Adherence to and effectiveness of highly active antiretroviral treatment for HIV infection: assessing the bidirectional relationship.

BACKGROUND: It is well established that high adherence to HIV-infected patients on highly active antiretroviral treatment (HAART) is a major determinant of virological and immunologic success. Furthermore, psychosocial research has identified a wide range of adherence factors including patients' subjective beliefs about the effectiveness of HAART. Current statistical approaches, mainly based on the separate identification either of factors associated with treatment effectiveness or of those associated with adherence, fail to properly explore the true relationship between adherence and treatment effectiveness. Adherence behavior may be influenced not only by perceived benefits-which are usually the focus of related studies-but also by objective treatment benefits reflected in biological outcomes. METHODS: Our objective was to assess the bidirectional relationship between adherence and response to treatment among patients enrolled in the ANRS CO8 APROCO-COPILOTE study. We compared a conventional statistical approach based on the separate estimations of an adherence and an effectiveness equation to an econometric approach using a 2-equation simultaneous system based on the same 2 equations. RESULTS: Our results highlight a reciprocal relationship between adherence and treatment effectiveness. After controlling for endogeneity, adherence was positively associated with treatment effectiveness. Furthermore, CD4 count gain after baseline was found to have a positive significant effect on adherence at each observation period. This immunologic parameter was not significant when the adherence equation was estimated separately. In the 2-equation model, the covariances between disturbances of both equations were found to be significant, thus confirming the statistical appropriacy of studying adherence and treatment effectiveness jointly. CONCLUSIONS: Our results, which suggest that positive biological results arising as a result of high adherence levels, in turn reinforce continued adherence and strengthen the argument that patients who do not experience rapid improvement in their immunologic and clinical statuses after HAART initiation should be prioritized when developing adherence support interventions. Furthermore, they invalidate the hypothesis that HAART leads to "false reassurance" among HIV-infected patients.

Relationship between potassium fertilization and panicle blast severity in upland rice

The influence of K2O (0, 40, 80, 120 kg ha-1) at varying rates of N application (0, 30, 60 kg ha-1) at planting, on panicle blast (Pyricularia grisea (Cooke) Sacc.) was studied in a field experiment conducted during three consecutive years with the upland rice cultivar Douradão. Panicle blast severity decreased with increasing rates of potassium in the absence of nitrogen (N0). The relationship between panicle blast and K rates was quadratic at 30 kg ha-1 of nitrogen. Significant response to K fertilization was not obtained at 60 kg ha-1 of nitrogen in relation to panicle blast severity.

Dosage optimization of treatments using population pharmacokinetic modeling and simulation.

Pharmacokinetic variability in drug levels represent for some drugs a major determinant of treatment success, since sub-therapeutic concentrations might lead to toxic reactions, treatment discontinuation or inefficacy. This is true for most antiretroviral drugs, which exhibit high inter-patient variability in their pharmacokinetics that has been partially explained by some genetic and non-genetic factors. The population pharmacokinetic approach represents a very useful tool for the description of the dose-concentration relationship, the quantification of variability in the target population of patients and the identification of influencing factors. It can thus be used to make predictions and dosage adjustment optimization based on Bayesian therapeutic drug monitoring (TDM). This approach has been used to characterize the pharmacokinetics of nevirapine (NVP) in 137 HIV-positive patients followed within the frame of a TDM program. Among tested covariates, body weight, co-administration of a cytochrome (CYP) 3A4 inducer or boosted atazanavir as well as elevated aspartate transaminases showed an effect on NVP elimination. In addition, genetic polymorphism in the CYP2B6 was associated with reduced NVP clearance. Altogether, these factors could explain 26% in NVP variability. Model-based simulations were used to compare the adequacy of different dosage regimens in relation to the therapeutic target associated with treatment efficacy. In conclusion, the population approach is very useful to characterize the pharmacokinetic profile of drugs in a population of interest. The quantification and the identification of the sources of variability is a rational approach to making optimal dosage decision for certain drugs administered chronically.

Having a good relationship with their mother: a protective factor against sexual risk behavior among adolescent females?

STUDY OBJECTIVE: To assess whether having a good relationship with their mother was a protective factor against risky sexual behavior for female adolescents and whether it was independent of family structure. DESIGN: Cross-sectional survey of in-school adolescents aged 14-19 years. SETTING: Catalonia, in northeast Spain. PARTICIPANTS: A total of 3677 females divided according on whether they had a good (n=3335) or a bad (n=342) relationship with their mother. MAIN OUTCOME MEASURES: Rates of sexual activity and sexual behavior. RESULTS: Adolescents in the good relationship group were significantly younger, more likely to live in an intact family, to have a good relationship with their father and siblings, and to talk about sexuality and their partner with their mother. They were also less likely to have ever had sexual intercourse. Among those sexually experienced, they were significantly older at first intercourse and less likely to have multiple partners or a history of STI. After adjusting for potential confounders, females in the good relationship group were less likely to be sexually active and to have had multiple partners, independently of family structure. CONCLUSIONS: Having a good relationship with their mother is a protective factor against sexual intercourse and having multiple sexual partners independently of family structure. Communication between generations and having a good relationship with their father and siblings also play an important role.

Quantifying the weight of fingerprint evidence through the spatial relationship, directions and types of minutiae observed on fingermarks

This paper presents a statistical model for the quantification of the weight of fingerprint evidence. Contrarily to previous models (generative and score-based models), our model proposes to estimate the probability distributions of spatial relationships, directions and types of minutiae observed on fingerprints for any given fingermark. Our model is relying on an AFIS algorithm provided by 3M Cogent and on a dataset of more than 4,000,000 fingerprints to represent a sample from a relevant population of potential sources. The performance of our model was tested using several hundreds of minutiae configurations observed on a set of 565 fingermarks. In particular, the effects of various sub-populations of fingers (i.e., finger number, finger general pattern) on the expected evidential value of our test configurations were investigated. The performance of our model indicates that the spatial relationship between minutiae carries more evidential weight than their type or direction. Our results also indicate that the AFIS component of our model directly enables us to assign weight to fingerprint evidence without the need for the additional layer of complex statistical modeling involved by the estimation of the probability distributions of fingerprint features. In fact, it seems that the AFIS component is more sensitive to the sub-population effects than the other components of the model. Overall, the data generated during this research project contributes to support the idea that fingerprint evidence is a valuable forensic tool for the identification of individuals.

Relationship between imaging biomarkers, age, progression and symptom severity in Alzheimer's disease.

The early diagnostic value of glucose hypometabolism and atrophy as potential neuroimaging biomarkers of mild cognitive impairment (MCI) and Alzheimer's disease (AD) have been extensively explored using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (MRI). The vast majority of previous imaging studies neglected the effects of single factors, such as age, symptom severity or time to conversion in MCI thus limiting generalisability of results across studies. Here, we investigated the impact of these factors on metabolic and structural differences. FDG-PET and MRI data from AD patients (n = 80), MCI converters (n = 65) and MCI non-converters (n = 64) were compared to data of healthy subjects (n = 79). All patient groups were split into subgroups by age, time to conversion (for MCI), or symptom severity and compared to the control group. AD patients showed a strongly age-dependent pattern, with younger patients showing significantly more extensive reductions in gray matter volume and glucose utilisation. In the MCI converter group, the amount of glucose utilisation reduction was linked to the time to conversion but not to atrophy. Our findings indicate that FDG-PET might be more closely linked to future cognitive decline whilst MRI being more closely related to the current cognitive state reflects potentially irreversible damage.

The influence of tobacco consumption on the relationship between schizotypy and hemispheric asymmetry.

Tobacco use is positively associated with severity of symptoms along the schizophrenia spectrum. Accordingly it could be argued that neuropsychological performance, formerly thought to be modulated by schizotypy, is actually modulated by drug use or an interaction of drug use and schizotypy. We tested whether habitual cigarette smokers as compared to non-smokers would show a neuropsychological profile similar to that observed along the schizophrenia spectrum and, if so, whether smoking status or nicotine dependence would be more significant modulators of behavior than schizotypy. Because hemispheric dominance has been found to be attenuated along the schizophrenia spectrum, 40 right-handed male students (20 non-smokers) performed lateralized left- (lexical decisions) and right- (facial decision task) hemisphere dominant tasks. All individuals completed self-report measures of schizotypy and nicotine dependence. Schizotypy predicted laterality in addition to smoking status: While positive schizotypy (Unusual Experiences) was unrelated to hemispheric performance, Cognitive Disorganization predicted reduced left hemisphere dominant language functions. These latter findings suggest that Cognitive Disorganization should be regarded separately as a potentially important mediator of thought disorganization and language processing. Additionally, increasing nicotine dependence among smokers predicted a right hemisphere shift of function in both tasks that supports the role of the right hemisphere in compulsive/impulsive behavior.

Relationship between empty seed and genetic factors in European beech (Fagus sylvatica L.)

Abstract

Relationship between squamous cell carcinoma of the anterior two thirds of the tongue and removable denture use - a pioneer study in a Portuguese

The aim of the study was to determine whether there is any relationship between the presence of removable dentures and squamous cell carcinoma of the anterior two thirds of the tongue in a Portuguese population. A retrospective cross-sectional study was conducted on patients with a biopsy-proven diagnosis of squamous cell carcinoma of the tongue, who were seen and treated at the Department of Head and Neck Surgery of the Portuguese Institute of Oncology 'Francisco Gentil', Lisbon, Portugal, during a 3-year period. Several factors were examined: gender, use of removable dentures, age, location of the lesion, and alcohol and tobacco consumption. One hundred and six cases were selected from the initial 151 cases, with a male:female ratio of 3:1 and the lateral borders being the most commonly affected site. The prevalence in both genders was between the sixth and seventh decade of life. Men were more likely to consume alcohol and tobacco than women, and no relationship was observed between denture use and presence of carcinoma of the tongue. In light of the data obtained, it may be considered that female use of a denture plays an important role, but it cannot be identified as a remarkable etiologic factor.

The relationship between cognitive errors and interpersonal patterns in depressed women.

Individuals with depression process information in an overly negative or biased way (e.g., Henriques & Leitenberg, 2002) and demonstrate significant interpersonal dysfunction (e.g., Zlotnick, Kohn, Keitner, & Della Grotta, 2000). This study examined the relationship between cognitive errors (CEs) and interpersonal interactions in early psychotherapy sessions of 25 female patients with major depression. Transcripts were rated for CEs using the Cognitive Error Rating Scale (Drapeau, Perry, & Dunkley, 2008). Interpersonal patterns were assessed using the Structural Analysis of Social Behavior (Benjamin, 1974). Significant associations were found between CEs and markers of interpersonal functioning in selected contexts. The implications of these findings in bridging the gap between research and practice, enhancing treatment outcome, and improving therapist training are discussed. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Lipophilicity and its relationship with passive drug permeation.

In this review, we first summarize the structure and properties of biological membranes and the routes of passive drug transfer through physiological barriers. Lipophilicity is then introduced in terms of the intermolecular interactions it encodes. Finally, lipophilicity indices from isotropic solvent systems and from anisotropic membrane-like systems are discussed for their capacity to predict passive drug permeation across biological membranes such as the intestinal epithelium, the blood-brain barrier (BBB) or the skin. The broad evidence presented here shows that beyond the predictive power of lipophilicity parameters, the various intermolecular forces they encode allow a mechanistic interpretation of passive drug permeation.

On the relationship between performance-approach goals and cognitive performance : when the desire to outperform others becomes interfering

Cette thèse explore dans quelle mesure la poursuite d'un but de performance-approche (i.e., le désir de surpasser autrui et de démontrer ses compétences) favorise, ou au contraire endommage, la réussite et l'apprentissage-une question toujours largement débattue dans la littérature. Quatre études menées en laboratoire ont confirmé cette hypothèse et démontré que la poursuite du but de performance-approche amène les individus à diviser leur attention entre d'une part la réalisation de la tâche évaluée, et d'autre part la gestion de préoccupations liées à l'atteinte du but-ceci empêchant une concentration efficace sur les processus de résolution de la tâche. Dans une deuxième ligne de recherche, nous avons ensuite démontré que cette distraction est exacerbée chez les individus les plus performants et ayant le plus l'habitude de réussir, ceci dérivant d'une pression supplémentaire liée au souhait de maintenir le statut positif de « bon élève ». Enfin, notre troisième ligne de recherche a cherché à réconcilier ces résultats-pointant l'aspect distractif du but de performance-approche-avec le profil se dégageant des études longitudinales rapportées dans la littérature-associant ce but avec la réussite académique. Ainsi, nous avons mené une étude longitudinale testant si l'adoption du but de performance-approche en classe pourrait augmenter la mise en oeuvre de stratégies d'étude tactiquement dirigées vers la performance-favorisant une réussite optimale aux tests. Nos résultats ont apporté des éléments en faveur de cette hypothèse, mais uniquement chez les élèves de bas niveau. Ainsi, l'ensemble de nos résultats permet de mettre en lumière les processus cognitifs à l'oeuvre lors de la poursuite du but de performance-approche, ainsi que d'alimenter le débat concernant leur aspect bénéfique ou nuisible en contexte éducatif. -- In this dissertation, we propose to investigate whether the pursuit of performance-approach goals (i.e., the desire to outperform others and appear talented) facilitates or rather endangers achievement and learning-an issue that is still widely discussed in the achievement goal literature. Four experiments carried out in a laboratory setting have provided evidence that performance- approach goals create a divided-attention situation that leads cognitive resources to be divided between task processing and the activation of goal-attainment concerns-which jeopardizes full cognitive immersion in the task. Then, in a second research line, we found evidence that high- achievers (i.e., those individuals who are the most used to succeed) experience, under evaluative contexts, heightened pressure to excel at the task, deriving from concerns associated with the preservation of their "high-achiever" status. Finally, a third research line was designed to try to reconcile results stemming from our laboratory studies with the overall profile emerging from longitudinal research-which have consistently found performance-approach goals to be a positive predictor of students' test scores. We thus set up a longitudinal study so as to test whether students' adoption of performance-approach goals in a long-term classroom setting enhances the implementation of strategic study behaviors tactically directed toward goal-attainment, hence favoring test performance. Our findings brought support for this hypothesis, but only for low-achieving students. Taken together, our findings shed new light on the cognitive processes at play during the pursuit of performance-approach goals, and are likely to fuel the debate regarding whether performance-approach goals should be encouraged or not in educational settings.

Prevalence, awareness and control of diabetes in the Seychelles and relationship with excess body weight.

BACKGROUND: The evidence for a "diabesity" epidemic is accumulating worldwide but population-based data are still scarce in the African region. We assessed the prevalence, awareness and control of diabetes (DM) in the Seychelles, a rapidly developing country in the African region. We also examined the relationship between body mass index, fasting serum insulin and DM. METHODS: Examination survey in a sample representative of the entire population aged 25-64 of the Seychelles, attended by 1255 persons (participation rate of 80.2%). An oral glucose tolerance test (OGTT) was performed in individuals with fasting blood glucose between 5.6 and 6.9 mmol/l. Diabetes mellitus (DM), impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were defined along criteria of the ADA. Prevalence estimates were standardized for age. RESULTS: The prevalence of DM was 11.5% and 54% of persons with DM were aware of having DM. Less than a quarter of all diabetic persons under treatment were well controlled for glycemia (HbA1c), blood pressure or LDL-cholesterol. The prevalence of IGT and IFG were respectively 10.4% and 24.2%. The prevalence of excess weight (BMI > or = 25 kg/m2) and obesity (BMI > or = 30 kg/m2) was respectively 60.1% and 25.0%. Half of all DM cases in the population could be attributed to excess weight. CONCLUSION: We found a high prevalence of DM and pre-diabetes in a rapidly developing country in the African region. The strong association between overweight and DM emphasizes the importance of weight control measures to reduce the incidence of DM in the population. High rates of diabetic persons not aware of having DM in the population and insufficient cardiometabolic control among persons treated for DM stress the need for intensifying health care for diabetes.

Relationship between estrogen receptor alpha location and gene induction reveals the importance of downstream sites and cofactors.

BACKGROUND: To understand cancer-related modifications to transcriptional programs requires detailed knowledge about the activation of signal-transduction pathways and gene expression programs. To investigate the mechanisms of target gene regulation by human estrogen receptor alpha (hERalpha), we combine extensive location and expression datasets with genomic sequence analysis. In particular, we study the influence of patterns of DNA occupancy by hERalpha on expression phenotypes. RESULTS: We find that strong ChIP-chip sites co-localize with strong hERalpha consensus sites and detect nucleotide bias near hERalpha sites. The localization of ChIP-chip sites relative to annotated genes shows that weak sites are enriched near transcription start sites, while stronger sites show no positional bias. Assessing the relationship between binding configurations and expression phenotypes, we find binding sites downstream of the transcription start site (TSS) to be equally good or better predictors of hERalpha-mediated expression as upstream sites. The study of FOX and SP1 cofactor sites near hERalpha ChIP sites shows that induced genes frequently have FOX or SP1 sites. Finally we integrate these multiple datasets to define a high confidence set of primary hERalpha target genes. CONCLUSION: Our results support the model of long-range interactions of hERalpha with the promoter-bound cofactor SP1 residing at the promoter of hERalpha target genes. FOX motifs co-occur with hERalpha motifs along responsive genes. Importantly we show that the spatial arrangement of sites near the start sites and within the full transcript is important in determining response to estrogen signaling.