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Generalized additive models provide a flexible and easily-interpretable method for uncovering a nonlinear relationship between response and covariates. In many situations, the effect of a continuous covariate on the response varies across groups defined by the levels of a categorical variable. When confronted with a considerable number of groups defined by the levels of the categorical variable and a factor‐by‐curve interaction is detected in the model, it then becomes important to compare these regression curves. When the null hypothesis of equality of curves is rejected, leading to the clear conclusion that at least one curve is different, we may assume that individuals can be grouped into a number of classes whose members all share the same regression function. We propose a method that allows determining such groups with an automatic selection of their number by means of bootstrapping. The validity and behavior of the proposed method were evaluated through simulation studies. The applicability of the proposed method is illustrated using real data from an experimental study in neurology., This work was partially supported by project 2017/00001/006/001/097: Ayudas para el man tenimiento de actividades de investigaci ´on de institutos universitarios de investigaci ´on y grupos de investigaci´on de la Universidad de Oviedo para el ejercicio 2021. Luís Meira-Machado acknowledges financial support from Portuguese Funds through FCT - ”Fundação para a Ciência e a Tecnologia”, within the projects UIDB ˆ /00013/2020, UIDP/00013/2020. Javier Roca-Pardinas acknowledges financial support from Grant PID2020-118101GB-I00, Ministerio de Ciencia e Innovacion (MCIN/AEI /10.13039/501100011033).

The high impact of the lymph node ratio as a prognostic factor is widely established in colorectal cancer, and is being used as a categorized predictor variable in several studies. However, the cut-off points as well as the number of categories considered differ considerably in the literature. Motivated by the need to obtain the best categorization of the lymph node ratio as a predictor of mortality in colorectal cancer patients, we propose a method to select the best number of categories for a continuous variable in a logistic regression framework. Thus, to this end, we propose a bootstrap-based hypothesis test, together with a new estimation algorithm for the optimal location of the cut-off points called BackAddFor, which is an updated version of the previously proposed AddFor algorithm. The performance of the hypothesis test was evaluated by means of a simulation study, under different scenarios, yielding type I errors close to the nominal errors and good power values whenever a meaningful difference in terms of prediction ability existed. Finally, the methodology proposed was applied to the CCR-CARESS study where the lymph node ratio was included as a predictor of five-year mortality, resulting in the selection of three categories.

Adults with dyslexia may find difficulties in reading the messages on variable message signs (VMS) while driving. These signs are an essential part of the traffic communication systems, aimed at informing road users of special circumstances, such as congestion, traffic diversion, or unexpected events. A driving simulation experiment was conducted to test if complementary audio versions of the VMS would be helpful for drivers with dyslexia. Twenty adults with dyslexia and 20 matched controls participated. They were asked to classify the messages displayed on VMS posted along a simulated route, which was completed twice: one with text VMS (visual condition), and another one with text VMS plus complementary audio messages (audio + visual condition). The results showed that in the ordinary, visual condition, the participants with dyslexia needed to be closer to the VMS than controls to correctly classify the message, but, crucially, these group differences vanished when the driver received an audio version of the message (audio + visual condition). Moreover, the availability of audio versions had positive effects for all participants, as shown by higher accuracy in the message classification task, as well as better driving performance. Therefore, technologies aimed at providing audio versions of VMS can help drivers with dyslexia. A mobile application, READit VMS, which is able to provide real-time complementary audio versions of VMS, is presented as an example.

It is widely accepted that the relationship between lightning wildfire occurrence and its influencing factors vary depending on the spatial scale of analysis, making the development of models at the regional scale advisable. In this study, we analyze the effects of different biophysical variables and lightning characteristics on lightning-caused forest wildfires in Castilla y León region (Central Spain). The presence/absence of at least one lightning-caused fire in any 4 × 4-km grid cell was used as a dependent variable and vegetation type and structure, terrain, climate, and lightning characteristics were used as possible covariates. Five prediction methods were compared: a generalized linear model (GLM), a random forest model (RFM), a generalized additive model (GAM), a GAM that includes a spatial trend function (GAMs) and a spatial autoregressive model (AUREG). A GAMs with just one covariate, apart from longitude and latitude for each observation included as a combined effect, was considered the most appropriate model in terms of both predictive ability and simplicity. According to our results, the probability of a forest being affected by a lightning-caused fire is positively and nonlinearly associated with the percentage of coniferous woodlands in the landscape, suggesting that occurrence is more closely associated with vegetation type than with topography, climate, or lightning characteristics. The selected GAMs is intended to inform the Regional Government of Castilla y León (the fire and fuel agency in the region) regarding identification of areas at greatest risk so it can design long-term forest fuel and fire management strategies.

Many clinical decisions are taken based on the results of continuous diagnostic tests. Usually, only the results of one single test is taken into consideration, the interpretation of which requires a reference range for the healthy population. However, the use of two different tests, can be necessary in the diagnosis of certain diseases. This obliges a bivariate reference region be available for their interpretation. It should also be remembered that reference regions may depend on patient variables (eg, age and sex) independent of the suspected disease. However, few proposals have been made regarding the statistical modeling of such reference regions, and those put forward have always assumed a Gaussian distribution, which can be rather restrictive. The present work describes a new statistical method that allows such reference regions to be estimated with no insistence on the results being normally distributed. The proposed method is based on a bivariate location-scale model that provides probabilistic regions covering a specific percentage of the bivariate data, dependent on certain covariates. The reference region is estimated nonparametrically and the nonlinear effects of continuous covariates via polynomial kernel smoothers in additive models. The bivariate model is estimated using a backfitting algorithm, and the optimal smoothing parameters of the kernel smoothers selected by cross-validation. The model performed satisfactorily in simulation studies under the assumption of non-Gaussian conditions. Finally, the proposed methodology was found to be useful in estimating a reference region for two continuous diagnostic tests for diabetes (fasting plasma glucose and glycated hemoglobin), taking into account the age of the patient Óscar Lado-Baleato is funded by a predoctoral grant (ED481A-2018) from the Galician Government (Plan I2C)-Xunta de Galicia. This research was also supported by grants from the Carlos III Health Institute, Spain (PI16/01404 and RD16/0017/0018), and by the project MTM2017-83513-R cofinanced by the Ministry of Economy and Competitiveness (SPAIN) and the European Regional Development Fund (FEDER). This work was also supported by grants from the Galician Government: RED INBIOEST (ED341D-R2016/032), Grupo de Referencia Competitiva (ED431C 2016-025), and Grupo de Potencial Crecimiento (IN607B 2018-1). Javier Roca-Pardiñas acknowledges financial support by the Grant MTM2017-89422-P (MINECO/AEI/FEDER, UE) SI

Background The dental treatment of individuals with intellectual disability can represent a considerable professional challenge. Objective To develop a model for predicting the behavior of patients with intellectual disability in the dental office. Methods The study group comprised 250 patients with Down syndrome (DS), autism spectrum disorder (ASD), cerebral palsy (CP), idiopathic cognitive impairment or rare disorders. We collected their demographic, medical, social and behavioral information and identified potential predictors (chi-squared test). We developed stratified models (Akaike information criterion) to anticipate the patients'behavior during intraoral examinations and to discern whether the dental treatment should be performed under general anesthesia. These models were validated in a new study group consisting of 80 patients. Goodness of fit was quantified with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curve (AUC). We developed a mathematical algorithm for executing the models and developed software for its practical implementation (PREdictors of BEhavior in Dentistry, “PREBED”). Results For patients with DS, ASD and CP, the model predicting the need for physical restraint during examination achieved a PPV of 0.90, 0.85 and 1.00, respectively, and an NPV of 0.66, 0.76 and 1.00, respectively. The model predicting the need for performing treatment under general anesthesia achieved a PPV of 0.63, 1.00 and 1.00, respectively, and an NPV of 1.00, 1.00 and 0.73, respectively. However, when validating the stratified models, the percentage of poorly classified individuals (false negatives + false positives) ranged from 24% to 46.6%. Conclusions The results of the PREBED tool open the door to establishing new models implementing other potentially predictive variables.

Purpose There was a high medical need for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) when several next-generation anti-androgens (apalutamide, enzalutamide, and darolutamide) demonstrated clinically relevant delays in metastasis onset. However, to date, few publications have assessed the pooled effect of these treatments on overall survival (OS). Materials and methods We performed a systematic review and meta-analysis of all randomized, placebo-controlled studies investigating a systemic treatment in nmCRPC. Publications were identified by searching several databases on April 7, 2021. The primary objective of this analysis was to determine the OS benefit. Secondary outcomes included the relative risk (RR) of adverse events (AEs) and grade 3/4 AEs. A sensitivity analysis with simulated data was also conducted to examine the influence of the study designs on the results. Results Three randomized controlled studies (SPARTAN, PROSPER, ARAMIS) met our inclusion criteria. Pooled meta-analyses showed a significant benefit in OS with the active agents versus placebo (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.65–0.83), as well as increased risk of any grade (RR 1.09, 95% CI 1.01–1.17) and grade 3/4 AEs (RR 1.50, 95% CI 1.23–1.83). The sensitivity analysis with SPARTAN-like simulated populations demonstrated that when using ARAMIS statistical design, OS would be statistically significant in 98.1% of the cases, at a shorter follow-up and with lower number of events. Conclusions First-line treatment of nmCRPC patients with anti-androgens increased OS with an acceptable safety profile. In light of the different study designs and follow-up, results should be interpreted separately.

Over the past few years, there has been growing interest in using online methods for collecting data from large samples. However, only a few studies have administered online behavioral tasks to assess attention outside the lab. In the present study, we assessed the classic attentional functions and two vigilance components using two versions of the Attentional Networks Test for Interactions and Vigilance–executive and arousal vigilance components (ANTI-Vea): (1) a standard version, performed under typical experimental conditions (n = 314), and (2) an online version, completed outside the lab (n = 303). Both versions were equally effective in assessing (1) the main effects and interactions of phasic alertness, orienting, and executive control, and (2) the executive (i.e., a decline in the ability to detect infrequent critical signals) and the arousal (i.e., a progressive slowness and variability in responses to stimuli from the environment) vigilance decrement across time on task. Responses were generally slower in the online than in the standard version. Importantly, the split-half reliability observed for both tasks was (1) higher for executive control (~.67) than for phasic alertness and orienting (< .40), as observed in previous versions of the task, and (2) between .71 and .99 for the executive and arousal vigilance measures. We expect the present study will be of interest to researchers aiming to assess attentional functions with a valid and reliable method that, importantly, is publicly available on an open website ( https://www.ugr.es/~neurocog/ANTI/ ) and is easy to use in applied contexts.

We examined the effects of different types of cognitive distraction coming from a hands-free phone conversation on the processing of information provided by variable message signs (VMS), on driving performance indicators, and on a physiological index of mental effort (heart rate). Participants drove a route in a driving simulator and had to respond to VMS messages under three conditions: no-distraction, visuospatial distraction (attending phone calls with questions inducing visuospatial processing), and conceptual distraction (attending phone calls with questions requiring semantic memory). Results showed more errors responding to VMS messages in the visuospatial distraction condition. In addition, both types of questions increased the intraindividual variability of response distances and the heart rate, as compared to the no-distraction condition. These results provide new evidence that talking on a hands-free phone entails costs in the processing of traffic information (in particular, text messages displayed on VMS) and it increases the driver's cognitive effort. Interestingly, the cognitive distraction had no effect on the driver's control of the vehicle speed or lateral position. Therefore, the effects of potential risk factors can critically vary among the different driving subtasks due to modulatory factors, such as the level of attentional task demands (relatively high in the processing of messages on VMS, but relatively low in controlling the speed and lateral position of the vehicle in quiet traffic conditions). In consequence, the current paper provides new evidence to discuss hands-free phone policies and highlights the importance of designing technological countermeasures to prevent drivers missing critical information displayed on VMS.

Vigilance is generally understood as the ability to detect infrequent critical events through long time periods. In tasks like the Sustained Attention to Response Task (SART), participants tend to detect fewer events across time, a phenomenon known as vigilance decrement. However, vigilance might also involve sustaining a tonic arousal level. In the Psychomotor Vigilance Test (PVT), the vigilance decrement corresponds to an increment across time in both mean and variability of reaction time. New Method: The present study aimed to develop a single task Attentional Networks Test for Interactions and Vigilance executive and arousal components (ANTI-Vea) to simultaneously assess both components of vigilance (i.e., the executive vigilance as in the SART, and the arousal vigilance as in the PVT), while measuring the classic attentional functions (phasic alertness, orienting, and executive control). Results: In Experiment #1, the executive vigilance decrement was found as an increment in response bias. In Experiment #2, this result was replicated, and the arousal vigilance decrement was simultaneously observed as an increment in reaction time. Comparison with Existing Method: The ANTI-Vea solves some issues observed in the previous ANTI-V task with the executive vigilance measure (e.g., a low hit rate and no vigilance decrement). Furthermore, the new ANTI-Vea task assesses both components of vigilance together with others typical attentional functions. Conclusions: The new attentional networks test developed here may be useful to provide a better understanding of the human attentional system. The role of sensitivity and response bias in the executive vigilance decrement are discussed. Fil: Luna, Fernando Gabriel. Universidad de Granada; España. Universidad Nacional de Córdoba. Instituto de Investigaciones Psicológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Psicológicas; Argentina Fil: Marino, Julián Carlos. Universidad Nacional de Córdoba. Facultad de Psicología. Laboratorio de Psicología Cognitiva; Argentina. Universidad Nacional de Córdoba. Instituto de Investigaciones Psicológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Psicológicas; Argentina Fil: Roca, Javier. Universidad de Valencia; España Fil: Lupiáñez, Juan. Universidad de Granada; España

Would an increase in the default interletter spacing improve the legibility of words in traffic signs? Previous evidence on traffic sign design and recent studies on the cognitive processes involved in visual word recognition have provided conflicting results. The present work examined whether an increase in the default interletter spacing would improve the search of a word in direction traffic signs. To achieve this objective, twenty-two drivers participated in a driving simulation experiment. They followed a highway route and indicated whether a target place name was present among a set of distractors shown on direction traffic signs along the route. We compared the default interletter spacing of the Spanish "CC Rige" font (which is based on the internationally-used Transport font) and a 2.5-times expanded interletter spacing. The results revealed that the drivers were able to give a correct response at a distance to the traffic sign that was on average longer in the expanded than in the default spacing condition. This advantage in the legibility distance was observed in the absence of significant differences in reading accuracy, gaze behavior, or driving performance measures. Therefore, the evidence provided supports that drivers can benefit from a slight increase in interletter spacing relative to the standard spacing. Some of the design factors influencing this effect are discussed.

A group of adult individuals with dyslexia and a matched group of normally reading individuals participated in a driving simulation experiment. Participants were asked to read the word presented on every direction traffic sign encountered along a route, as far as possible from the sign, maintaining driving performance. Word frequency and word length were manipulated as within-subject factors. We analyzed (a) reading accuracy, (b) how far the sign was when the participant started to give the response, (c) where the participant looked during the time leading up to the response, and (d) the variability of the vehicle’s speed during that time and during driving on similar segments of the route that did not present the traffic signs. Individuals with dyslexia showed lower levels of performance in the reading task, the roles of word frequency and word length were more influential for them, and there was larger variability of the vehicle’s speed during the time they were attempting to read the traffic sign, which did not occur during their driving on similar segments that did not present the targeted traffic signs. Therefore, the specific needs of individuals with dyslexia on the road should be considered in plans aimed at increasing traffic safety and fluidity.

A timely and accurate acquisition of the information provided by variable message signs (VMS) can be crucial while driving. In the current study, we assess the difficulties of adults with dyslexia acquiring the information shown in VMS and provide evidence to discuss the controversial use of pictograms as potential countermeasures. Twenty-two adults with dyslexia and 22 matched controls completed a simulated driving session. The legibility of 12 VMS was assessed, including six text messages (e.g. "ACCIDENT") and six single pictograms (e.g. the icon for "accident ahead"). On average, participants with dyslexia started reading text messages when they were closer to the VMS. In addition, while approaching text VMS, they dedicated more gazes and manifested worse control of speed. Regarding pictogram VMS, we observed no differences in response distance, accuracy, response duration, or number of gazes. To sum up, the evidence provided reveals that adults with dyslexia, despite potential compensation effects, may still find difficulties reading text messages in VMS (shorter legibility distances, longer reading times, and increased cognitive effort), whereas we found no such differences in the recognition of pictograms (only some difficulties keeping a steady speed). Research on inclusive measures to improve reading in low-skilled or dyslexic drivers must be encouraged.

Prior to using a diagnostic test in a routine clinical setting, the rigorous evaluation of its diagnostic accuracy is essential. The receiver-operating characteristic curve is the measure of accuracy most widely used for continuous diagnostic tests. However, the possible impact of extra information about the patient (or even the environment) on diagnostic accuracy also needs to be assessed. In this paper, we focus on an estimator for the covariate-specific receiver-operating characteristic curve based on direct regression modelling and nonparametric smoothing techniques. This approach defines the class of generalised additive models for the receiver-operating characteristic curve. The main aim of the paper is to offer new inferential procedures for testing the effect of covariates on the conditional receiver-operating characteristic curve within the above-mentioned class. Specifically, two different bootstrap-based tests are suggested to check (a) the possible effect of continuous covariates on the receiver-operating characteristic curve and (b) the presence of factor-by-curve interaction terms. The validity of the proposed bootstrap-based procedures is supported by simulations. To facilitate the application of these new procedures in practice, an R-package, known as npROCRegression, is provided and briefly described. Finally, data derived from a computer-aided diagnostic system for the automatic detection of tumour masses in breast cancer is analysed.

Background Previous research suggested that vigilance may moderate the functioning of other attentional components. However, vigilance is usually neglected when comparing the attentional functioning between groups of clinical and/or healthy participants. New method We combined data from several studies using the Attention Network Test for Interactions and Vigilance (ANTI-V), which includes a vigilance measure plus phasic alertness, orienting, and executive control scores. We estimated, for the first time, the reliability of the vigilance performance indices in the ANTI-V, by analyzing split-half correlations of 10,000 permutations of the trials. In addition, we tested whether a different attentional functioning would be found across the group of healthy participants varying in their vigilance performance, by using a considerably larger sample size (226 participants) than previous studies. Results Vigilance indices were the most reliable among the different attentional scores. Regression models show an inverse relationship between vigilance and phasic alertness and executive control. Comparison with existing methods No previous study has analysed the reliability of the vigilance performance indices in the ANTI-V. In comparison with other ANT variations, the ANTI-V provides a reliable measure of vigilance together with the typical phasic alertness, orienting and executive control scores. In addition, we provide estimates, based on a large sample size, of the magnitude of the link between vigilance and other attentional functions. Conclusions When assessing the multiple functions of attention, the current study highlights the importance of measuring vigilance, which may modulate the functioning of other attentional components, such as phasic alertness or executive control.

The current research shows the advantage of single-word messages in the particular case of variable message signs (VMSs) with a high aspect ratio.Early studies on traffic sign design proposed that pictorial information would advantage equivalent text messages in static signs.We used a driving simulator to present individually 36 VMSs, showing six words (e.g., "congestion") and six danger signs (e.g., congestion traffic sign). In Experiment 1, 18 drivers read aloud the text or orally identified the pictograms as soon as they could correctly do it. In Experiment 2, a different sample of 18 drivers gave a motor response, according to the meaning of the message. We analyzed the legibility distance and accuracy, driving performance (speed variability), and glance behavior.Our results show that single-word messages were associated with better performance (farther reading distances) and required less visual demands (fewer glances and less glancing times) than pictograms.As typical configurations of VMSs usually have a high aspect ratio, and thus allow large character heights, single-word messages can outperform the legibility of pictograms. However, the final advantage of text or pictorial messages would depend on several factors, such as the driver's knowledge of the language and the pictogram set, the use of single or multiple words, the particular design and size of critical details in letters and pictograms, environmental factors, and driver age.Potential applications include the design of VMSs and other devices aimed at displaying text and/or pictograms with a high aspect ratio.

We aimed to compare the diagnostic utility of the STOP-Bang questionnaire for moderate apnoea against the gold standard (type I polysomnography) in a primary care setting.Study of diagnostic utility in primary care. Estimated sample: 85 cases and 85 healthy controls. In convenience sampling, 203 patients were recruited by their physicians at six health centres. Twenty-five were excluded, and 57 women and 121 men, of whom 74 had apnoea-hypopnoea index (AHI) ≥15, were analyzed. STOP-Bang was validated by comparing scores in the same patient with the apnoea-hypopnoea index observed in polysomnography, as a gold standard. Sample size, ROC curve analysis and optimal cut-off points were identified with the easyROC, pROC, and OptimalCutpoints packages.The area under the curve in moderate apnoea (AHI ≥15) of the STOP-Bang was 0.777 (0.667-0.808), with optimal cut-off points different by sex (4 in women and 6 in men). In the cross-validation with k=10, the area under the curve for the STOP-Bang was 0.678.The STOP-Bang presents a diagnostic moderate utility for AHI≥15, but superior to other scales, in a community population. Its performance is more appropriate in women.

Considerable research efforts are currently being devoted to analysing the role that the attentional system plays in determining driving behaviour, with the ultimate objective of reducing the number of attention-related accidents. The present study aims to assess the influence of differences in the functioning of the three attentional networks (executive control, attentional orienting and alerting) when drivers have to deal with some common hazardous situations, for example, when an oncoming car or a pedestrian unexpectedly crosses their trajectory. Multiple measures of participants' attentional functioning were obtained from a computer-based neurocognitive test: the Attention Networks Test for Interactions and Vigilance (ANTI-V). These measures were compared to performance in a driving simulator where different types of hazardous situations were presented. Correlation and linear regression analyses revealed significant associations between individual attentional measures and driving performance in specific traffic situations. In particular, a higher attentional orienting score on the ANTI-V was associated with safer driving in situations where a single precursor anticipated the hazard source, whereas in complex situations with multiple potential hazard precursors, higher attentional orienting scores were associated with delayed braking. Additionally, partial evidence of a relationship between crash occurrence and the functioning of the executive control and the alerting networks was found. Overall, the current research would be helpful to better understand the role that each attentional network (executive control, attentional orienting and alerting) play in safe driving, and thus to develop efficient countermeasures to reduce attention-related crashes. Keywords: Driver distraction; Language: en

Based on Posner's (1994) model of attentional functions, the relationship between age and personal proneness to attention-related errors while driving and the functioning of the 3 attentional networks were explored by means of attentional behavioral measures and self-report data.A sample of 55 drivers was drawn from the general population of Mar del Plata, Buenos Aires, Argentina. The Attention Network Test for Interactions (ANTI) (Callejas et al. 2004) task was used to obtain behavioral measures of the attentional networks, and we used the Attention-Related Driving Error Scale (ARDES) (Ledesma et al. 2010) questionnaire to obtain a self-report measure of attention-related driving errors.Drivers reporting the greatest propensity to experience attention-related errors showed an overall slowdown in performance, less endogenous preparation for high = priority warning signs, and a better response to conflict in the presence of valid cues than drivers less prone to attention-related errors while driving. Older participants showed a slowdown in performance, less endogenous preparation for high-priority warning signs, and worse cognitive control when solving conflict in comparison with younger drivers.We suggest that each group variable, attention-related error proneness and age, shows a particular combination of attentional network functioning that implies different ways of being distracted, which have different practical implications for safe driving. It can be inferred that drivers who are more prone to commit attentional errors while driving run less risk in situations in which they can deal with response conflict in the presence of valid cues because of the particular way in which their attentional networks are combined when a valid cue is present, could serve to compensate, with a better response conflict, their general slowdown and less endogenous preparedness for high-priority signs. It can be inferred that older drivers might show a reduction of the general state of alertness to signs that indicate the presence of a dangerous driving situation and in solving conflict in traffic circumstances.

Introduction The publication of the International Registry of Lung Metastases (IRLM) in 1997 was a turning point in favor of surgical resection of lung metastases. Prognostic groups were defined according to resectability, number of metastases, and disease-free interval. The objective of this study was to determine survival in patients who underwent resection of lung metastases from colorectal carcinoma and to evaluate how applicable the prognostic factors established by the IRLM are in this specific patient group. Patients and Methods Patients with lung metastases from colorectal carcinoma who underwent resection between January 1, 2000, and November 30, 2006, were retrospectively analyzed. Survival was calculated using the Kaplan-Meier method, with log-rank comparisons between groups. Results Survivals at 1, 3, 5, and 6 years was 92%, 75%, 54%, and 43%, respectively. The main finding was that 3-year survival was better in patients who underwent atypical resection of the metastasis (75%) than those who required lobectomy (55%). There were no significant differences in survival in terms of number of lung metastases resected or disease-free interval. Conclusions Survival in patients requiring lobectomy for resection of lung metastases from colorectal carcinoma was worse than in those who underwent atypical resection. The number of metastases and disease-free interval may be questionable prognostic factors in the case of lung metastases from colorectal carcinoma.

In many biomedical applications, interest lies in being able to distinguish between two possible states of a given response variable, depending on the values of certain continuous predictors. If the number of predictors, p, is high, or if there is redundancy among them, it then becomes important to decide on the selection of the best subset of predictors that will be able to obtain the models with greatest discrimination capacity. With this aim in mind, logistic generalized additive models were considered and receiver operating characteristic (ROC) curves were applied in order to determine and compare the discriminatory capacity of such models. This study sought to develop bootstrap-based tests that allow for the following to be ascertained: (a) the optimal number q≤p of predictors; and (b) the model or models including q predictors, which display the largest AUC (area under the ROC curve). A simulation study was conducted to verify the behaviour of these tests. Finally, the proposed method was applied to a computer-aided diagnostic system dedicated to early detection of breast cancer. Copyright © 2008 John Wiley & Sons, Ltd.

Background: In recent years a great number of studies have applied generalised additive models (GAMs) to time series data to estimate the short term health effects of air pollution. Lately, however, it has been found that concurvity—the non-parametric analogue of multicollinearity—might lead to underestimation of standard errors of the effects of independent variables. Underestimation of standard errors means that for concurvity levels commonly present in the data, the risk of committing type I error rises by over threefold. Methods: This study developed a conditional bootstrap methology that consists of assuming that the outcome in any observation is conditional upon the values of the set of independent variables used. It then tested this procedure by means of a simulation study using a Poisson additive model. The response variable of this model is a function of an unobserved confounding variable (that introduces trend and seasonality), real black smoke data, and temperature. Scenarios were created with different coefficients and degrees of concurvity. Results: Conditional bootstrap provides confidence intervals with coverages close to nominal (95%), irrespective of the degree of concurvity, number of variables in the model or magnitude of the coefficient to be estimated (for example, for a concurvity of 0.85, bootstrap confidence interval coverage is 95% compared with 71% in the case of the asymptotic interval obtained directly with S-plus gam function). Conclusions: The bootstrap method avoids the problem of concurvity in time series studies of air pollution, and is easily generalised to non-linear dose-risk effects. All bootstrap calculations described in this paper can be performed using S-Plus gam.boot software.

We present the case of an 8-year-old female patient with bone dysplasia as part of Dyggve-Melchior-Clausen syndrome (DMCS). MRI was used to evaluate the case. In the spine, odontoid apophysis aplasia was found with no ossification nucleus, vertebrae with central hump, disk protrusions, hypertrophy of the posterior common vertebral ligament, and hidden spina bifida at the S4 level. Morphological anomalies were found in the hips both in the proximal femoral epiphysis, which was located excentrically and laterally to the femoral neck, and in the Y-cartilage, which was greatly enlarged. In the knees, anterior crossed ligaments were not seen, although there were some indirect signs that indicated congenital absence, including hypoplasia of the femoral trochlea and the intercondylar notch. There was bilateral medial patellar plicae and asymmetry in the height of the distal femoral and proximal tibial physes, as well as dysplasia of the facets of the patella. In comparison with radiography, MRI provides a much clearer definition of the aspects of bone dysplasia that are related to DMCS, including morphological changes in the soft tissue and cartilage of the spine, hips, and knees. MRI can enhance our understanding of the pathogenesis and evolution of deformities.

We have evaluated reconstruction methods using smooth basis functions in the electron tomography of complex biological specimens. In particular, we have investigated series expansion methods, with special emphasis on parallel computation. Among the methods investigated, the component averaging techniques have proven to be most efficient and have generally shown fast convergence rates. The use of smooth basis functions provides the reconstruction algorithms with an implicit regularization mechanism, very appropriate for noisy conditions. Furthermore, we have applied high-performance computing (HPC) techniques to address the computational requirements demanded by the reconstruction of large volumes. One of the standard techniques in parallel computing, domain decomposition, has yielded an effective computational algorithm which hides the latencies due to interprocessor communication. We present comparisons with weighted back-projection (WBP), one of the standard reconstruction methods in the areas of computational demand and reconstruction quality under noisy conditions. These techniques yield better results, according to objective measures of quality, than the weighted backprojection techniques after a very few iterations. As a consequence, the combination of efficient iterative algorithms and HPC techniques has proven to be well suited to the reconstruction of large biological specimens in electron tomography, yielding solutions in reasonable computation times.

Difficulty attending is a common deficit of euthymic bipolar patients. However, it is not known whether this is a global attentional deficit or relates to a specific attentional network. According to the attention network approach, attention is best understood in terms of three functionally and neuroanatomically distinct networks-alerting, orienting, and executive control. In this study, we explored whether and which of the three attentional networks are altered in euthymic Bipolar Disorder (BD). A sample of euthymic BD patients and age-matched healthy controls completed the Attention Network Test for Interactions and Vigilance (ANTI-V) that provided not only a measure of orienting, executive, and alerting networks, but also an independent measure of vigilance (tonic alerting). Compared to healthy controls, BD patients have impaired executive control (greater interference), reduced vigilance (as indexed by a decrease in the d′ sensitivity) as well as slower overall reaction times and poorer accuracy. Our results show that deficits in executive attention and sustained attention often persist in BD patients even after complete remission of affective symptoms, thus suggesting that cognitive enhancing treatments programmed to improve these deficits could contribute to improve their functional recovery.

The aim of the current study is to develop and obtain valid evidence for a hazard perception test suitable for the Spanish driving population. To obtain valid evidence to support the use of the test, the effect of hazardous and quasi-hazardous situations on the participants' hazard prediction is analyzed and the pattern of results for drivers with different driving experience--that is, learner, novice, and expert drivers and reoffender vs. nonoffender drivers--is compared. Potentially hazardous situations are those that develop without involving any real hazard (i.e., the driver did not actually have to decelerate or make any evasive maneuver to avoid a potential collision). The current study analyzed repeat offender drivers attending compulsory reeducation programs as a result of reaching the maximum number of penalty points on their driving license due to repeated violations of traffic laws.A new video-based hazard perception test was developed, using a total of 20 hazardous situation videos plus 8 quasi-hazardous situation videos. They were selected from 167 recordings of natural hazards in real Spanish driving settings.The test showed adequate psychometric properties and evidence of validity, distinguishing between different types of drivers. Psychometric results confirm a final version of the hazard perception test composed of 11 video clips of hazards and 6 video clips of quasi-hazards, for which an overall Cronbach's alpha coefficient of.77 was obtained. A lack of ability to detect quasi-hazards and distinguish them from hazardous situations was also found for learner, novice, and reoffender drivers. Learner drivers obtained lower average scores than novice and experienced drivers with the hazardous situation videos, and learner drivers obtained lower average scores than experienced drivers with the quasi-hazardous situation videos, suggesting that the ability to correctly identify hazardous traffic situations may develop early by accumulating initial driving experience. However, the ability to correctly identify quasi-hazardous situations may develop later with the accumulation of further driving experience. Developing this ability is also difficult for reoffender drivers.The test has adequate psychometric properties and is useful in distinguishing between learner, novice, and expert drivers. In addition, it is useful in that it analyzes the performance of both safe and unsafe drivers (reoffenders who have already lost their driving license).

CI-980 is a synthetic mitotic inhibitor that binds to the colchicine binding site of tubulin. It demonstrates broad activity against human and murine tumor models and shows no cross resistance with tumor models whose mechanism of resistance is mediated by P-glycoprotein (MDR-1). A phase I study was completed in 25 patients with solid tumors using a 24-hour infusion schedule, with courses repeated every 3 weeks. Eight dose levels were tested between 1.2 and 15.6 mg/m2. The maximum tolerated dose was 14.4 mg/m2. Neutropenia was dose-related but not dose-limiting; thrombocytopenia was infrequent. CNS toxicities were dose-limiting and consisted of dizziness, headache, loss of coordination, loss of consciousness, nervousness, and other symptoms. These events occurred near the end of the infusion and were reversible, usually within 24 hours. One patient who was to be treated at dose level 8 (intended dose was 19.2 mg/m2; actual dose was 15.6 mg/m2) became encephalopathic prior to completion of the infusion. Other adverse events included gastrointestinal toxicities (nausea, vomiting, anorexia, constipation, stomatitis, dyspepsia, bleeding, cheilitis), IV site erythema, fever, and fatigue. A partial response was observed in one patient with colon cancer and reductions in CA-125 levels were observed in 2 patients with ovarian cancer. Pharmacokinetics were linear and dose-proportional. Results indicate high systemic clearance and wide tissue distribution. Mean pharmacokinetic parameter values: T1/2 = 5.52 hours, plasma clearance 1163 mL/min/m2, and Vdss 376 L/m2.

In this preliminary study we assessed the functioning of the different attentional networks in mild cognitive impairment (MCI) patients, taking as theoretical framework the Posner's cognitive neuroscience approach. Two groups of participants were tested in a single short experiment: 20 MCI patients (6 amnestic, 6 non-amnestic and 8 multiple-domain) and 18 healthy matched controls (HC). For attentional assessment we used a version of the Attention Network Test (the ANTI-V) that provided not only a score of the orienting, the executive, and the alerting networks and their interactions, but also an independent measure of vigilance (tonic alerting). The results showed that all subtypes of MCI patients exhibited a selective impairment in the tonic component of alerting, as indexed by a decrease in the d' sensitivity index, and their performance in executive network increased up to the HC group level when phasic alerting was provided by a warning tone. Our findings suggest that a core attentional deficit, especially the endogenous component of alerting, may significantly contribute to the behavioral and cognitive deficits associated with MCI.

The diaphragm is the main muscle involved in ventilation and is supplied exclusively by the phrenic nerves. Congenital defects of the diaphragm muscle or phrenic nerve injury cause diaphragmatic paralysis-eventration. Prognosis and treatment depend on whether involvement is unilateral or bilateral and on the patient's previous clinical status. In addition, the diaphragm is an anatomical barrier between the thoracic and abdominal cavities and is traversed by the esophagus and important vascular and nerve structures. Abnormal dilation of the natural orifices of the diaphragm or loss of its continuity can cause abdominal structures to pass into the chest cavity, an occurrence known as diaphragmatic hernias. According to their etiology, hernias are divided into congenital, acquired and traumatic. Clinical manifestations, prognosis and treatment depend mainly on hernia size and age at diagnosis. Like any muscle, the diaphragm can develop benign or malignant primary tumors. However, diaphragm involvement due to tumors arising in adjacent organs is much more common. The prognosis is good in benign primary tumors and poor in both primary and secondary malignant tumors. This article reviews the main anatomical and physiological characteristics of the diaphragm, routes of surgical access and the most frequent diseases affecting this structure.

The study of sleep deprivation is a fruitful area of research to increase our knowledge of cognitive functions and their neural basis. In the current work, 26 healthy young adults participated in a sleep deprivation study, in which the Attentional Networks Test for Interactions and Vigilance (ANTI-V) was performed at 10 a.m. after a night of normal sleep and again at 10 a.m. after 25.5–27.5 h of total sleep deprivation. The ANTI-V is an experimental task that provides measures of alerting, orienting and executive control attentional functions. Compared with previous versions, the ANTI-V includes a vigilance task, more reliable auditory alerting signals, non-predictive peripheral orienting cues, and also a neutral no-cue condition allowing the analysis of reorienting costs and orienting benefits. Thus, new evidence to evaluate the influence of sleep deprivation on attentional functioning is provided. Results revealed differences in both tonic and phasic alertness after sleep deprivation. Vigilance performance was deteriorated, while a warning tone was more helpful to increase participants' alertness, resulting in slightly faster RT and, in particular, fewer errors. The reorienting costs of having an invalid spatial cue were reduced after sleep loss. No sleep deprivation effect on the executive control measure was found in this study. Finally, since no control group was used, particular precautions were taken to reduce the influence of potential practice effects.

Vigilance could be a crucial aspect of attention that may modulate the functioning of the attentional system. Some behavioural tests, such as the Attention Network Test (ANT), have been developed to obtain an individual index of the three attentional networks (alertness, orientation, and executive control). However, alerting network measures are usually inferred using a phasic alertness task, and some indirect indexes of tonic alertness or vigilance have been proposed but not properly evaluated. The general aim for the present study is to provide the ANT with a direct measure of vigilance and then to analyse the relationship between this measure and other alternative indirect indexes. The obtained results suggest that the proposed new test (ANTI-Vigilance or ANTI-V) is useful to achieve a direct measure of vigilance and could be considered as a new tool available in cognitive, clinical or behavioural neurosciences for analysing vigilance in addition to the usual ANT scores. Other alternative indexes (such as global reaction time and global accuracy averaged across conditions) are only moderately correlated to a direct vigilance measure. As a consequence, although they may be to some extent related to the participants' vigilance level, they could not be used isolatedly as appropriate indexes of vigilance. Also, the role played by these global measures in the ANT task, which have been previously associated with some performance measures in applied areas (such as driving performance), is discussed.

Extending and updating our knowledge concerning drivers' motivational and cognitive processes is of essential importance if we are to apply policies with long-lasting effects. This study presents data from a representative national survey analyzing the Spanish drivers' beliefs about speed, the risks of speeding, the degree of violation of speed-limits and the reasons for speeding. Results indicate that Spanish drivers rate speeding as a serious offence, yet not among the most dangerous ones. All in all, they claim to comply mostly with the speed limits. However, some interesting violation patterns emerge: observance is lower for generic speed limits according to road type (vs. specific limits shown by certain road signs), and particularly in motorways (vs. single carriageways and urban areas). Risk perception and reasons for speeding emerge as the main factors predicting the levels of speed violations reported. Results suggest that any effective intervention strategy should consider such factors, namely the link between speed, road safety, and drivers' specific reasons for speeding.

This research aims to analyse how drivers integrate the information provided by traffic signs with their general goals (i.e. where they want to go). Some previous studies have evaluated the comparative advantages of obligatory and prohibitory traffic signs using a judgement task. In this work, a new experimental task with greater similarity to driving situations is proposed. Participants imagine they are driving a vehicle and must make right or left turn manoeuvres according to a previously indicated objective and the information from obligatory and prohibitory traffic signs. Eighty-two participants took part in two different experiments. According to the results, an obligatory traffic sign is associated with faster and more accurate responses only when the participant’s initial objective is allowed. When the initial objective was not allowed, an advantage in accuracy was observed with prohibitory traffic signs and there was no significant difference in reaction time between the two types of sign. These results suggest that having an obligatory traffic sign may facilitate a correct response when the driver’s goal is effectively allowed, whereas a prohibitory traffic sign could be more effective in preventing error when the driver has a not-allowed goal in mind. However, processing a prohibitory sign requires an extra inference (i.e. deciding which is the allowed manoeuvre), and thus the potential advantage in reaction time of the prohibitory sign may disappear. A second experiment showed that the results could not be explained by a potential congruency effect between the location (left or right) of the road signs and the position of the key or the hand used to respond (such as the Simon effect or the spatial Stroop effect). Also, an increase in the difficulty of the task (using an incongruent hand to respond) affected performance more strongly in experimental conditions that required making inferences. This made the advantage of the obligatory sign over the prohibitory sign in this condition more noteworthy. The evidence gathered in the current study could be of particular interest in some applied research areas, such as the assessment of road traffic signalling strategies or the ergonomic design of GPS navigation systems.

A key issue for the good performance of the penalty point system is that drivers achieve a proper understanding of its philosophy and objectives. If this enforcement system is valuated as an effective and socially beneficial measure, there is a higher probability that drivers will show a stronger and permanent change. On the contrary, if the penalty point system is perceived as a tax-collecting measure, it would be very difficult for its principal aims to be achieved. From a national telephone survey conducted on a sample of 2.014 respondents, the present study analyses drivers' appraisal of the Spanish penalty point system. The results show that drivers' evaluation of the system is very positive and also that they have high expectations for its success. Moreover, beyond a mere repressive or tax-collecting view of the penalty point system, drivers state that its main goal is to increase awareness and improve road safety.

On July 1, 2006 a penalty point system was introduced in Spain. One year later, a reduction of 14.3% was observed in road traffic casualties, whilst the previous year that figure was 4.9%. A national telephone survey was conducted on a sample of 2.014 respondents to explore the drivers' point of view about the influence of the penalty point system on driving behaviour. Results point to a moderate behavioural change, mainly in relation to speeding and mobile phone misuse, this change being slightly more intense in drivers who were fined during the previous year. Awareness of road traffic accidents increased in around 40% of drivers. Lastly, mobility loss stands out as the most worrying and presumably most influential consequence of driving license loss.

Recently, the generalized additive models (GAMs) have been presented as a novel statistical approach to distinguish lesion/non-lesion in computer-aided diagnosis (CAD) systems. In this paper, we present an extension of the GAM that allows for the introduction of factors and their interactions with continuous variables, for reducing false positives in a CAD system for detecting clustered microcalcifications in digital mammograms. The results obtained have shown an increase in the sensitivity from 83.12% to 85.71%, while the false positive rate was drastically reduced from 1.46 to 0.74 false detections per image.

In many biomedical studies, interest is often attached to calculating effect measures in the presence of interactions between two continuous exposures. Traditional approaches based on parametric regression are limited by the degree of arbitrariness involved in transforming these exposures into categorical variables or imposing a parametric form on the regression function. In this paper, we present: (a) a flexible non-parametric method for estimating effect measures through generalized additive models including interactions; and (b) bootstrap techniques for (i) testing the significance of interaction terms, and (ii) constructing confidence intervals for effect measures. The validity of our methodology is supported by simulations, and illustrated using data from a study of possible risk factors for post-operative infection. This application revealed a hitherto unreported effect: for patients with high plasma glucose levels, increased risk is associated, not only with low, but also with high percentages of lymphocytes. Copyright © 2005 John Wiley & Sons, Ltd.

The generalized additive, model (GAM) is a powerful and widely used tool that allows researchers to fit, non-parametrically, the effect of continuous predictors on a transformation of the mean response variable. Such a transformation is given by a so-called link function, and in GAMs this link function is assumed to be known. Nevertheless, if an incorrect choice is made for the link, the resulting GAM is misspecified and the results obtained may be misleading. In this paper, we propose a modified version of the local scoring algorithm that allows for the non-parametric estimation of the link function, by using local linear kernel smoothers. To better understand the effect that each covariate produces on the outcome, results are expressed in terms of the non-parametric odds ratio (OR) curves. Bootstrap techniques were used to correct the bias in the OR estimation and to construct point-wise confidence intervals. A simulation study was carried out to assess the behaviour of the resulting estimates. The proposed methodology was illustrated using data from the AIDS Register of Galicia (NW Spain), with a view to assessing the effect of the CD4 lymphocyte count on the probability of being AIDS-diagnosed via Tuberculosis (TB). This application shows how the link's flexibility makes it possible to obtain OR curve estimates that are less sensitive to the presence of outliers and unusual values that are often present in the extremes of the covariate distributions.