Clustering the Brain With "CluB": A New Toolbox for Quantitative Meta-Analysis of Neuroimaging Data.

In this paper we describe and validate a new coordinate-based method for meta-analysis of neuroimaging data based on an optimized hierarchical clustering algorithm: CluB (Clustering the Brain). The CluB toolbox permits both to extract a set of spatially coherent clusters of activations from a database of stereotactic coordinates, and to explore each single cluster of activation for its composition according to the cognitive dimensions of interest. This last step, called "cluster composition analysis," permits to explore neurocognitive effects by adopting a factorial-design logic and by testing the working hypotheses using either asymptotic tests, or exact tests either in a classic inference, or in a Bayesian-like context. To perform our validation study, we selected the fMRI data from 24 normal controls involved in a reading task. We run a standard random-effects second level group analysis to obtain a "Gold Standard" of reference. In a second step, the subject-specific reading effects (i.e., the linear t-contrast "reading > baseline") were extracted to obtain a coordinates-based database that was used to run a meta-analysis using both CluB and the popular Activation Likelihood Estimation method implemented in the software GingerALE. The results of the two meta-analyses were compared against the "Gold Standard" to compute performance measures, i.e., sensitivity, specificity, and accuracy. The GingerALE method obtained a high level of accuracy (0.967) associated with a high sensitivity (0.728) and specificity (0.971). The CluB method obtained a similar level of accuracy (0.956) and specificity (0.969), notwithstanding a lower level of sensitivity (0.14) due to the lack of prior Gaussian transformation of the data. Finally, the two methods obtained a good-level of concordance (AC1 = 0.93). These results suggested that methods based on hierarchical clustering (and post-hoc statistics) and methods requiring prior Gaussian transformation of the data can be used as complementary tools, with the GingerALE method being optimal for neurofunctional mapping of pooled data according to simpler designs, and the CluB method being preferable to test more specific, and localized, neurocognitive hypotheses according to factorial designs.

Modelling the distribution of health-related quality of life of advanced melanoma patients in a longitudinal multi-centre clinical trial using M-quantile random effects regression.

Health-related quality of life assessment is important in the clinical evaluation of patients with metastatic disease that may offer useful information in understanding the clinical effectiveness of a treatment. To assess if a set of explicative variables impacts on the health-related quality of life, regression models are routinely adopted. However, the interest of researchers may be focussed on modelling other parts (e.g. quantiles) of this conditional distribution. In this paper, we present an approach based on quantile and M-quantile regression to achieve this goal. We applied the methodologies to a prospective, randomized, multi-centre clinical trial. In order to take into account the hierarchical nature of the data we extended the M-quantile regression model to a three-level random effects specification and estimated it by maximum likelihood.

Hierarchical modeling of indoor radon concentration: how much do geology and building factors matter?

Radon is a natural gas known to be the main contributor to natural background radiation exposure and only second to smoking as major leading cause of lung cancer. The main concern is in indoor environments where the gas tends to accumulate and can reach high concentrations. The primary contributor of this gas into the building is from the soil although architectonic characteristics, such as building materials, can largely affect concentration values. Understanding the factors affecting the concentration in dwellings and workplaces is important both in prevention, when the construction of a new building is being planned, and in mitigation when the amount of Radon detected inside a building is too high. In this paper we investigate how several factors, such as geologic typologies of the soil and a range of building characteristics, impact on indoor concentration focusing, in particular, on how concentration changes as a function of the floor level. Adopting a mixed effects model to account for the hierarchical nature of the data, we also quantify the extent to which such measurable factors manage to explain the variability of indoor radon concentration.

Modelling the progression of bird migration with conditional autoregressive models applied to ringing data.

Migration is a fundamental stage in the life history of several taxa, including birds, and is under strong selective pressure. At present, the only data that may allow for both an assessment of patterns of bird migration and for retrospective analyses of changes in migration timing are the databases of ring recoveries. We used ring recoveries of the Barn Swallow Hirundo rustica collected from 1908-2008 in Europe to model the calendar date at which a given proportion of birds is expected to have reached a given geographical area ('progression of migration') and to investigate the change in timing of migration over the same areas between three time periods (1908-1969, 1970-1990, 1991-2008). The analyses were conducted using binomial conditional autoregressive (CAR) mixed models. We first concentrated on data from the British Isles and then expanded the models to western Europe and north Africa. We produced maps of the progression of migration that disclosed local patterns of migration consistent with those obtained from the analyses of the movements of ringed individuals. Timing of migration estimated from our model is consistent with data on migration phenology of the Barn Swallow available in the literature, but in some cases it is later than that estimated by data collected at ringing stations, which, however, may not be representative of migration phenology over large geographical areas. The comparison of median migration date estimated over the same geographical area among time periods showed no significant advancement of spring migration over the whole of Europe, but a significant advancement of autumn migration in southern Europe. Our modelling approach can be generalized to any records of ringing date and locality of individuals including those which have not been recovered subsequently, as well as to geo-referenced databases of sightings of migratory individuals.

Endovenous laser ablation of great and small saphenous vein incompetence with a 1470-nm laser and radial fiber.

OBJECTIVE: Endovenous laser ablation (EVLA) of great (GSV) and small saphenous vein (SSV) chronic insufficiency with 1470-nm diode laser and radial fiber yields good short-term results. The aim of this study was to assess its efficacy after at least 12 months of follow-up. METHODS: We performed a prospective interventional cohort study in an ambulatory care/day surgery setting. Consecutive patients with chronic, symptomatic GSV or SSV insufficiency were treated by EVLA with a 1470-nm diode laser and a radial fiberoptic. Patients were recruited between 2008 and 2011, and the follow-up was completed in 2012. All patients underwent clinical and echo color Doppler evaluations during follow-up. The primary outcome was the incidence of echo color Doppler-confirmed failures during follow-up. We also investigated potential associations between failures and patients' characteristics, echo color Doppler findings, or surgical features. The secondary outcome was the postoperative pain course. RESULTS: The planned 12-month follow-up was completed in 372 patients. Echo color Doppler-confirmed failures occurred in 37 (12%) of 310 patients with GSV insufficiency, whereas none of 62 patients with SSV insufficiency experienced a failure. Multiple Cox proportional hazards regression analysis showed a significant association of failures with a Clinical, Etiologic, Anatomic, and Pathologic class C ≥4 and a mean confluence of the superficial inguinal veins diameter ≥9 mm in patients with GSV insufficiency. Postoperative pain course was favorable. More than two thirds of the patients were asymptomatic at 7 days. CONCLUSIONS: EVLA with 1470-nm diode laser and radial fiberoptic is effective for treatment of GSV and especially SSV insufficiency and is well tolerated by the patients.

Six-year follow-up of endovenous laser ablation for great saphenous vein incompetence.

OBJECTIVE: Treatment of chronic venous insufficiency of the great saphenous veins by endovenous laser ablation yields good short- and medium-term results, as assessed clinically and technically by echo-color-Doppler. At present, scarce data are available on the long-term results of endovenous laser ablation. We wanted to assess the long-term efficacy of endovenous laser ablation. METHODS: We performed a prospective 6-year follow-up cohort study, with recruitment between 2003 and 2004, and the follow-up completed in 2010. The setting was an ambulatory care/day surgery. Of 209 consecutive patients who underwent endovenous laser ablation at our institution during the recruitment period, five (2.4%) did not complete the procedure due to technical reasons. Of 204 patients who successfully completed the intervention, 14 (6.8%) were lost for follow-up, and 190 completed the planned 6-year follow-up. The intervention was an endovenous laser ablation using a 980-nm laser diode. Clinical and echo-color-Doppler evaluations were regularly scheduled for all patients during the planned follow-up period. The incidence of clinical and echo-color-Doppler confirmed endovenous laser ablation failures over a 6-year follow-up period. Potential associations between failures and patients' characteristics, echo-color-Doppler findings, or surgical features were also investigated. RESULTS: Symptomatic clinical endovenous laser ablation failures occurred in 22 (11.6%; 95% confidence interval [CI], 7.4-17.0%) patients; while 57 (30.0%; 95% CI, 23.6-37.1%) had echo-color-Doppler-confirmed failures. Only two patients (1.1%; 95% CI, 0.1%-3.8%) had both symptomatic clinical and echo-color-Doppler-confirmed failures. Three features of the great saphenous vein: an "atypical" junction, a junction diameter ≥8 mm, and a mean trunk diameter ≥8 mm, were independently associated with echo-color-Doppler-confirmed failures on multivariate logistic regression analysis. CONCLUSIONS: Six years after endovenous laser ablation, most patients were improved on clinical grounds, and more than two-thirds had no saphenous insufficiency at echo-color-Doppler. Only a minority had both clinical and echo-color-Doppler-confirmed failures. Anatomical features of the junction and the saphenous diameter both at the junction and at the trunk independently predicted echo-color-Doppler-confirmed failures.

A geostatistical approach to assess the spatial association between indoor radon concentration, geological features and building characteristics: the case of Lombardy, Northern Italy.

Radon is a natural gas known to be the main contributor to natural background radiation exposure and second to smoking, a major leading cause of lung cancer. The main source of radon is the soil, but the gas can enter buildings in many different ways and reach high indoor concentrations. Monitoring surveys have been promoted in many countries in order to assess the exposure of people to radon. In this paper, two complementary aspects are investigated. Firstly, we mapped indoor radon concentration in a large and inhomogeneous region using a geostatistical approach which borrows strength from the geologic nature of the soil. Secondly, knowing that geologic and anthropogenic factors, such as building characteristics, can foster the gas to flow into a building or protect against this, we evaluated these effects through a multiple regression model which takes into account the spatial correlation of the data. This allows us to rank different building typologies, identified by architectonic and geological characteristics, according to their proneness to radon. Our results suggest the opportunity to differentiate construction requirements in a large and inhomogeneous area, as the one considered in this paper, according to different places and provide a method to identify those dwellings which should be monitored more carefully.