intrinsic factors. Postponing immunization to later in life increases the number of TFH cells in a stepwise manner, in direct correlation with the numbers of GC B cells and plasma cells elicited. Remarkably, adjuvantation with CpG oligonucleotides markedly increased GC TFH and GC B cell neonatal responses, up to adult levels. To our knowledge, this is the first demonstration that the TFH cell development limits early life GC responses and that adjuvants/delivery systems supporting TFH differentiation may restore adultlike early life GC B cell responses.
B Lymphocyte–Induced Maturation Protein-1 Contributes to Intestinal Mucosa Homeostasis by Limiting the Number of IL-17–Producing CD4+ T Cells
Authors: Salehi Soofia , Bankoti Rashmi , Benevides Luciana , Willen Jessica , Couse Michael , Silva Joao S. , Dhall Deepti , Meffre Eric , Targan Stephan , Martins Gislâine A.
Published: November 2012

The transcription factor B lymphocyte–induced maturation protein-1 (Blimp-1) plays important roles in embryonic development and immunity. Blimp-1 is required for the differentiation of plasma cells, and mice with T cell–specific deletion of Blimp-1 (Blimp-1CKO mice) develop a fatal inflammatory response in the colon. Previous work demonstrated that lack of Blimp-1 in CD4+ and CD8+ T cells leads to intrinsic functional defects, but little is known about the functional role of Blimp-1 in regulating differentiation of Th cells in vivo and their contribution to the chronic intestinal inflammation observed in the Blimp1CKO mice. In this study, we show that Blimp-1 is required to restrain the production of the inflammatory cytokine IL-17 by Th cells in vivo. Blimp-1CKO mice have greater numbers of IL-17–producing TCRβ+CD4+cells in lymphoid organs and in the intestinal mucosa. The increase in IL-17–producing cells was not restored to normal levels in wild-type and Blimp-1CKO–mixed bone marrow chimeric mice, suggesting an intrinsic role for Blimp-1 in constraining the production of IL-17 in vivo. The observation that Blimp-1–deficient CD4+ T cells are more prone to differentiate into IL-17+/IFN-γ+ cells and cause severe colitis when transferred to Rag1-deficient mice provides further evidence that Blimp-1 represses IL-17 production. Analysis of Blimp-1 expression at the single cell level during Th differentiation reveals that Blimp-1 expression is induced in Th1 and Th2 but repressed by TGF-β in Th17 cells. Collectively, the results described here establish a new role for Blimp-1 in regulating IL-17 production in vivo.
Unlinked Memory Helper Responses Promote Long-Lasting Humoral Alloimmunity
Authors: Conlon Thomas M. , Cole Jennifer L. , Motallebzadeh Reza , Harper Inês , Callaghan Chris J. , Bolton Eleanor M. , Bradley J. Andrew , Saeb-Parsy Kourosh , Pettigrew Gavin J.
Published: November 2012

Essential help for long-lived alloantibody responses is theoretically provided only by CD4 T cells that recognize target alloantigen, processed and presented by the allospecific B cell. We demonstrate that in an alloresponse to multiple MHC disparities, cognate help for class-switched alloantibody may also be provided by CD4 T cells specific for a second “helper” alloantigen. This response was much shorter-lived than when help was provided conventionally, by Th cell recognition of target alloantigen. Nevertheless, long-lasting humoral alloimmunity developed when T cell memory against the helper alloantigen was first generated. Costimulatory blockade abrogated alloantibody produced through naive Th cell recognition of target alloantigen but, crucially, blockade was ineffective when help was provided by memory responses to the accessory helper alloantigen. These results suggest that memory Th cell responses against previously encountered graft alloantigen may be the dominant mechanism for providing help to generate new specificities of alloantibody in transplant patients receiving immunosuppression.
Overview of recent developments in chronic lymphocytic leukemia
Authors: Jain Preetesh , Rai Kanti R.
Published: November 2012

Multiple advances have been made in our understanding of pathobiology of chronic lymphocytic leukemia (CLL). These developments in the laboratory include new prognostic markers, risk stratification of the disease and newer therapeutic agents in CLL. These advances in CLL have come a long way in the past three decades since the development of Rai and Binet clinical staging systems. Important strides in the pathobiology, from defining mutational status of IGHV, to B-cell receptor (BCR) signaling pathways and CLL microenvironment have made a major difference in our understanding of this disease. Mutational status of immunoglobulin heavy chain genes (IGHV), CD38 and Zap-70, chromosomal aberrations and newer mutations, are the most clinically relevant prognostic markers. Chemoimmunotherapy (CIT) has become the treatment of choice for young and fit CLL patients. Various inhibitors of BCR signaling pathways and immunomodulatory drugs have shown efficacy in clinical trials. The most recent advance is the use of chimeric antigen receptor therapy (CAR) based on autologous T-lymphocytes. Nevertheless, CLL remains an incurable disease today. Coordinated developments between laboratory and clinic will hopefully translate into a cure for CLL. This short review focuses on advances in prognostication and therapy in CLL.
Income Differences in Perceived Neighborhood Environment Characteristics among African American Women
Authors: Adamus-Leach Heather J. , Mama Scherezade K. , O'Connor Daniel P. , Lee Rebecca E.
Published: November 2012

Perceptions of neighborhood attributes for physical activity may be influenced by individual level income. This study examined differences in perceptions of neighborhood attributes for walking and bicycling in high and low income African American women. African American women (n = 388) aged 20-65 years completed the International Physical Activity Prevalence Study's Environmental Survey Module. Independent t-tests determined differences in perceptions of neighborhood attributes by income group. Principal component factor analysis explored differences in factor structure for survey items. Low income African American women perceived their neighborhood as being less safe with regard to crime and traffic, having fewer free recreational opportunities, and having more public transportation stops nearby. Survey items weighed differently on each factor between income groups. Household income should be taken into consideration when interpreting perceptions of neighborhood for physical activity in African American women.
Automated measurement of diatom size
Authors: Spaulding Sarah A. , Jewson David H. , Bixby Rebecca J. , Nelson Harry , McKnight Diane M.
Published: November 2012

Size analysis of diatom populations has not been widely considered, but it is a potentially powerful tool for understanding diatom life histories, population dynamics, and phylogenetic relationships. However, measuring cell dimensions on a light microscope is a time‐consuming process. An alternative technique has been developed using digital flow cytometry on a FlowCAM® (Fluid Imaging Technologies) to capture hundreds, or even thousands, of images of a chosen taxon from a single sample in a matter of minutes. Up to 30 morphological measures may be quantified through post‐processing of the high resolution images. We evaluated FlowCAM size measurements, comparing them against measurements from a light microscope. We found good agreement between measurement of apical cell length in species with elongated, straight valves, including small Achnanthidium minutissimum (11‐21 µm) and large Didymosphenia geminata (87–137 µm) forms. However, a taxon with curved cells, Hannaea baicalensis (37–96 µm), showed differences of ~ 4 µm between the two methods. Discrepancies appear to be influenced by the choice of feret or geodesic measurement for asymmetric cells. We describe the operating conditions necessary for analysis of size distributions and present suggestions for optimal instrument conditions for size analysis of diatom samples using the FlowCAM. The increased speed of data acquisition through use of imaging flow cytometers like the FlowCAM is an essential step for advancing studies of diatom populations.
Detection and quantification of β‐methylamino‐L‐alanine in aquatic invertebrates
Authors: Christensen Stephanie J. , Hemscheidt Thomas K. , Trapido‐Rosenthal Henry , Laws Edward A. , Bidigare Robert R.
Published: November 2012

β‐N‐methylamino‐L‐alanine (BMAA) is an excitotoxic neurotoxin that has been implicated in the etiology of Amyotrophic Lateral Sclerosis‐Parkinsonism‐Dementia Complex in the South Pacific island of Guam. BMAA has been reported to be present in a wide range of cyanobacteria taxa and aquatic invertebrates. However, there are large uncertainties in the human health risks associated with BMAA exposure because of the analytical challenges associated with the detection and quantification of BMAA. Here we describe an improved liquid chromatography‐mass spectrometry/mass spectrometry (LC‐MS/MS) method for the analysis of BMAA in aquatic invertebrate sample matrices, and present initial findings for oysters and blue crabs collected in the southeastern United States. The LC‐MS/MS method is linear over a wide range of BMAA concentrations (0.4−153.2 pg µL−1, r2 = 0.997), and analytically precise, with a relative standard deviation (RSD) of 2.4%. The on‐column limit of detection (LoD) and limit of quantification (LoQ) values for this method were determined to be 5 pg (0.2 pg µL−1) and 17 pg (0.8 pg µL−1), respectively. We observed a weak ion enhancement effect of ~10% in a mollusk matrix that tested negative for BMAA. Analyte recovery for the method averaged 92% (8% RSD). BMAA concentrations for oysters and blue crabs ranged from 5 to 47 µg g−1 dry weight sample and are substantially lower than the concentrations reported previously with a nonspecific BMAA method that was based on liquid chromatography‐fluorescence detection (LC‐FL). We conclude that BMAA analysis via LC‐MS/MS methodologies is absolutely necessary for obtaining reliable data.
Crop harvest in Denmark and Central Europe contributes to the local load of airborne Alternaria spore concentrations in Copenhagen
Authors: Skjøth C. A. , Sommer J. , Frederiksen L. , Gosewinkel Karlson U.
Published: November 2012

Abstract. This study examines the hypothesis that Danish agricultural areas are the main source of airborne Alternaria spores in Copenhagen, Denmark. We suggest that the contribution to the overall load is mainly local or regional, but with intermittent long distance transport (LDT) from more remote agricultural areas. This hypothesis is supported by investigating a 10 yr bi-hourly record of Alternaria spores in the air from Copenhagen. This record shows 232 clinically relevant episodes (daily average spore concentration above 100 m−3) with a distinct daily profile. The data analysis also revealed potential LDT episodes almost every year. A source map and analysis of atmospheric transport suggest that LDT always originates from the main agricultural areas in Central Europe. A dedicated emission study in cereal crops under harvest during 2010 also supports our hypothesis. The emission study showed that although the fields had been treated against fungal infections, harvesting still produced large amounts of airborne fungal spores. It is likely that such harvesting periods can cause clinically relevant levels of fungal spores in the atmosphere. Our findings suggest that crop harvest in Central Europe causes episodes of high airborne Alternaria spore concentrations in Copenhagen as well as other urban areas in this region. It is likely that such episodes could be simulated using atmospheric transport models.
A novel source of atmospheric H2: abiotic degradation of organic material
Authors: Lee H. , Rahn T. , Throop H. L.
Published: November 2012

Abstract. Molecular hydrogen (H2) plays an important role in atmospheric chemistry by competing for reactions with the hydroxyl radical (OH·) and contributing to the production of H2O in the stratosphere, indirectly influencing stratospheric ozone concentrations. The dominant pathway for loss of H2 from the atmosphere is via microbially-mediated soil uptake, although the magnitude of this loss is still regarded as highly uncertain. Recent studies have shown that abiotic processes such as photochemically mediated degradation (photodegradation) of organic material result in direct emissions of carbon (C) and nitrogen (N)-based trace gases as well as H2. This H2 production has important implications on source-sink dynamics of H2 at the soil-atmosphere interface and thus it is important to quantify its variability over a range of plant types and materials. Here, we show laboratory observations of H2 production and its temperature dependence during abiotic degradation of four plant litter types as well as pure cellulose and high lignin content woody material. A greater amount of H2 was produced in the absence of solar radiation than from photodegradation alone, verifying that low temperature thermal degradation of plant litter is a source of H2. In addition, we measured a significant release of H2 both in the presence and absence of O2. Our results suggest that abiotic release of H2 during organic matter degradation is ubiquitous in arid ecosystems and may also occur in other terrestrial ecosystems. We propose that because these processes occur at the soil-atmosphere interface, they provide a previously unrecognized proximal source of H2 for microbial uptake and confound interpretation of direct measurements of atmospheric uptake that are important for constraining the global H2 budget.
Quantifying different sources of uncertainty in hydrological projections in an Alpine watershed
Authors: Dobler C. , Hagemann S. , Wilby R. L. , Stötter J.
Published: November 2012

Abstract. Many studies have investigated potential climate change impacts on regional hydrology; less attention has been given to the components of uncertainty that affect these scenarios. This study quantifies uncertainties resulting from (i) General Circulation Models (GCMs), (ii) Regional Climate Models (RCMs), (iii) bias-correction of RCMs, and (iv) hydrological model parameterization using a multi-model framework. This consists of three GCMs, three RCMs, three bias-correction techniques, and sets of hydrological model parameters. The study is performed for the Lech watershed (~ 1000 km2), located in the Northern Limestone Alps, Austria. Bias-corrected climate data are used to drive the hydrological model HQsim to simulate runoff under present (1971–2000) and future (2070–2099) climate conditions. Hydrological model parameter uncertainty is assessed by Monte Carlo sampling. The model chain is found to perform well under present climate conditions. However, hydrological projections are associated with high uncertainty, mainly due to the choice of GCM and RCM. Uncertainty due to bias-correction is found to have greatest influence on projections of extreme river flows, and the choice of method(s) is an important consideration in snowmelt systems. Overall, hydrological model parameterization is least important. The study also demonstrates how an improved understanding of the physical processes governing future river flows can help focus attention on the scientifically tractable elements of the uncertainty.
Adherence in HIV‐positive patients treated with single‐tablet regimens and multi‐pill regimens: findings from the COMPACT study
Authors: Antinori A , Angeletti C , Ammassari A , Sangiorgi D , Giannetti A , Buda S , Girardi E , Degli Esposti L
Published: November 2012

The use of Combination AntiRetroviral Therapy (cART) has decreased the morbidity and mortality of patients infected with HIV. However, adherence to cART remains crucial to prevent virological failure and disease progression. The aim of this study was to assess adherence to treatment among patients treated with Single Tablet Regimen (STR) or with multi‐pill regimens based on Protease Inhibitors (PI), Non‐Nucleoside Reverse‐Transcriptase Inhibitors (NNRTI), or raltegravir (RAL). An observational retrospective cohort analysis based on administrative and clinical databases was conducted at the National Institute for Infectious Diseases (Rome, Italy). HIV‐positive patients treated with a cART between Jan 1st, 2008–Dec 31st, 2010 were included. Patients were followed‐up for one year since the first prescription during the inclusion period or up to death or switch of at least one drug of the regimen. Adherence and selective non‐adherence (days without backbone or 3rd drug) were calculated using pharmacy refill compliance [1]. cART regimens were classified based on number of daily pills (STR vs multi‐pill regimen) and on type of third drug. Viral Load (VL) and CD4 cell counts at the end of the follow‐up were evaluated. A total of 1,604 patients were analyzed, 70.0% male, age 45.0±8.7, 14.3% newly treated. Patients on STR were 159 (9.9%), PI 878 (54.7%), NNRTI 523 (32.6%), RAL 44 (2.7%). Presence of at least one AIDS‐defining conditions (according to Centers for Disease Control classification) was 30% in the STR group, 34% PI, 26% NNRTI, 34% RAL (p=n.s.). Adherence was 80.4±14.7% for STR, 71.8±21.8% PI, 77.1±20.3% NNRTI, 74.0±22.4% RAL. Selective non‐adherence was 5.5% (18 days) PI, 2.8% (8 days) NNRTI, 12.5% (43 days) RAL (Figure 1). At the end of the follow‐up, VL/CD4 values were available among 709 patients (44%); CD4 count >500 cell/mm3 was observed among 61% of patients on STR, 44% PI, 48% NNRTI, 42% RAL and VL < 50 copies/ml was observed among 96% of patients on STR, 78% PI, 88% NNRTI, 87% RAL. Interruptions in cART refill remain a relevant problem across all cART regimens. Patients on STR displayed a higher adherence rate compared to multi‐pill regimes (PI, NNRTI, and RAL), primarily due to lack of selective non‐adherence. Patients on STR experienced also higher rates of VL < 50 and CD4 > 500. The use of an STR regimen appears an effective therapeutic option to avoid selective non‐adherence and, consequently, to prevent virological failure and disease progression.

Non‐adherence to cART regimens.

image
Among once‐daily regimens, single tablet regimens (STRs) are associated with better adherence
Authors: Murri R , Fregosi S , Bortolussi P , Marcotullio S , Maggiolo F
Published: November 2012

Previous published evidences showed that taking HAART once‐daily (OD) is associated to better adherence when compared to BID or TID regimens. However, no further studies investigated whether, among OD regimens, adherence levels can be differently influenced. Aim of the study was to evaluate levels of self‐reported adherence in HIV+ people according to type of HAART dosing (STR, OD with more than one pill or BID). To limit reporting biases, the study was performed in five different non‐clinic settings covering North and Central Italy. A total of 230 patients on stable HAART were asked to complete a semi‐structured, anonymous questionnaire reporting their attitude toward HAART, their adherence and the acceptability of their regimen. Self‐perception of adherence was also investigated with a single item for comparison with real adherence behavior. Most of the subjects were males (66%) with a mean age of 46 years, with higher education level (72%) and a long history of HIV infection (mean 13.6 years). 17% of patients were on a first‐line regimen. 21% reported to miss at least one dose during the past week (STR: 6%; OD >1 pill 23% and BID 21%; p<0.05). People taking STR and BID tend to report less discontinuations (all the drug of the day for at least 3 times in a month) compared to OD>1 pill (6 and 4% vs 11%). People taking therapies other than HAART reported similar adherence levels of people taking only HAART, even when stratified for dosing groups. Even people judging their adherence as ‘optimal’ or ‘very good’, 10 and 17% respectively, reported having missed a dose during the last week. At stepwise regression model, optimal adherence was correlated to being male (OR: 2.38; 95% CI: 1.19–4.74), younger (OR: 3.04; 95% CI: 1.01–9.13) and with a shorter HIV infection (OR: 3.58; 95% CI: 1.04–12.38). People taking simpler once‐daily STR tend to report better adherence than people taking OD>1 pill or BID. Perception of optimal adherence is largely variable among HIV‐infected people taking HAART, although only a minority of subjects showing less than perfect adherence do judge their behavior as ‘optimal’.
CD4 count evolution of HIV‐infected patients in follow‐up as an indicator of quality of care
Authors: Sasse A , Van Beckhoven D ,   for the Belgian Research AIDS and HIV Consortium (BREACH)
Published: November 2012

Objective

To study the evolution of CD4 count of HIV‐infected patients in follow‐up as an indicator of quality of care.

Methods

Adult patients newly diagnosed with HIV in 2007 who entered in care in the AIDS Reference Centres (ARC) and remained in care for at least one year were studied until end 2009. Optimal CD4 evolution was defined as having a CD4 count above 350 cells/mm3 after 1 year in HIV care, or an increasing rate exceeding 50 cells/mm3 per year, and this regardless of antiviral therapy. The proportion of patients with optimal CD4 evolution was measured and factors associated with outcome were identified by logistic regression.

Results

482 patients were included. Median age was 37 years, 31.1% were females, 51.7% Belgians, 32.2% from Sub‐Saharan Africa, 50.5% heterosexual, 48.7% MSM. 59.5% had a CD4 count above 350 at entry in care, 11.2% did not have a regular retention in care (at least 1 consultation/6‐month period). 401 (83.2%) patients had an optimal CD4 evolution after 1 year in care. 60.5% of patients with non‐optimal evolution had a CD4 count below 350 at entry in care. Although the proportion of female sex, heterosexual transmission, Sub‐Saharan nationality and low retention in care was higher in the non‐optimal CD4 evolution group compared to the optimal group, none of these characteristics showed a significant association with non‐optimal CD4 count evolution.

Conclusion

83.2% of patients had an optimal CD4 evolution after at least 1 year in HIV care. This indicator, analysed together with indicators of entry and retention in care, could contribute to a better monitoring of the HIV epidemic and to identify more precisely the steps in care system that could be improved. These indicators should be fully integrated in HIV surveillance.

Characteristics associated with non optimal CD4 evolution among patients in care

Optimal CD4 evolution
Non‐optimal CD4 evolution
OR (95% CI)
Adjusted OR (95% CI)

Gender (N, %)

Male
281 (70.1)
51 (63.0)
1
1

Female
120 (29.9)
30 (37.0)
1.38 (0.84–2.27)
0.89 (0.41–1.91)

Age at diagnosis (N, %)

<40 yrs
252 (62.8)
51 (63.0)
1
1

≥40 yrs
149 (37.2)
30 (37.0)
0.99 (0.61–1.63)
1.06 (0.60–1.98)

Way of transmission (N, %)

Heterosexual
162 (49.4)
37 (56.1)
1
1

MSM
163 (49.7)
29 (43.9)
0.78 (0.46–1.33)
0.85 (0.40–1.80)

IDU
3 (0.9)
0 (0.0)
/

Nationality (N, %)

Belgian
177 (52.8)
32 (46.4)
1
1

SSA
103 (30.8)
27 (39.1)
1.45 (0.82–2.56)
1.37 (0.62–3.01)

European
39 (11.6)
4 (5.8)
0.57 (0.19–1.70)
0.57 (0.19–1.73)

Other
16 (4.8)
6 (8.7)
2.07 (0.75–1.70)
1.74 (0.57–5.30)

Retention in care (N, %)

≥1 consult./period
359 (89.5)
69 (85.2)
1
1

<1 consult./period
42 (10.5)
12 (14.8)
1.49 (0.74–2.97)
1.45 (0.68–3.12)
Single‐tablet regimens (STRs) enhance patients’ acceptability of HAART
Authors: Maggiolo F , Fregosi S , Bortolussi P , Marcotullio S , Murri R
Published: November 2012

Patients’ acceptability of HAART is a subjective variable that may deeply influence therapeutic outcome. The feeling of the patient may alter adherence and lead to virologic failure. Acceptability may depend on various variables often difficulty evaluated by the care‐giver. In a clinical setting the evaluation of acceptability is difficult, too, as patients may feel a judgement and be less sincere. Aim of this study was to asses adherence and acceptability of HAART. To limit reporting biases, the study was performed in five different non‐clinic settings covering North and Central Italy. A total of 230 patients on stable HAART were asked to complete a semi‐structured, anonymous questionnaire reporting their attitude toward HAART, their adherence and the acceptability of their regimen. In these notes we focus on this last patient‐oriented outcome. Most of the subjects were males (66%) with a mean age of 46 years, with higher education level (72%) and a long history of HIV infection (mean 13.6 years). Consequently only 17% of patients were on a first‐line regimen. Patients reporting a high or very high acceptability of HAART were 60% compared to a 31% reporting a fair grade of satisfaction and a 9% indicating low or null acceptability. However the type of the regimen significantly influenced patients’ acceptability. Single‐tablet regimens (STRs), OD regimens with more than one tablet/day or BID regimens were scored as highly acceptable in 84%; 61%; and 53% of cases, respectively (P < 0.0001) (Figure). Statistical significance was retained when the dosing schedule was entered in a multivariate logistic model. When the analysis was restricted to experienced patients 62% of them were currently on a regimen based on a reduced number of pills compared to the previous one. Patients scored the previous regimen as more difficult to comply with in 72% of cases; as difficult in 22% and less difficult in 6%. The eventuality of AEs (40%); respect of timing of pill intake (39%) and number of pills (27%) were the major reasons of patients’ low acceptability of HAART. High acceptability is one of the winning characteristics of a regimen, favoring long‐term adherence, durability and efficacy. Although highly subjective, acceptability may be positively influenced by characteristics of the HAART regimen such as simplicity. According to our results, STRs show a higher acceptability compared to more complex regimens.

Patient reported acceptability for thier current HAART regimen.

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Self‐reported adherence supports patient preference for the single tablet regimen (STR) in the current cART era
Authors: Sterrantino G , Santoro L , Trotta M , Antinori A , Bartolozzi D , Zaccarelli M
Published: November 2012

Objective

To analyze self‐reported adherence to antiretroviral regimens containing ritonavir‐boosted protease inhibitors, non‐nucleoside reverse transcriptase inhibitors (NNRTI), raltegravir, and maraviroc.

Methods

Overall, 372 consecutive subjects attending a reference center for HIV treatment in Florence, Italy, were enrolled in the study, from December 2010 to January 2012 (mean age 48 years). A self‐report questionnaire was filled in. Patients were defined as “non‐adherent” if reporting one of the following criteria:<90% of pills taken in the last month, ≥1 missed dose in the last week, spontaneous treatment interruptions reported, or refill problems in the last 3 months. Gender, age, CD4, HIV‐RNA, years of therapy, and type of antiretroviral regimen were analyzed with respect to adherence.

Results

At the time of the questionnaire, 89.8% of patients had <50 copies/mL HIV‐RNA and 14.2% were on their first combined antiretroviral therapy. 57% of patients were prescribed a regimen containing ritonavir boosted protease inhibitors (boosted PI), 41.7% NNRTI, 17.2% raltegravir, and 4.8% maraviroc; 49.5% of the subjects were on bis‐in‐die regimens, while 50.5% were on once‐daily regimens, with 23.1% of these on the single tablet regimen (STR): tenofovir/emtricitabine/efavirenz. The non‐adherence proportion was lower in NNRTI than in boosted‐PI treatments (19.4% vs 30.2%), and even lower in STR patients (17.4%). In multivariable logistic regression, patients with the NNRTI regimen (OR: 0.56, 95% CI: 0.34–0.94) and the STR (OR: 0.45, 95% CI: 0.22–0.92) reported lower non‐adherence. Efavirenz regimens were also associated with lower non‐adherence (OR: 0.42, 95% CI: 0.21–0.83), while atazanavir/ritonavir regimens were associated with higher non‐adherence. No other relation to specific antiretroviral drugs was found. A higher CD4 count, lower HIV‐RNA, and older age were also found to be associated with lower non‐adherence, while a longer time on combined antiretroviral therapy was related to higher non‐adherence.

Conclusion

In conclusion, older age, higher CD4 cell counts, lower HIV‐RNA viral loads, and the use of STR are all related to lower non‐adherence. In particular, the use of STR maintains an advantage in improving adherence with respect to other cARTs, even with the availability of new, well‐tolerated antiretroviral drugs and drug classes in recent years.
Adherence and neurocognitive screening in Romanian HIV patients
Authors: Arbune M
Published: November 2012

Background

Adherence is critical for the effectiveness of antiretroviral HIV therapy (ART), accordingly decreasing the opportunistic diseases and increasing the quality of life. Neurocognitive disorders (NCD) are still frequent in ART era and could impair the adherence, but how ethical is to refer ART in patients with NCD?

Objective

To assess the relation between NCD and adherence in HIV Romanian patients.

Material and methods

Cross‐sectional screening study on 151 patients under ART, no drug users, from HIV Clinic ‐ Galati, assessed by HIV‐Associated Dementia Scale (HDS), Hospital Anxiety and Depression Scale (HADS) [1], ART CNS‐effectiveness Letendre scores [2] and adherence assessment questionnaire CNLAS‐ Romania. Normal values: HDS >10; anxiety/ depression <8. Statistical analysis performed: Chi‐square test and Mann‐Whitney test, with 5% significance level.

Results

Characteristics of the patients: median age 22 [20; 56] years old; sex ratio F/M 1.17; median educational level 8 [0; >12] years; HBV co‐infection 27.8%; AIDS stage 85.3%; current median CD4 526/mm3 [8; 1605] and 65% undetectable HIV‐RNA levels. 49.6% (75/151) patients attain HDS scores <10 and imply probable NCD. Scores below 8 for anxiety are more frequent than for depression: 24% vs 13%. The median ART CNS penetration score is 8 [5; 12]. Adherence is considered for 66% patients and is correlating with CD4 number (p=0.001), educational level >4 years (p=0.001; OR=4.2), HDS >10 (p=0.01; OR=2.4) and ART‐CNS penetration score >7 (p=0.023; OR=2.4). Low HDS are influenced by old age (p=0.003), depression (p=0.02) and ART‐CNS penetration scores <7 (p=0.01). Anxiety is related neither with adherence nor with NCD by HDS, but females are obvious anxious than males (p<0.001).

Conclusions

Basic educational level is sufficient for developing ART adherence. High scores of HDS screening should be predictors for ART adherence. Referring ART as well to patients with low HDS scores is rational and ethical, if joint actions of effective ART‐CNS regimens and depression improvement strategy are considered.
Efficacy assessment of the implemented strategies to improve loss to follow‐up in recently diagnosed HIV patients
Authors: Fridman V , Bello N , Lasala M
Published: November 2012

Purpose of the study

The aim of the present study is to evaluate the strategies performed to decrease the loss to follow up in recently diagnosed HIV patients.

Method

We reviewed the clinical charts of the recently diagnosed adult (>18 y/o) HIV patients who presented for the first time in our HIV clinic between 1/Jan/2009 and 30/Nov/2010. Among the patients who were newly diagnosed with HIV infection, we identified those who attended our clinic only once. Since January 2009, we implemented new strategies: those patients who were diagnosed with HIV infection were assigned an early appointment with an attending; those patients who did not attend the appointment were called to reassign another appointment; clinic hours were increased, another attending joined the team and the matters the patients had to deal with were reduced. The results obtained with regard to loss to follow up in these patients were compared with previous results, before January 2009, to assess the effectiveness of these measures.

Summary of the results

247 patients attended the clinic for the first time, 43 (17.4%) of them attended the clinic only once. Comparing with the 45‐month period before the implementation of these strategies in which 256 patients attend the clinic and 135 (52.7%) attended the clinic only once, loss to follow up was improved (P=0.0000 [OR 0.19, 95% CI 0.12–0.29]). No statistically significant differences were found between both groups regarding age, gender, nationality, employment status, presence of family/partner at home or access to health insurance.

Patients who attended the clinic for the first time between Jan 2005–Sept 2008, n=256
Patients who attended the clinic for the first time between Jan 2009–Nov 2010, n=247

Male/female
186/70
182/65
P=0.79, OR 1.05 (95% CI 0.70–1.59)

Argentinian
218
199
P=0.17, OR 0.13 (95% CI 0.84–2.26)

Health insurance
107
94
P=0.39, OR 0.86 (95% CI 0.59–1.24)

Tertiary/university degree
74
71
P=0.96, OR 1.01 (95% CI 0.67–1.15)

Employed
182
192
P=0.08, OR 1.42 (95% CI 0.93–2.17)

Living alone
52
63
P=0.16, OR 1.34 (95% CI 0.87–2.08)

Loss to follow up
135/(52.7%)
43/(17.4%)
P=0.0000, OR 0.19 (95% CI 0.12–0.29)

Conclusions

Although the small sample size, the implemented measures decreased the lost to follow up in our clinic. This study emphasises the need to continue reinforcing engagement with clinical care in the newly diagnosed HIV patients.
A dynamic assessment of medication‐taking behavior during pregnancy and postpartum: should cART adherence be reinforced during postpartum?
Authors: Michel O , Gertsch A , Locatelli I , Cavassini M , Rickenbach M , Bugnon O , Schneider M
Published: November 2012

This study compared adherence (persistence and execution) during pregnancy and postpartum in HIV‐positive women having taken part in the adherence‐enhancing program of the Community Pharmacy of the Department of Ambulatory Care and Community Medicine in Lausanne between 2004 and 2012. This interdisciplinary program combined electronic drug monitoring and semi‐structured, repeated motivational interviews. This was a retrospective, observational study. Observation period spread over from first adherence visit after last menstruation until 6 months after childbirth. Medication‐taking was recorded by electronic drug monitoring. Socio‐demographic and delivery data were collected from Swiss HIV Cohort database. Adherence data, barriers and facilitators were collected from pharmacy database. Electronic data were reconciled with pill‐count and interview notes in order to include reported pocket‐doses. Execution was analyzed over 3‐day periods by a mixed effect logistic model, separating time before and after childbirth. This model allowed us to estimate different time slopes for both periods and to show a sudden fall associated with childbirth. Twenty‐five pregnant women were included. Median age was 29 (IQR: 26.5, 32.0), women were in majority black (n = 17,68%) and took a cART combining protease and nucleoside reverse transcriptase inhibitors (n = 24,96%). Eleven women (44%) were ART‐naïve at the beginning of pregnancy. Twenty women (80%) were included in the program because of pregnancy. Women were included at all stages of pregnancy. Six women (24%) stopped the program during pregnancy, 3 (12%) at delivery, 4 (16%) during postpartum and 12 (48%) stayed in program at the end of observation time. Median number of visits was 4 (3.0, 6.3) during pregnancy and 3 (0.8, 6.0) during postpartum. Execution was continuously high during pregnancy, low at beginning of postpartum and increased gradually during the 6 months of postpartum.

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Major barriers to adherence were medication adverse events and difficulties in daily routine. Facilitators were motivation for promoting child‐health and social support. The dramatic drop and very slow increase in cART adherence during postpartum might result in viral rebound and drug resistance. Although much attention is devoted to pregnant women, interdisciplinary care should also be provided to women in the community during first trimester of postpartum to support them in sustaining cART adherence.
Late gadolinium enhancement and subclinical cardiac dysfunction on cardiac MRI in asymptomatic HIV‐positive men
Authors: Loy A , Morgan R , O'Dea S , Takacs E , Daly C , Mulcahy F
Published: November 2012

Background

HIV is associated with an increased risk of cardiovascular disease (CVD) and related clinical events. While traditional risk factors play an important role in the pathology of cardiovascular disease, HIV infection and its sequelae of immune activation and inflammation may have significant effects on the myocardium before becoming clinically evident. Cardiac MRI (CMR) can be used to detect the pattern of these subclinical changes. This will lead to a better understanding of risk factors contributing to cardiovascular disease prior to it becoming clinically significant in HIV‐positive patients.

Methods

Prospective cohort study of 127 asymptomatic HIV‐positive men on ART compared to 35 matched controls. Baseline demographics, HIV parameters, 12‐lead ECG, routine biochemistry, and traditional cardiovascular risk factors were recorded. Images were acquired on a 3T Achieva Philips MRI scanner with 5 channel phase array cardiac coil and weight‐based IV gadolinium was given at 0.15 mmol/kg dose with post‐contrast inversion recovery imaging after 10 minutes.

Results

6/127 (4.7%) of asymptomatic HIV‐positive men had late gadolinium enhancement (LGE) on MRI verses 1/35 (2.9%) in the control group. In 3/6 (50%) of cases this was in a classical infarction pattern with subendocardial involvement. 3/6 (50%) were consistent with prior myocarditis. There was no significant difference in mean LVEF (66.93% vs 65.18%), LVMI (60.05g/m2 vs 55.94g/m2) or posterolateral wall thickness (8.28 mm and 8.16 mm) between cases and controls respectively. There was significantly more diastolic dysfunction, E:A ratio < 1, found in the HIV‐positive group, 18% vs 7% of controls (p = 0.037). Framingham risk did not predict either of these outcomes.

Conclusions

There is an increased incidence of LGE detected on CMR in this asymptomatic HIV‐positive cohort. Two distinct pathological processes were identifed as causing these changes, myocardial infarction and myocarditis. These findings were independent of traditional cardiac risk factors, duration of HIV infection and ART therapy. Sub clinical cardiac dysfunction may be underreported in other cardiac evaluation studies. The true impact of other potential risk factors may also be underestimated, highlighting the need for the development of more complex prediction models.