Self-reported alcohol consumption and its association with adherence and outcome of antiretroviral therapy in the Swiss HIV Cohort Study.

BACKGROUND: Alcohol consumption leading to morbidity and mortality affects HIV-infected individuals. Here, we aimed to study self-reported alcohol consumption and to determine its association with adherence to antiretroviral therapy (ART) and HIV surrogate markers. METHODS: Cross-sectional data on daily alcohol consumption from August 2005 to August 2007 were analysed and categorized according to the World Health Organization definition (light, moderate or severe health risk). Multivariate logistic regression models and Pearson's chi(2) statistics were used to test the influence of alcohol use on endpoints. RESULTS: Of 6,323 individuals, 52.3% consumed alcohol less than once a week in the past 6 months. Alcohol intake was deemed light in 39.9%, moderate in 5.0% and severe in 2.8%. Higher alcohol consumption was significantly associated with older age, less education, injection drug use, being in a drug maintenance programme, psychiatric treatment, hepatitis C virus coinfection and with a longer time since diagnosis of HIV. Lower alcohol consumption was found in males, non-Caucasians, individuals currently on ART and those with more ART experience. In patients on ART (n=4,519), missed doses and alcohol consumption were positively correlated (P<0.001). Severe alcohol consumers, who were pretreated with ART, were more often off treatment despite having CD4+ T-cell count <200 cells/microl; however, severe alcohol consumption per se did not delay starting ART. In treated individuals, alcohol consumption was not associated with worse HIV surrogate markers. CONCLUSIONS: Higher alcohol consumption in HIV-infected individuals was associated with several psychosocial and demographic factors, non-adherence to ART and, in pretreated individuals, being off treatment despite low CD4+ T-cell counts.

Magnetic pill tracking : a novel non-invasive tool for investigation of human digestive motility

RESUME Les améliorations méthodologiques des dernières décennies ont permis une meilleure compréhension de la motilité gastro-intestinale. Il manque toutefois une méthode qui permette de suivre la progression du chyme le long du tube gastro-intestinal. Pour permettre l'étude de la motilité de tout le tractus digestif humain, une nouvelle technique, peu invasive, a été élaborée au Département de Physiologie, en collaboration avec l'EPFL. Appelée "Magnet Tracking", la technique est basée sur la détection du champ magnétique généré par des matériaux ferromagnétiques avalés. A cet usage, une pilule magnétique, une matrice de capteurs et un logiciel ont été développés. L'objet de ce travail est de démontrer la faisabilité d'un examen de la motilité gastro-intestinale chez l'Homme par cette méthode. L'aimant est un cylindre (ø 6x7 mm, 0.2 cm3) protégé par une gaine de silicone. Le système de mesure est constitué d'une matrice de 4x4 capteurs et d'un ordinateur portable. Les capteurs fonctionnent sur l'effet Hall. Grâce à l'interface informatique, l'évolution de la position de l'aimant est suivie en temps réel à travers tout le tractus digestif. Sa position est exprimée en fonction du temps ou reproduite en 3-D sous forme d'une trajectoire. Différents programmes ont été crées pour analyser la dynamique des mouvements de l'aimant et caractériser la motilité digestive. Dix jeunes volontaires en bonne santé ont participé à l'étude. L'aimant a été avalé après une nuit de jeûne et son séjour intra digestif suivi pendant 2 jours consécutifs. Le temps moyen de mesure était de 34 heures. Chaque sujet a été examiné une fois sauf un qui a répété sept fois l'expérience. Les sujets restaient en décubitus dorsal, tranquilles et pouvaient interrompre la mesure s'ils le désiraient. Ils sont restés à jeûne le premier jour. L'évacuation de l'aimant a été contrôlée chez tous les sujets. Tous les sujets ont bien supporté l'examen. Le marqueur a pu être détecté de l'oesophage au rectum. La trajectoire ainsi constituée représente une conformation de l'anatomie digestive : une bonne superposition de celle-ci à l'anatomie est obtenue à partir des images de radiologie conventionnelle (CT-scan, lavement à la gastrografine). Les mouvements de l'aimant ont été caractérisés selon leur périodicité, leur amplitude ou leur vitesse pour chaque segment du tractus digestif. Ces informations physiologiques sont bien corrélées à celles obtenues par des méthodes établies d'étude de la motilité gastro-intestinale. Ce travail démontre la faisabilité d'un examen de la motilité gastro-intestinal chez l'Homme par la méthode de Magnet Tracking. La technique fournit les données anatomiques et permet d'analyser en temps réel la dynamique des mouvements du tube digestif. Cette méthode peu invasive ouvre d'intéressantes perspectives pour l'étude de motilité dans des conditions physiologiques et pathologiques. Des expériences visant à valider cette approche en tant que méthode clinique sont en voie de réalisation dans plusieurs centres en Suisse et à l'étranger. SUMMARY Methodological improvements realised over the last decades have permitted a better understanding of gastrointestinal motility. Nevertheless, a method allowing a continuous following of lumina' contents is still lacking. In order to study the human digestive tract motility, a new minimally invasive technique was developed at the Department of Physiology in collaboration with Swiss Federal Institute of Technology. The method is based on the detection of magnetic field generated by swallowed ferromagnetic materials. The aim of our work was to demonstrate the feasibility of this new approach to study the human gastrointestinal motility. The magnet used was a cylinder (ø6x7mm, 0.2 cm3) coated with silicon. The magnet tracking system consisted of a 4x4 matrix of sensors based on the Hall effect Signals from the sensors were digitised and sent to a laptop computer for processing and storage. Specific software was conceived to analyse in real time the progression of the magnet through the gastrointestinal tube. Ten young and healthy volunteers were enrolled in the study. After a fasting period of 12 hours, they swallowed the magnet. The pill was then tracked for two consecutive days for 34 hours on average. Each subject was studied once except one who was studied seven times. Every subject laid on his back for the entire experiment but could interrupt it at anytime. Evacuation of the magnet was controlled in all subjects. The examination was well tolerated. The pill could be followed from the esophagus to the rectum. The trajectory of the magnet represented a "mould" of the anatomy of the digestive tube: a good superimposition with radiological anatomy (gastrografin contrast and CT) was obtained. Movements of the magnet were characterized by periodicity, velocity, and amplitude of displacements for every segment of the digestive tract. The physiological information corresponded well to data from current methods of studying gastrointestinal motility. This work demonstrates the feasibility of the new approach in studies of human gastrointestinal motility. The technique allows to correlate in real time the dynamics of digestive movements with the anatomical data. This minimally invasive method is ready for studies of human gastrointestinal motility under physiological as well as pathological conditions. Studies aiming at validation of this new approach as a clinically relevant tool are being realised in several centres in Switzerland and abroad. Abstract: A new minimally invasive technique allowing for anatomical mapping and motility studies along the entire human digestive system is presented. The technique is based on continuous tracking of a small magnet progressing through the digestive tract. The coordinates of the magnet are calculated from signals recorded by 16 magnetic field sensors located over the abdomen. The magnet position, orientation and trajectory are displayed in real time. Ten young healthy volunteers were followed during 34 h. The technique was well tolerated and no complication was encountered, The information obtained was 3-D con-figuration of the digestive tract and dynamics of the magnet displacement (velocity, transit time, length estimation, rhythms). In the same individual, repea-ted examination gave very reproducible results. The anatomical and physiological information obtained corresponded well to data from current methods and imaging. This simple, minimally invasive technique permits examination of the entire digestive tract and is suitable for both research and clinical studies. In combination with other methods, it may represent a useful tool for studies of Cl motility with respect to normal and pathological conditions.

Real-Time implementation of a blind authentication method using self-synchronous speech watermarking

A blind speech watermarking scheme that meets hard real-time deadlines is presented and implemented. In addition, one of the key issues in these block-oriented watermarking techniques is to preserve the synchronization. Namely, to recover the exact position of each block in the mark extract process. In fact, the presented scheme can be split up into two distinguished parts, the synchronization and the information mark methods. The former is embedded into the time domain and it is fast enough to be run meeting real-time requirements. The latter contains the authentication information and it is embedded into the wavelet domain. The synchronization and information mark techniques are both tunable in order to allow a con gurable method. Thus, capacity, transparency and robustness can be con gured depending on the needs. It makes the scheme useful for professional applications, such telephony authentication or even sending information throw radio applications.

Low intensity vs. self-guided internet-delivered psychotherapy for major depression: a multicenter, controlled, randomized study.

BACKGROUND Major depression will become the second most important cause of disability in 2020. Computerized cognitive-behaviour therapy could be an efficacious and cost-effective option for its treatment. No studies on cost-effectiveness of low intensity vs self-guided psychotherapy has been carried out. The aim of this study is to assess the efficacy of low intensity vs self-guided psychotherapy for major depression in the Spanish health system. METHODS The study is made up of 3 phases: 1.- Development of a computerized cognitive-behaviour therapy for depression tailored to Spanish health system. 2.- Multicenter controlled, randomized study: A sample (N=450 patients) with mild/moderate depression recruited in primary care. They should have internet availability at home, not receive any previous psychological treatment, and not suffer from any other severe somatic or psychological disorder. They will be allocated to one of 3 treatments: a) Low intensity Internet-delivered psychotherapy + improved treatment as usual (ITAU) by GP, b) Self-guided Internet-delivered psychotherapy + ITAU or c) ITAU. Patients will be diagnosed with MINI psychiatric interview. Main outcome variable will be Beck Depression Inventory. It will be also administered EuroQol 5D (quality of life) and Client Service Receipt Inventory (consume of health and social services). Patients will be assessed at baseline, 3 and 12 months. An intention to treat and a per protocol analysis will be performed. DISCUSSION The comparisons between low intensity and self-guided are infrequent, and also a comparative economic evaluation between them and compared with usual treatment in primary. The strength of the study is that it is a multicenter, randomized, controlled trial of low intensity and self-guided Internet-delivered psychotherapy for depression in primary care, being the treatment completely integrated in primary care setting. TRIAL REGISTRATION Clinical Trials NCT01611818.

Positional scanning-synthetic peptide library-based analysis of self- and pathogen-derived peptide cross-reactivity with tumor-reactive Melan-A-specific CTL.

Synthetic combinatorial peptide libraries in positional scanning format (PS-SCL) have recently emerged as a useful tool for the analysis of T cell recognition. This includes identification of potentially cross-reactive sequences of self or pathogen origin that could be relevant for the understanding of TCR repertoire selection and maintenance, as well as of the cross-reactive potential of Ag-specific immune responses. In this study, we have analyzed the recognition of sequences retrieved by using a biometric analysis of the data generated by screening a PS-SCL with a tumor-reactive CTL clone specific for an immunodominant peptide from the melanocyte differentiation and tumor-associated Ag Melan-A. We found that 39% of the retrieved peptides were recognized by the CTL clone used for PS-SCL screening. The proportion of peptides recognized was higher among those with both high predicted affinity for the HLA-A2 molecule and high predicted stimulatory score. Interestingly, up to 94% of the retrieved peptides were cross-recognized by other Melan-A-specific CTL. Cross-recognition was at least partially focused, as some peptides were cross-recognized by the majority of CTL. Importantly, stimulation of PBMC from melanoma patients with the most frequently recognized peptides elicited the expansion of heterogeneous CD8(+) T cell populations, one fraction of which cross-recognized Melan-A. Together, these results underline the high predictive value of PS-SCL for the identification of sequences cross-recognized by Ag-specific T cells.

Effectiveness of two interventions based on improving patient-practitioner communication on diabetes self-management in patients with low educational level: study protocol of a clustered randomized trial in primary care.

BACKGROUND In the last decades the presence of social inequalities in diabetes care has been observed in multiple countries, including Spain. These inequalities have been at least partially attributed to differences in diabetes self-management behaviours. Communication problems during medical consultations occur more frequently to patients with a lower educational level. The purpose of this cluster randomized trial is to determine whether an intervention implemented in a General Surgery, based in improving patient-provider communication, results in a better diabetes self-management in patients with lower educational level. A secondary objective is to assess whether telephone reinforcement enhances the effect of such intervention. We report the design and implementation of this on-going study. METHODS/DESIGN The study is being conducted in a General Practice located in a deprived neighbourhood of Granada, Spain. Diabetic patients 18 years old or older with a low educational level and inadequate glycaemic control (HbA1c > 7%) were recruited. General Practitioners (GPs) were randomised to three groups: intervention A, intervention B and control group. GPs allocated to intervention groups A and B received training in communication skills and are providing graphic feedback about glycosylated haemoglobin levels. Patients whose GPs were allocated to group B are additionally receiving telephone reinforcement whereas patients from the control group are receiving usual care. The described interventions are being conducted during 7 consecutive medical visits which are scheduled every three months. The main outcome measure will be HbA1c; blood pressure, lipidemia, body mass index and waist circumference will be considered as secondary outcome measures. Statistical analysis to evaluate the effectiveness of the interventions will include multilevel regression analysis with three hierarchical levels: medical visit level, patient level and GP level. DISCUSSION The results of this study will provide new knowledge about possible strategies to promote a better diabetes self-management in a particularly vulnerable group. If effective, this low cost intervention will have the potential to be easily incorporated into routine clinical practice, contributing to decrease health inequalities in diabetic patients. TRIAL REGISTRATION Clinical Trials U.S. National Institutes of Health, NCT01849731.

Quantization of energy and writhe in self-repelling knots

Probably the most natural energy functional to be considered for knotted strings is that given by electrostatic repulsion. In the absence of counter-charges, a charged, knotted string evolving along the energy gradient of electrostatic repulsion would progressively tighten its knotted domain into a point on a perfectly circular string. However, in the presence of charge screening self-repelling knotted strings can be stabilized. It is known that energy functionals in which repulsive forces between repelling charges grow inversely proportionally to the third or higher power of their relative distance stabilize self-repelling knots. Especially interesting is the case of the third power since the repulsive energy becomes scale invariant and does not change upon Mobius transformations (reflections in spheres) of knotted trajectories. We observe here that knots minimizing their repulsive Mobius energy show quantization of the energy and writhe (measure of chirality) within several tested families of knots.

Good agreements between self and clinician-collected specimens for the detection of human papillomavirus in Brazilian patients

Women infected with human papillomavirus (HPV) are at a higher risk of developing cervical lesions. In the current study, self and clinician-collected vaginal and cervical samples from women were processed to detect HPV DNA using polymerase chain reaction (PCR) with PGMY09/11 primers. HPV genotypes were determined using type-specific PCR. HPV DNA detection showed good concordance between self and clinician-collected samples (84.6%; kappa = 0.72). HPV infection was found in 30% women and genotyping was more concordant among high-risk HPV (HR-HPV) than low-risk HPV (HR-HPV). HPV16 was the most frequently detected among the HR-HPV types. LR-HPV was detected at a higher frequency in self-collected; however, HR-HPV types were more frequently identified in clinician-collected samples than in self-collected samples. HPV infections of multiple types were detected in 20.5% of clinician-collected samples and 15.5% of self-collected samples. In this study, we demonstrated that the HPV DNA detection rate in self-collected samples has good agreement with that of clinician-collected samples. Self-collected sampling, as a primary prevention strategy in countries with few resources, could be effective for identifying cases of HR-HPV, being more acceptable. The use of this method would enhance the coverage of screening programs for cervical cancer.

Trends in self-reported past alcoholic beverage consumption and ethanol intake from 1950 to 1995 observed in eight European countries participating in the European Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE To describe the trends of self-reported past consumption of alcoholic beverages and ethanol intake from 1950 to 1995 within the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN Data on consumption of beer/cider, wine and liqueur/spirits were obtained retrospectively at age 20, 30 and 40 years to calculate average consumption and ethanol intake for the time periods 1950-1975 (at age 20), 1960-1985 (at age 30) and 1970-1995 (at age 40). Regression analysis was conducted with the time period data to assess trends in past alcoholic beverage consumption and ethanol intake with time. SETTING The EPIC project. SUBJECTS In total, 392 064 EPIC participants (275 249 women and 116 815 men) from 21 study centres in eight European countries. RESULTS Generally, increases in beer/cider consumption were observed for most EPIC centres for 1950-1975, 1960-1985 and 1970-1995. Trends in wine consumption differed according to geographical location: downward trends with time were observed for men in southern European EPIC centres, upward trends for those in middle/northern European study centres. For women, similar but less pronounced trends were observed. Because wine consumption was the major contributor to ethanol intake for both men and women in most study centres, time trends for ethanol intake showed a similar geographical pattern to that of wine consumption. CONCLUSION The different trends in alcoholic beverage consumption and ethanol intake suggest that information depicting lifetime history of ethanol intake should be included in analyses of the relationship between ethanol and chronic diseases, particularly in multi-centre studies such as EPIC.

Characteristics and effectiveness of diabetes self-management educational programs targeted to racial/ethnic minority groups: a systematic review, meta-analysis and meta-regression.

BACKGROUND It is not clear to what extent educational programs aimed at promoting diabetes self-management in ethnic minority groups are effective. The aim of this work was to systematically review the effectiveness of educational programs to promote the self-management of racial/ethnic minority groups with type 2 diabetes, and to identify programs' characteristics associated with greater success. METHODS We undertook a systematic literature review. Specific searches were designed and implemented for Medline, EMBASE, CINAHL, ISI Web of Knowledge, Scirus, Current Contents and nine additional sources (from inception to October 2012). We included experimental and quasi-experimental studies assessing the impact of educational programs targeted to racial/ethnic minority groups with type 2 diabetes. We only included interventions conducted in countries members of the OECD. Two reviewers independently screened citations. Structured forms were used to extract information on intervention characteristics, effectiveness, and cost-effectiveness. When possible, we conducted random-effects meta-analyses using standardized mean differences to obtain aggregate estimates of effect size with 95% confidence intervals. Two reviewers independently extracted all the information and critically appraised the studies. RESULTS We identified thirty-seven studies reporting on thirty-nine educational programs. Most of them were conducted in the US, with African American or Latino participants. Most programs obtained some benefits over standard care in improving diabetes knowledge, self-management behaviors and clinical outcomes. A meta-analysis of 20 randomized controlled trials (3,094 patients) indicated that the programs produced a reduction in glycated hemoglobin of -0.31% (95% CI -0.48% to -0.14%). Diabetes knowledge and self-management measures were too heterogeneous to pool. Meta-regressions showed larger reduction in glycated hemoglobin in individual and face to face delivered interventions, as well as in those involving peer educators, including cognitive reframing techniques, and a lower number of teaching methods. The long-term effects remain unknown and cost-effectiveness was rarely estimated. CONCLUSIONS Diabetes self-management educational programs targeted to racial/ethnic minority groups can produce a positive effect on diabetes knowledge and on self-management behavior, ultimately improving glycemic control. Future programs should take into account the key characteristics identified in this review.