Decreasing Proportion of Recent Infections among Newly Diagnosed HIV-1 Cases in Switzerland, 2008 to 2013 Based on Line-Immunoassay-Based Algorithms.

BACKGROUND: HIV surveillance requires monitoring of new HIV diagnoses and differentiation of incident and older infections. In 2008, Switzerland implemented a system for monitoring incident HIV infections based on the results of a line immunoassay (Inno-Lia) mandatorily conducted for HIV confirmation and type differentiation (HIV-1, HIV-2) of all newly diagnosed patients. Based on this system, we assessed the proportion of incident HIV infection among newly diagnosed cases in Switzerland during 2008-2013. METHODS AND RESULTS: Inno-Lia antibody reaction patterns recorded in anonymous HIV notifications to the federal health authority were classified by 10 published algorithms into incident (up to 12 months) or older infections. Utilizing these data, annual incident infection estimates were obtained in two ways, (i) based on the diagnostic performance of the algorithms and utilizing the relationship 'incident = true incident + false incident', (ii) based on the window-periods of the algorithms and utilizing the relationship 'Prevalence = Incidence x Duration'. From 2008-2013, 3'851 HIV notifications were received. Adult HIV-1 infections amounted to 3'809 cases, and 3'636 of them (95.5%) contained Inno-Lia data. Incident infection totals calculated were similar for the performance- and window-based methods, amounting on average to 1'755 (95% confidence interval, 1588-1923) and 1'790 cases (95% CI, 1679-1900), respectively. More than half of these were among men who had sex with men. Both methods showed a continuous decline of annual incident infections 2008-2013, totaling -59.5% and -50.2%, respectively. The decline of incident infections continued even in 2012, when a 15% increase in HIV notifications had been observed. This increase was entirely due to older infections. Overall declines 2008-2013 were of similar extent among the major transmission groups. CONCLUSIONS: Inno-Lia based incident HIV-1 infection surveillance proved useful and reliable. It represents a free, additional public health benefit of the use of this relatively costly test for HIV confirmation and type differentiation.

On-line life history calendar and sensitive topics : A pilot study

The use of the life history calendar (LHC) or the event history calendar as tools for collecting retrospective data has received increasing attention in many fields of social science and medicine. However, little research has examined the use of this method with web-based surveys. In this study, we adapted this method to an on-line setting to collect information about young adults' life histories, sexual behaviors, and substance use. We hypothesized that the LHC method would help respondents to date sensitive and non-sensitive events more precisely than when using a conventional questionnaire. We conducted an experimental design study comparing university students' responses to an on-line LHC and a conventional on-line question list. A test-retest design in which the respondents completed the survey again two weeks later was also applied to test the precision and reliability of the participants' dating of events. The results showed that whereas the numbers of sensitive and non-sensitive events were generally similar for the two on-line questionnaires, the responses obtained with the LHC were more consistent across the two administrations. Analyses of the respondents' on-line behavior while completing the LHC confirmed that respondents used the LHC's graphic interface to correct and reedit previous answers, thus decreasing data errors. (C) 2015 Elsevier Ltd. All rights reserved.

Change points detection in crime-related time series: an on-line fuzzy approach based on a shape space representation

The extension of traditional data mining methods to time series has been effectively applied to a wide range of domains such as finance, econometrics, biology, security, and medicine. Many existing mining methods deal with the task of change points detection, but very few provide a flexible approach. Querying specific change points with linguistic variables is particularly useful in crime analysis, where intuitive, understandable, and appropriate detection of changes can significantly improve the allocation of resources for timely and concise operations. In this paper, we propose an on-line method for detecting and querying change points in crime-related time series with the use of a meaningful representation and a fuzzy inference system. Change points detection is based on a shape space representation, and linguistic terms describing geometric properties of the change points are used to express queries, offering the advantage of intuitiveness and flexibility. An empirical evaluation is first conducted on a crime data set to confirm the validity of the proposed method and then on a financial data set to test its general applicability. A comparison to a similar change-point detection algorithm and a sensitivity analysis are also conducted. Results show that the method is able to accurately detect change points at very low computational costs. More broadly, the detection of specific change points within time series of virtually any domain is made more intuitive and more understandable, even for experts not related to data mining.

Validation and long-term evaluation of a modified on-line chiral analytical method for therapeutic drug monitoring of (R,S)-methadone in clinical samples.

Matrix effects, which represent an important issue in liquid chromatography coupled to mass spectrometry or tandem mass spectrometry detection, should be closely assessed during method development. In the case of quantitative analysis, the use of stable isotope-labelled internal standard with physico-chemical properties and ionization behaviour similar to the analyte is recommended. In this paper, an example of the choice of a co-eluting deuterated internal standard to compensate for short-term and long-term matrix effect in the case of chiral (R,S)-methadone plasma quantification is reported. The method was fully validated over a concentration range of 5-800 ng/mL for each methadone enantiomer with satisfactory relative bias (-1.0 to 1.0%), repeatability (0.9-4.9%) and intermediate precision (1.4-12.0%). From the results obtained during validation, a control chart process during 52 series of routine analysis was established using both intermediate precision standard deviation and FDA acceptance criteria. The results of routine quality control samples were generally included in the +/-15% variability around the target value and mainly in the two standard deviation interval illustrating the long-term stability of the method. The intermediate precision variability estimated in method validation was found to be coherent with the routine use of the method. During this period, 257 trough concentration and 54 peak concentration plasma samples of patients undergoing (R,S)-methadone treatment were successfully analysed for routine therapeutic drug monitoring.

Producing on-line ultrapure dialysis fluid.

The process of on-line generation of ultrapure dialysis fluid is a core prerequisite for the safe execution of modern renal replacement therapies such as on-line hemodiafiltration and high-flux hemodialysis. In these extracorporeal treatments with variable degrees of convection, significant volumes of plasma water are removed and replaced with dialysis fluid, which must occur without causing harm to the patient. Historically, on-line generation of sterile and pyrogen-free physiological substitution fluid by the process of membrane ultrafiltration of fresh dialysis fluid has its origin in hemofiltration, a purely convective therapy. Development of this and later therapies is described in the historical context of a successful effort over decades to overcome the above formidable challenge, which was provided jointly by pioneering clinical investigators and a resourceful dialysis industry.

Statistical evaluation of the influence of writing postures on on-line signatures. Study of the impact of time.

The aim of this study is to investigate the influence of unusual writing positions on a person's signature, in comparison to a standard writing position. Ten writers were asked to sign their signature six times, in each of four different writing positions, including the standard one. In order to take into consideration the effect of the day-to-day variation, this same process was repeated over 12 sessions, giving a total of 288 signatures per subject. The signatures were collected simultaneously in an off-line and on-line acquisition mode, using an interactive tablet and a ballpoint pen. Unidimensional variables (height to width ratio; time with or without in air displacement) and time-dependent variables (pressure; X and Y coordinates; altitude and azimuth angles) were extracted from each signature. For the unidimensional variables, the position effect was assessed through ANOVA and Dunnett contrast tests. Concerning the time-dependent variables, the signatures were compared by using dynamic time warping, and the position effect was evaluated through classification by linear discriminant analysis. Both of these variables provided similar results: no general tendency regarding the position factor could be highlighted. The influence of the position factor varies according to the subject as well as the variable studied. The impact of the session factor was shown to cover the impact that could be ascribed to the writing position factor. Indeed, the day-to-day variation has a greater effect than the position factor on the studied signature variables. The results of this study suggest guidelines for best practice in the area of signature comparisons and demonstrate the importance of a signature collection procedure covering an adequate number of sampling sessions, with a sufficient number of samples per session.

Do pseudo-absence selection strategies influence species distribution models and their predictions? An information-theoretic approach based on simulated data

Background Multiple logistic regression is precluded from many practical applications in ecology that aim to predict the geographic distributions of species because it requires absence data, which are rarely available or are unreliable. In order to use multiple logistic regression, many studies have simulated "pseudo-absences" through a number of strategies, but it is unknown how the choice of strategy influences models and their geographic predictions of species. In this paper we evaluate the effect of several prevailing pseudo-absence strategies on the predictions of the geographic distribution of a virtual species whose "true" distribution and relationship to three environmental predictors was predefined. We evaluated the effect of using a) real absences b) pseudo-absences selected randomly from the background and c) two-step approaches: pseudo-absences selected from low suitability areas predicted by either Ecological Niche Factor Analysis: (ENFA) or BIOCLIM. We compared how the choice of pseudo-absence strategy affected model fit, predictive power, and information-theoretic model selection results. Results Models built with true absences had the best predictive power, best discriminatory power, and the "true" model (the one that contained the correct predictors) was supported by the data according to AIC, as expected. Models based on random pseudo-absences had among the lowest fit, but yielded the second highest AUC value (0.97), and the "true" model was also supported by the data. Models based on two-step approaches had intermediate fit, the lowest predictive power, and the "true" model was not supported by the data. Conclusion If ecologists wish to build parsimonious GLM models that will allow them to make robust predictions, a reasonable approach is to use a large number of randomly selected pseudo-absences, and perform model selection based on an information theoretic approach. However, the resulting models can be expected to have limited fit.

Numerical analysis of wave-induced fluid flow effects on seismic data: Application to monitoring of CO2 storage at the Sleipner Field

In this work we analyze how patchy distributions of CO2 and brine within sand reservoirs may lead to significant attenuation and velocity dispersion effects, which in turn may have a profound impact on surface seismic data. The ultimate goal of this paper is to contribute to the understanding of these processes within the framework of the seismic monitoring of CO2 sequestration, a key strategy to mitigate global warming. We first carry out a Monte Carlo analysis to study the statistical behavior of attenuation and velocity dispersion of compressional waves traveling through rocks with properties similar to those at the Utsira Sand, Sleipner field, containing quasi-fractal patchy distributions of CO2 and brine. These results show that the mean patch size and CO2 saturation play key roles in the observed wave-induced fluid flow effects. The latter can be remarkably important when CO2 concentrations are low and mean patch sizes are relatively large. To analyze these effects on the corresponding surface seismic data, we perform numerical simulations of wave propagation considering reservoir models and CO2 accumulation patterns similar to the CO2 injection site in the Sleipner field. These numerical experiments suggest that wave-induced fluid flow effects may produce changes in the reservoir's seismic response, modifying significantly the main seismic attributes usually employed in the characterization of these environments. Consequently, the determination of the nature of the fluid distributions as well as the proper modeling of the seismic data constitute important aspects that should not be ignored in the seismic monitoring of CO2 sequestration problems.

Pseudoxanthoma elasticum : evaluation of diagnostic criteria based on molecular data

RÉSUMÉ EN FRANCAIS : Introduction: Le pseudoxanthome élastique (PXE) est une maladie génétique. Les mutations responsables ont été localisées au niveau du gène codant le transporteur transmembranaire ABC-C6. Des calcifications pathologiques des fibres élastiques de la peau, des yeux et du système cardiovasculaire en sont la conséquence. Buts: Evaluer les critères diagnostiques actuels du PXE en se basant sur les données moléculaires. Méthodes: 142 sujets provenant de 10 familles avec une anamnèse familiale positive pour le PXE ont été investiguées sur le plan clinique, histopathologique et génétique. Résultats: 25 sujets se sont avérés être homozygotes pour le gène PXE muté. 23 d'entre eux ont présenté les manifestations cliniques et histopathologique typiques. Les deux autres souffraient d'une élastose et d'une dégénérescence maculaire si importante qu'un diagnostic de PXE ne pouvait pas être confirmé cliniquement. 67 sujets se sont révélés être des porteurs hétérozygotes et 50 ne présentaient pas de mutation. De ces 117 sujets, 116 n'ont montré aucune lésion cutanée ou ophtalmique pouvant correspondre au PXE. Un seul des sujets sans mutation a présenté une importante élastose solaire ainsi qu'une cicatrisation de la rétine, imitant les lésions typiques du PXE. Quatre des 67 sujets hétérozygotes ont eu une biopsie de peau, dont les analyses histopathologique se sont avérées normales. Conclusion: Dans notre cohorte de patients, le PXE était transmis exclusivement de façoh autosomique récessive. La corrélation retrouvée entre le génotype et le phénotype a permis de confirmer les critères diagnostiques majeurs actuels. Le diagnostic clinique peut être difficile, voir impossible, chez des patients atteints d'une élastose solaire importante et/ou d'une dégénérescence maculaire étendue. Dans ces cas, un test moléculaire est nécessaire afin de confirmer le diagnostic de PXE. A notre connaissance, notre étude présentée ici est le premier travail comparant des données cliniques à des données moléculaires dans le domaine du PXE. ABSTRACT : Background: Pseudoxanthoma elasticum (PXE) is a genetic disorder due to mutations in the gene encoding the transmembrane transporter protein adenosine triphosphate binding cassette (ABC)-C6, resulting in calcifications of elastic fibers in the skin, eyes and cardiovascular system. Objectives: To evaluate the diagnostic criteria for PXE based on molecular data. Methods: Of 10 families with a positive history of PXE 142 subjects were investigated for clinical symptoms, histological findings and genetic haplotype analysis. Results: Of these, 25 subjects were haplotypic homozygous for PXE and 23 had typical clinical and histopathological manifestations. Two of the 25 patients showed such marked solar elastosis and macular degeneration that PXE could not be confirmed clinically. Sixty-seven subject were haplotypic heterozygous carriers and 50 haplotypic homozygous unaffected. Of these 117 subjects, 116 showed no cutaneous or ophthalmologic signs of PXE. In one of the 50 haplotypic homozygous unaffected patients important solar elastosis and scaring of the retina mimicked PXE lesions. Only four of the 67 haplotypic heterozygous carriers had biopsies of nonlesional skin; all were histopathologically normal. Conclusions: In our patients, PXE presents as an autosomal recessive genodermatosis. Correlation of haplotype and phenotype confirmed actual major diagnostic criteria. In patients with marked solar elastosis and/ or severe macular degeneration clinical diagnosis can be impossible and molecular testing is needed to confirm the presence of PXE. To the best of our knowledge our large study compares for the first time clinical findings with molecular data.

DEA does not like positive discrimination : a comparison of alternative models based on empirical data

Due to the existence of free software and pedagogical guides, the use of data envelopment analysis (DEA) has been further democratized in recent years. Nowadays, it is quite usual for practitioners and decision makers with no or little knowledge in operational research to run themselves their own efficiency analysis. Within DEA, several alternative models allow for an environment adjustment. Five alternative models, each of them easily accessible to and achievable by practitioners and decision makers, are performed using the empirical case of the 90 primary schools of the State of Geneva, Switzerland. As the State of Geneva practices an upstream positive discrimination policy towards schools, this empirical case is particularly appropriate for an environment adjustment. The alternative of the majority of DEA models deliver divergent results. It is a matter of concern for applied researchers and a matter of confusion for practitioners and decision makers. From a political standpoint, these diverging results could lead to potentially opposite decisions. Grâce à l'existence de logiciels en libre accès et de guides pédagogiques, la méthode data envelopment analysis (DEA) s'est démocratisée ces dernières années. Aujourd'hui, il n'est pas rare que les décideurs avec peu ou pas de connaissances en recherche opérationnelle réalisent eux-mêmes leur propre analyse d'efficience. A l'intérieur de la méthode DEA, plusieurs modèles permettent de tenir compte des conditions plus ou moins favorables de l'environnement. Cinq de ces modèles, facilement accessibles et applicables par les décideurs, sont utilisés pour mesurer l'efficience des 90 écoles primaires du canton de Genève, Suisse. Le canton de Genève pratiquant une politique de discrimination positive envers les écoles défavorisées, ce cas pratique est particulièrement adapté pour un ajustement à l'environnement. La majorité des modèles DEA génèrent des résultats divergents. Ce constat est préoccupant pour les chercheurs appliqués et perturbant pour les décideurs. D'un point de vue politique, ces résultats divergents conduisent à des prises de décision différentes selon le modèle sur lequel elles sont fondées.

Microfabricated dual sprayer for on-line mass tagging of phosphopeptides.

Phosphopeptides tagging reactions by dinuclear zinc(II) complexes (1,3-bis[bis(2-pyridylmethyl)amino]-propan-2-olato dizinc(II)3+, called tag) were performed with a dual-channel microsprayer in electrospray ionization mass spectrometry. The reaction is first studied ex situ and analyzed with a commercial electrospray source. In situ reactions (i.e., inside the Taylor cone) were achieved with a dual-channel microsprayer both with the tag synthesized chemically before the experiments and with the tag electrogenerated by in situ oxidation of a zinc electrode, also used to apply the electrospray current. The device consists of a polyimide microchip with two microchannels (20 microm x 50 microm x 1 cm) etched on each side of the structure and connecting only at the tip of the microchip. We demonstrate here that mixing two solutions with different physicochemical properties inside the Taylor cone can be used to selectively tag target molecules.

Photodynamic Diagnosis of Non-muscle-invasive Bladder Cancer with Hexaminolevulinate Cystoscopy: A Meta-analysis of Detection and Recurrence Based on Raw Data.

BACKGROUND: Studies on hexaminolevulinate (HAL) cystoscopy report improved detection of bladder tumours. However, recent meta-analyses report conflicting effects on recurrence. OBJECTIVE: To assess available clinical data for blue light (BL) HAL cystoscopy on the detection of Ta/T1 and carcinoma in situ (CIS) tumours, and on tumour recurrence. DESIGN, SETTING, AND PARTICIPANTS: This meta-analysis reviewed raw data from prospective studies on 1345 patients with known or suspected non-muscle-invasive bladder cancer (NMIBC). INTERVENTION: A single application of HAL cystoscopy was used as an adjunct to white light (WL) cystoscopy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We studied the detection of NMIBC (intention to treat [ITT]: n=831; six studies) and recurrence (per protocol: n=634; three studies) up to 1 yr. DerSimonian and Laird's random-effects model was used to obtain pooled relative risks (RRs) and associated 95% confidence intervals (CIs) for outcomes for detection. RESULTS AND LIMITATIONS: BL cystoscopy detected significantly more Ta tumours (14.7%; p<0.001; odds ratio [OR]: 4.898; 95% CI, 1.937-12.390) and CIS lesions (40.8%; p<0.001; OR: 12.372; 95% CI, 6.343-24.133) than WL. There were 24.9% patients with at least one additional Ta/T1 tumour seen with BL (p<0.001), significant also in patients with primary (20.7%; p<0.001) and recurrent cancer (27.7%; p<0.001), and in patients at high risk (27.0%; p<0.001) and intermediate risk (35.7%; p=0.004). In 26.7% of patients, CIS was detected only by BL (p<0.001) and was also significant in patients with primary (28.0%; p<0.001) and recurrent cancer (25.0%; p<0.001). Recurrence rates up to 12 mo were significantly lower overall with BL, 34.5% versus 45.4% (p=0.006; RR: 0.761 [0.627-0.924]), and lower in patients with T1 or CIS (p=0.052; RR: 0.696 [0.482-1.003]), Ta (p=0.040; RR: 0.804 [0.653-0.991]), and in high-risk (p=0.050) and low-risk (p=0.029) subgroups. Some subgroups had too few patients to allow statistically meaningful analysis. Heterogeneity was minimised by the statistical analysis method used. CONCLUSIONS: This meta-analysis confirms that HAL BL cystoscopy significantly improves the detection of bladder tumours leading to a reduction of recurrence at 9-12 mo. The benefit is independent of the level of risk and is evident in patients with Ta, T1, CIS, primary, and recurrent cancer.

On-line desorption of dried blood spot: A novel approach for the direct LC/MS analysis of micro-whole blood samples.

The aim of this work is to present a new concept, called on-line desorption of dried blood spots (on-line DBS), allowing the direct analysis of a dried blood spot coupled to liquid chromatography mass spectrometry device (LC/MS). The system is based on an inox cell which can receive a blood sample (10 microL) previously spotted on a filter paper. The cell is then integrated into LC/MS system where the analytes are desorbed out of the paper towards a column switching system ensuring the purification and separation of the compounds before their detection on a single quadrupole MS coupled to atmospheric pressure chemical ionisation (APCI) source. The described procedure implies that no pretreatment is necessary in spite the analysis is based on whole blood sample. To ensure the applicability of the concept, saquinavir, imipramine, and verapamil were chosen. Despite the use of a small sampling volume and a single quadrupole detector, on-line DBS allowed the analyses of these three compounds over their therapeutic concentrations from 50 to 500 ng/mL for imipramine and verapamil and from 100 to 1000 ng/mL for saquinavir. Moreover, the method showed good repeatability with relative standard deviation (RSD) lower than 15% based on two levels of concentration (low and high). Function responses were found to be linear over the therapeutic concentration for each compound and were used to determine the concentrations of real patient samples for saquinavir. Comparison of the founded values with those of a validated method used routinely in a reference laboratory showed a good correlation between the two methods. Moreover, good selectivity was observed ensuring that no endogenous or chemical components interfered with the quantitation of the analytes. This work demonstrates the feasibility and applicability of the on-line DBS procedure for bioanalysis.