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Vascular endothelial growth factor (VEGF) has been shown to play a major role in intraocular neovascularisation in ischaemic retinal diseases. The aim of this study was to evaluate the concentration of VEGF in vitreous, aqueous and epiretinal membranes of diabetic and non-diabetic patients, with other pathological conditions requiring surgical intervention. Higher VEGF concentration were found in samples from the eyes of diabetic patients versus other pathologies as well as in epiretinal membranes versus the other eye compartments in diabetic patients. However, high VEGF levels were also found in retinal detachment and proliferative vitreoretinopathy of non-diabetic patients. We concluded that VEGF is produced locally and plays a fundamental, but not specific, role in diabetic retinal neovascularisation and proliferation.

We compared the performance of skilled drummers with that of nondrummers and nonmusicians in the Simon and spatial stimulus—response compatibility (SRC) tasks to investigate whether and to what extent spatial performance can be modified by motor behaviors acquired in real life. Drummers were chosen because, compared with other musicians and the general population, their efficient performance depends mainly on the processing of spatial information. Although the Simon effect was equivalent for the three groups, the spatial SRC effect was less pronounced in drummers. The advantage was present even when feet were used as responding effectors, suggesting a central locus of the effect. These results suggest that spatial stimulus—response translations are influenced by real-life motor training, with drummers’ training speeding up the intentional stimulus—response translations when stimulus and response locations are on opposite sides.

In this study we investigated in a Simon-like task whether task-irrelevant spatial information, delivered by centrally presented patterns, interfered with response selection in the same way as laterally presented stimuli. Second, we asked whether such interference was equal for different kinds of stimuli. Participants were required to respond to the colour of two framed squares, two arrows, or two schematic eyes by pressing one of two lateralized response keys. The results consistently show that the Simon effect occurs independently of the nature of the stimulus, as classically reported for lateralized stimuli. Response times were influenced by the direction and frame-relative position of the stimuli, being faster for responses corresponding to the direction indicated by the stimuli than for noncorresponding responses regardless of stimulus types. Contrary to findings with lateralized nondirectional stimuli, such an effect increased with increasing RTs indicating that for centrally presented patterns the extraction of spatial information is time consuming. Spatial location has been demonstrated to be automatically coded with a large variety of stimuli, even in situations in which it is irrelevant to the task to be performed (e.g., Tsal & Lavie, 1993). The effects of irrelevant spatial codes emerge very clearly in the Simon task in which participants are presented with two different lateralized patterns (i.e., placed in the periphery of the visual field) and are required to press the right-side key in response to one pattern, and the left-side key in response to the other (Simon & Rudell, 1967; see Hommel & Prinz, 1997; Lu & Proctor, 1995, for reviews). Even though participants are clearly instructed to select the response exclusively on the basis of the relevant nonspatial stimulus dimension, irrelevant information concerning stimulus location is processed. As a consequence, faster responses are made when the position of the stimulus and the position of the response key are located on the same side (right-right or left-left; i.e., corresponding S-R pairings) compared to when they are positioned differently (stimulus on the right side and response on the left side, or vice versa; i.e., noncorresponding S-R pairings). Recent studies seem to suggest that stimulus position is not the only dimension capable of automatically activating a response spatial code that influences performance. For instance, central arrows have been shown to influence both voluntary (e.g., Posner, 1980) and automatic (e.g., Danziger, Kingston, & Ward, 2001; Eimer, 1997; Hommel, Pratt, Colzato, & Godijn, 2001; Ristic, Friesen, & Kingstone, 2002; Tipples, 2002) orienting of visual attention. Furthermore, it seems well established that centrally presented arrows (i.e., presented at central fixation) can produce the Simon effect (e.g., Masaki, Takasawa, & Yamazaki, 2000). This result is not surprising since arrows are commonly used to convey spatial information and have therefore acquired a directional meaning. Gaze direction is another stimulus shown to deliver spatial information (e.g., Ansorge, 2003b; Zorzi, Mapelli, Rusconi, & Umilta, 2003; Langton & Bruce, 2000). However, not only does it provide the observer with directional spatial information, but it can communicate different types of crucial information such as the focus of attention, interest, emotions, and intentions of others (e.g., Baron-Cohen & Cross, 1994; Emery, 2000). Eye direction is also capable of automatically and reflexively triggering the orienting behaviour of the observer (e.g., Driver et al., 1999; Friesen & Kingstone, 1998; Friesen, Ristic, & Kingstone, 2004; Langton & Bruce, 1999). All this makes gaze direction biologically relevant for survival and the eyes a key social cue for understanding the mind of others (Baron-Cohen, 1995). Recently, Zorzi et al. (2003) showed that the direction of eye-like stimuli elicits a specific spatial code, independent from the stimulus spatial position, which can influence lateralized manual responses. …

Recent evidence assigns integrins and metalloproteinases (MMPs) an important role in regulating tumor cell progression. Here, we demonstrate that 3-O-methylfunicone (OMF), a secondary metabolite produced by Penicillium pinophilum, affects cell proliferation and motility of breast cancer MCF-7 cells, downregulating avb5 integrin, and inhibiting MMP-9 secretion. This effect was absent when the non-tumoral MCF-10 cell line was used. Inhibition of cell motility was also associated to modifications in cell shape and in the distribution of tubulin fibers of OMF-treated MCF- 7 cells. In addition, a possible effect on survivin and hTERT was also investigated. We found that OMF strongly inhibits survivin and hTERT gene expression. The results of this study indicate that OMF-induced inhibition of cell motility may be mediated through the modulation of avb5 integrin and MMP-9secretion. In addition, the inhibition of typical markers of tumor progression such as hTERT and survivin in MCF-7 and their inactivity towards MCF10 provide strong evidence for a potential use of OMF in anticancer therapy Recent evidence assigns integrins and metalloproteinases (MMPs) an important role in regulating tumor cell progression. Here, we demonstrate that 3-O-methylfunicone (OMF), a secondary metabolite produced by Penicillium pinophilum, affects cell proliferation and motility of breast cancer MCF-7 cells, downregulating αvβ5 integrin, and inhibiting MMP-9 secretion. This effect was absent when the non-tumoral MCF-10 cell line was used. Inhibition of cell motility was also associated to modifications in cell shape and in the distribution of tubulin fibers of OMF-treated MCF-7 cells. In addition, a possible effect on survivin and hTERT was also investigated. We found that OMF strongly inhibits survivin and hTERT gene expression. The results of this study indicate that OMF-induced inhibition of cell motility may be mediated through the modulation of αvβ5 integrin and MMP-9 secretion. In addition, the inhibition of typical markers of tumor progression such as hTERT and survivin in MCF-7 and their inactivity towards MCF10 provide strong evidence for a potential use of OMF in anticancer therapy. © 2007 Wiley-Liss, Inc.

In the present study, we examined the pupillary response of White participants who were asked to tell the truth or lie to White or Black partners. Research on cues to deception has assumed that lying is more cognitively demanding that truth telling. In line with this assumption, previous studies have shown that lying is associated with greater pupil dilation, a behavioral cue that typically manifests itself under conditions of stress or cognitive effort. In accordance with these results, we predicted greater pupil dilation when lying than when telling the truth. Furthermore, pupil dilation was expected to be greater when responding to White than Black partners. Finally, we hypothesized that pupil dilation would be greater when lying to White than Black partners. Participants were instructed to answer a set of questions, half truthfully and half deceptively. They were led to believe that White vs. Black partners (one male and one female) would ask the questions via computer connection. Indeed, we used feminine and masculine synthetic voices. Pupil dilation was assessed with a remote eye-tracking system. Results provided support for the first two hypotheses. However, the predicted interaction between race of partners and truth status of message (lying vs. telling the truth) was nonsignificant. Our findings highlight the importance of considering race in the study of truthful and deceptive communications.

Previous research has shown an effect of handle-response correspondence on key-press responses when participants judged the upright or inverted orientation of photographed one-handled graspable objects. In three experiments, we explored whether this effect still holds for symmetric graspable objects that are usually grasped by two hands (i.e. two-handled objects; e.g. shears). In Experiments 1 and 2, participants were required to perform a between-hand response in order to categorize cooking or amusement objects appearing as grasped from either an allocentric (Experiment 1) or an egocentric perspective (Experiment 2). In Experiment 3, they were required to perform a within-hand response to categorize the same stimuli appearing as grasped from an egocentric perspective. Across all three experiments, results showed that categorization was more difficult when the objects were displayed as grasped on the opposite side than the response rather than on the same side. We discuss the implications of these results for theories of action potentiation and spatial coding and suggest that different mechanisms may be recruited depending on the required action (i.e. response mode).

Summary Background Current treatment for metastatic pancreatic ductal adenocarcinoma includes combination chemotherapy, such as FOLFIRINOX or nab-paclitaxel plus gemcitabine. We investigated the activity of a novel four-drug regimen, consisting of cisplatin, nab-paclitaxel, capecitabine, and gemcitabine, compared with nab-paclitaxel plus gemcitabine, in the PACT-19 trial. Methods This single-centre, randomised, open-label, phase 2 trial was done in San Raffaele Hospital in Italy. We enrolled patients aged 18–75 years with pathologically confirmed stage IV pancreatic ductal adenocarcinoma who had received no previous chemotherapy and had Karnofsky performance status of at least 70. Patients were randomly assigned (1:1) by computer-generated permutated block randomisation (block size of four) stratified by baseline concentration of carbohydrate antigen 19-9 to PAXG (cisplatin 30 mg/m 2 , nab-paclitaxel 150 mg/m 2 , and gemcitabine 800 mg/m 2 on days 1 and 15 and oral capecitabine 1250 mg/m 2 on days 1–28 every 4 weeks), or nab-paclitaxel and gemcitabine alone (nab-paclitaxel 125 mg/m 2 and gemcitabine 1000 mg/m 2 on days 1, 8, and 15 every 4 weeks). The primary endpoint was the proportion of patients who were progression-free at 6 months, analysed in the intention-to-treat population. Data cutoff was on March 31, 2018. The safety population included all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01730222, and is now closed. Findings Between April 22, 2014, and May 30, 2016, we randomly assigned 83 patients to treatment: 42 patients to PAXG and 41 patients to nab-paclitaxel plus gemcitabine. At 6 months, 31 (74%, 95% CI 58–86) of 42 patients in the PAXG group were alive and free from disease progression compared with 19 (46%, 31–63) of 41 patients in the nab-paclitaxel plus gemcitabine group. The most frequent grade 3 adverse events were neutropenia (12 [29%] of 42 in the PAXG group vs 14 [34%] of 41 in the nab-paclitaxel plus gemcitabine group), anaemia (nine [21%] vs nine [22%]), and fatigue (seven [17%] vs seven [17%]). The most common grade 4 adverse event was neutropenia (five [12%] in the PAXG group vs two [5%] in the nab-paclitaxel plus gemcitabine group). Two (5%) treatment-related deaths occurred in the nab-paclitaxel plus gemcitabine group compared with none in the PAXG group. Interpretation Despite the small sample size, our findings suggest that the PAXG regimen warrants further investigation in a phase 3 trial in patients with metastatic pancreatic ductal adenocarcinoma. Funding Celgene.

Patients with borderline (BL) or locally advanced (LA) pancreatic adenocarcinoma are usually treated with primary chemotherapy (CT), followed by resection when feasible. Scanty data are available about the criteria to candidate patients to resection after CT.Between 2002 and 2016 overall 223 patients diagnosed with BL or LA pancreatic adenocarcinoma were primarily treated with Gemcitabine combination (4-drugs or nab-paclitaxel-gemcitabine) for 3-6 months followed by surgery and/or chemoradiation. Resection was carried out when radical resection could be predicted by imaging studies and intraoperative findings. The prognostic value of both pre-treatment factors and treatment response was retrospectively evaluated, searching for criteria that could improve the selection of patients for surgery.Median survival (MS) for the whole population was 18.3 months. Surgical resection was carried out in 61 patients; MS in resected patients was significantly longer (30.0 months) as compared with 162 non-resected patients (16.5 months) (P 0.00001). According to response criteria, 48% had a radiological partial response, 47% a stable disease and 5% a disease progression); CA19.9 response (reduction 50%) was obtained in 77.8% of patients. Among resected patients, neither pre-treatment factors, including BL/LA distinction, nor radiological response, were able to prognosticate survival differences. Survival of resected patients having no CA19.9 response was significantly lower as compared with responders (MS 15.0 versus 31.5 months, P = 0.04), and was similar to non-responders patients that did not undergo resection (MS 10.9 months, P= 0.25). Multivariate analysis carried out on the overall population, showed that Karnofsky performance status, T3-T4 status, resection and CA19.9 response were independent prognostic factors, while radiological response, BL/LA distinction and baseline CA19.9 had not significant influence on survival.CA19.9 response may allow a better selection of patients who will benefit from resection after primary CT for BL or LA pancreatic adenocarcinoma.

Background New therapies are needed for pancreatic cancer. Objective To determine the feasibility and safety of a new endoscopic treatment. Secondary endpoints were to determine effects on tumor growth measured with CT scan and to find the overall survival. Design A cohort study of patients with local progression of advanced pancreatic adenocarcinoma after neoadjuvant therapy. The cryotherm probe (CTP), a flexible bipolar device that combines radiofrequency with cryogenic cooling, was used under EUS guidance. Setting San Raffaele Hospital, Milan, Italy; University Medical Center, Hamburg-Eppendorf, Germany. Patients A total of 22 patients (male/female 11/11; mean age 61.9 years) were enrolled from September 2009 to May 2011. Intervention Radiofrequency heating: 18 W; pressure for cooling: 650 psi (Pounds per Square Inch); application time: depending on tumor size. Main Outcome Measurements Feasibility was evaluated during the procedure. A clinical and radiologic follow-up was planned. Results The CTP was successfully applied in 16 patients (72.8%); in 6 it was not possible because of stiffness of the GI wall and of the tumor. Amylase arose in 3 of 16 patients; none had clinical signs of pancreatitis. Late complications arose in 4 cases: 3 were mostly related to tumor progression. Median postablation survival time was 6 months. A CT scan was performed in all patients, but only in 6 of 16 was it possible to clearly define the tumor margins after ablation. In these patients, the tumor appeared smaller compared with the initial mass (P = .07). Limitations Small sample of patients, difficulty of objectifying the size of the ablated zone by CT scan. Conclusion EUS-guided CTP ablation is feasible and safe. Further investigations are needed to demonstrate progression-free survival and local control.

Scientific reports 6, 21706 (2016). doi:10.1038/srep21706, Published by Nature Publishing Group, London

Background: Nab-paclitaxel-gemcitabine combination significantly improved overall survival over gemcitabine in metastatic pancreatic adenocarcinoma. A phase 1b trial was performed (ClinicalTrials.gov number, NCT01730222) to determine the recommended phase 2 dose (RP2D) of nab-paclitaxel in combination with cisplatin, capecitabine, and gemcitabine at fixed dose (800, 30, and 1250 mg m(-2) every 2 weeks, respectively; PAXG regimen). Methods: Nab-paclitaxel doses were escalated from 100 (level one) to 125 (level two) and 150 mg m(-2) (level three) every 2 weeks in cohorts of 3-6 patients with pathologically confirmed unresectable or borderline resectable pancreatic adenocarcinoma. Results: Between Dec 2012 and Apr 2014, 24 patients were enroled (3 at level one, 5 at level two, 16 at level three) and received 117 cycles of PAXG. No dose-limiting toxicity occurred and level three was the RP2D. At this dose, nab-paclitaxel dose-intensity was 91%. Worse per patient grade 3/4 toxicity were neutropenia 25/31%; fatigue 19%; anaemia and hand-foot syndrome 12%, nausea 6%, and febrile neutropenia 6%. A partial response (PR) was observed in 16 (67%) and stable disease (SD) in 8 patients (33%). Among 21 patients with a baseline positive positron emission tomography (PET) scan, a complete metabolic response was observed in 9 (43%), PR in 10 (48%), SD in 2. CA19-9 decreased by >= 49% in all the 19 patients with elevated basal value. Six patients were resected after chemotherapy. Progression-free survival at 6 months (PFS-6) was 96%. Conclusions: The RP2D of nab-paclitaxel in the PAXG regimen was 150 mg m(-2) every 2 weeks. The preliminary results are promising and warrant further exploration. ZB 0 Z8 0 ZR 0 ZS 0

Background The aim of this study was to prospectively compare the diagnostic performance of magnetic resonance imaging (MRI), multidetector computed tomography (MDCT) and endoscopic ultrasonography (EUS) in the preoperative locoregional staging of gastric cancer. Methods This study had Institutional Review Board approval, and informed consent was obtained from all patients. Fifty-two patients with biopsy-proven gastric cancer underwent preoperative 1.5-T MRI, 64-channel MDCT and EUS. All images were analysed blind, and the results were compared with histopathological findings according to the seventh edition of the TNM classification. After the population had been divided on the basis of the local invasion (T1-3 vs T4a-b) and nodal involvement (N0 vs N+), sensitivity, specificity, positive and negative predictive value, and accuracy were calculated and diagnostic performance measures were assessed using the McNemar test. Results For T staging, EUS showed higher sensitivity (94 %) than MDCT and MRI (65 and 76 %; p = 0.02 and p = 0.08). MDCT and MRI had significantly higher specificity (91 and 89 %) than EUS (60 %) (p = 0.0009 and p = 0.003). Adding MRI to MDCT or EUS did not result in significant differences for sensitivity. For N staging, EUS showed higher sensitivity (92 %) than MRI and MDCT (69 and 73 %; p = 0.01 and p = 0.02). MDCT showed better specificity (81 %) than EUS and MRI (58 and 73 %; p = 0.03 and p = 0.15). Conclusions Our prospective study confirmed the leading role of EUS and MDCT in the staging of gastric cancer and did not prove, at present, the value of the clinical use of MRI.

There is evidence suggesting that viewing hands triggers automatic access to the Body Structural Description, a visual-spatial representation of human body parts configuration. Hands, however, have a special representational status within the brain because of their significance for action and cognition. We tested whether feet, less important in gestural and object-directed action, would similarly show automatic access to the Body Structural Description. Positive evidence of that would be finding a Sidedness effect (Ottoboni et al. J Exp Psychol Hum Percept Perform 31:778–789, 2005), a Simon-like paradigm previously used to study automatic hand recognition. This effect demonstrates that processing hands generates spatial codes corresponding to the side of the body on which the hand would be located within the Body Structural Description map. Feet were shown with toes pointing upwards (Experiment 1), without any connection to the ankle and the leg (Experiment 2) and with toes pointing downwards (Experiment 3). Results revealed a Sidedness effect in both Experiments 1 and 3: spatial compatibility occurred according to the side of the body that each foot would assume within the Body Structural Description. In Experiment 2, as already found in stimuli similarly featured, no effect emerged, due to the lack of the necessary anatomical links connecting the foot to a body. Results suggest that body parts with variable degrees of significance for action and cognition can access automatically the Body Structural Description hence reinforcing the hypothesis of its pure visuo-spatial nature.

A variety of studies have shown action- and object-related visuo-motor priming in behavioural tasks. The peculiarity of this study lies in using a hand-cued line bisection task to explore the main properties of the motor effects evoked by action and object processing. In five experiments it is shown that flanking a line (thin vs. thick line) with images of hands (biological vs. non-biological hand) representing different actions (power vs. precision grip) biases performance towards the action more compatible with the object (power grip - thick line, precision grip - thin line). This effect is larger for the precision grip than for the power grip suggesting a functional rather than manipulative activation. In addition, the effect is larger for the biological than for the non-biological hand. We suggest that this paradigm could be potentially useful for neuropsychological studies as well as for addressing unsolved issues of embodied theories of cognition.

Background: At the time of upfront treatment failure, over half of the patients with advanced pancreatic cancer are candidates for further treatment. Methods: Patients with metastatic gemcitabine-resistant pancreatic cancer were treated with mitomycin 8 mg/m2 on day 1, ifosfamide 2,500 mg/m2 and mesna 3,000 mg/m2 on days 1–3 every 28 days until progressive disease. A positive responder was defined as a patient who was progression free at 6 months from trial enrolment. According to the Fleming design, a sample size of 34 patients was estimated assuming p0 = 0.05 and p1 = 0.20. Results: Between May 2006 and December 2007, 21 patients (median age 56 years; median Karnofsky performance score 80) were enrolled. One patient died before receiving any treatment. Eighteen patients interrupted chemotherapy due to progressive disease (n = 15), toxicity (n = 2) or refusal (n = 1). Grade >2 toxicity consisted of neutropenia in 80% of patients, thrombocytopenia and fatigue in 20% and anemia in 10%. Only 1 patient was progression free at 6 months (5%). One patient had a partial response (5%) and 2 patients had stable disease (10%). Median survival was 3.7 months. Conclusion: Based on the poor outcome observed and on the high level of grade 3–4 toxicity, the trial was prematurely stopped and the mitomycin and ifosfamide regimen was considered insufficiently active in gemcitabine-pretreated advanced pancreatic cancer.

Objective Celiac artery compression syndrome (CACS) is an unusual condition caused by abnormally low insertion of the median fibrous arcuate ligament and muscular diaphragmatic fiber resulting in luminal narrowing of the celiac trunk. Surgical treatment is the release of the extrinsic compression by division of the median arcuate ligament overlying the celiac axis and skeletonization of the aorta and celiac trunk. The laparoscopic approach has been recently reported for single cases. Percutaneous transluminal angioplasty (PTA) and stenting of the CA alone, before or after the surgical relief of external compression to the celiac axis, has also been used. We report our 7-year experience with the laparoscopic management of CACS caused by the median arcuate ligament. Methods Between July 2001 and May 2008, 16 patients (5 men; mean age, 52 years) were treated. Diagnosis was made by duplex ultrasound scan and angiogram (computed tomography [CT] or magnetic resonance). The mean body mass index of the patients was 21.2 kg/m 2 . One patient underwent laparoscopic surgery after failure of PTA and stenting of the CA, and two patients after a stenting attempt failed. Results All procedural steps were laparoscopically completed, and the celiac trunk was skeletonized. The laparoscopic procedures lasted a mean of 90 minutes. Two cases were converted to open surgery for bleeding at the end of the operation when high energies were used. The postoperative course was uneventful. Mean postoperative hospital stay was 3 days. On follow-up, 14 patients remained asymptomatic, with postoperative CT angiogram showing no residual stenosis of the celiac trunk. One patient had restenosis and underwent aortoceliac artery bypass grafting after 3 months. Another patient had PTA and stenting 2 months after laparoscopic operation. All patients reported complete resolution of symptoms at a mean follow-up of 28.3 months. Conclusions The laparoscopic approach to CACS appears to be feasible, safe, and successful, if performed by experienced laparoscopic surgeons. PTA and stenting resulted in a valid complementary procedure only when performed after the release of the extrinsic compression on the CA. Additional patients with longer follow-up are needed.

The aim of this study was to assess the maximum tolerated dose (MTD) of an intensified PEFG regimen administered every 14 days to patients with Stage III or metastatic pancreatic adenocarcinoma. Twenty-nine patients received fixed doses of both epirubicin (30 mg/m(2)) and 5-fluorouracil (200 mg/m(2)/day on Days 1-14) and of escalating doses of cisplatin and gemcitabine. The MTD was cisplatin 30 mg/m(2) and gemcitabine 800 mg/m(2). With respect to classical PEFG, intensified regimen potentially improved the dose-intensity of both cisplatin and epirubicin by 50 percent and of gemcitabine by 33 percent, reduced Grade 3-4 haematological toxicity and the number of outpatient accesses.

Limited information on salvage treatment in patients affected by pancreatic cancer is available. At failure, about half of the patients present good performance status ( PS) and are candidate for further treatment. Patients > 18 years, PS >= 50, with metastatic pancreatic adenocarcinoma previously treated with gemcitabine- containing chemotherapy, and progression- free survival ( PFS) < 12 months received a combination of raltitrexed ( 3 mgm (-2)) and oxaliplatin ( 130 mgm (-2)) every 3 weeks until progression, toxicity, or a maximum of six cycles. A total of 41 patients received 137 cycles of chemotherapy. Dose intensity for both drugs was 92% of the intended dose. Main grade 42 toxicity was: neutropenia in five patients ( 12%), thrombocytopenia, liver and vomiting in three ( 7%), fatigue in two ( 5%). In total, 10 patients ( 24%) yielded a partial response, 11 a stable disease. Progression- free survival at 6 months was 14.6%. Median survival was 5.2 months. Survival was significantly longer in patients with previous PFS 46 months and in patients without pancreatic localisation. A clinically relevant improvement of quality of life was observed in numerous domains. Raltitrexed oxaliplatin regimen may constitute a treatment opportunity in gemcitabine- resistant metastatic pancreatic cancer. Previous PFS interval may allow the identification of patients who are more likely to benefit from salvage treatment.

A variety of studies showed that participants are facilitated when responding to graspable objects, while it has not been fully investigated what happens during interactions with graspable objects that are potentially dangerous. The present study focuses on the mechanisms underlying the processing of dangerous objects. In two experiments, we adopted a paradigm that has never been employed in this context, a bisection task. The line was flanked by objects belonging to different categories. We explored the sensitivity to the distinction between neutral and dangerous objects, by measuring whether the performance was biased toward a specific object category. In Experiment 1 both teenagers and adults bisected lines flanked by dangerous and neutral graspable objects, and they misperceived the line midpoint toward the neutral graspable object or, stated differently, on the opposite side of the dangerous graspable object. In Experiment 2 adults bisected lines flanked by dangerous and neutral objects matched on graspability (both graspable and ungraspable, Experiment 2a), or by graspable and ungraspable objects matched on dangerousness (both neutral and dangerous, Experiment 2b). Results confirmed the finding of Experiment 1, but also indicated that participants misperceived the line midpoint toward the ungraspable object when it was presented, being it dangerous or not. This evidence demonstrated sensitivity to object dangerousness maintained across lifespan. The emergence of aversive affordances evoked by dangerous graspable objects strenghtens the importance to consider graspability in the investigation of dangerous objects. Possible neural mechanisms involved in the processing of dangerous graspable objects are discussed.

We investigated whether and how comprehending sentences that describe a social context influences our motor behaviour. Our stimuli were sentences that referred to objects having different connotations (e.g., attractive/ugly vs. smooth/prickly) and that could be directed towards the self or towards “another person” target (e.g., “The object is ugly/smooth. Bring it to you/Give it to another person”). Participants judged whether each sentence was sensible or non-sensible by moving the mouse towards or away from their body. Mouse movements were analysed according to behavioral and kinematics parameters. In order to enhance the social meaning of the linguistic stimuli, participants performed the task either individually (Individual condition) or in a social setting, in co-presence with the experimenter. The experimenter could either act as a mere observer (Social condition) or as a confederate, interacting with participants in an off-line modality at the end of task execution (Joint condition). Results indicated that the different roles taken by the experimenter affected motor behaviour and are discussed within an embodied approach to language processing and joint actions.

Several studies suggest that numerical and spatial representations are intrinsically linked. Recent findings demonstrate that also motor actions interact with number magnitude processing, showing a motor-to-semantic effect. The current study assesses whether calculation processes can be modulated by motions performed with the whole body. Participants were required to make additions or subtractions while performing (on-line condition) or after having experienced (off-line condition) an ascending or descending motion through a passive (i.e., taking the elevator) or an active (i.e., taking the stairs) mode. Results show a congruency effect between the type of calculation and the direction of the motion depending on: a) the off-line or on-line condition, b) the passive or active mode and c) the real or imagined task. Implications of the results for an embodied and grounded perspective view will be discussed.

Cancer vaccines have recently been shown to induce some clinical benefits. The relationship between clinical activity and anti-vaccine T cell responses is somewhat controversial. Indeed, in many trials it has been documented that the induction of vaccine-specific T cells exceeds the clinical responses observed. Here, we evaluate immunological and clinical responses in 23 MAGE-A3+ melanoma patients treated with autologous lymphocytes genetically engineered to express the tumor antigen MAGE-A3 and the viral gene product thymidine kinase of the herpes simplex virus (HSV-TK). HSV-TK was used as safety system in case of adverse events and as tracer antigen to monitor the immune competence of treated patients. The increase of anti-TK and anti-MAGE-A3 T-cells after vaccination was observed in 90 and 27% of patients, respectively. Among 19 patients with measurable disease, we observed a disease control rate of 26.3%, with one objective clinical response, and four durable, stable diseases. Three patients out of five with no evidence of disease (NED) at the time of vaccination remained NED after 73+, 70+ and 50+ months. Notably, we report that only patients experiencing MAGE-A3-specific immune responses showed a clinical benefit. Additionally, we report that responder and non-responder patients activate and expand T cells against the tracer antigen TK in a similar way, suggesting that local rather than systemic immune suppression might be involved in limiting clinically relevant antitumor immune responses. OI bregni, marco/0000-0002-3789-1199

An important challenge of embodied theories is to explain the comprehension of abstract sentences. The aim of the present study was to scrutinize the role of the motor cortex in this process. We developed a new paradigm to study the abstract-concrete dimension by combining concrete (i.e., action-related) and abstract (i.e., non-action-related) verbs with nouns of graspable and non-graspable objects. Using these verb-noun combinations we performed a Transcranial Magnetic Stimulation (TMS) on the left primary motor cortex while participants performed a sentence sensibility task. Single-TMS pulses were delivered 250ms after verb or noun presentation in each of four combinations of abstract and concrete verbs and nouns. To evaluate cortico-spinal excitability we registered the electromyographic activity of the right first dorsal interosseous muscle. As to verb-noun integration, analysis of motor evoked potentials (MEPs) after TMS pulse during noun presentation revealed greater peak-to-peak amplitude in phrases containing abstract rather than concrete verbs. Response times were also collected and showed that compatible (Concrete-Concrete and Abstract-Abstract) combinations were processed faster than mixed ones; moreover in combinations containing concrete verbs, participants were faster when the pulse was delivered on the first word (verb) than on the second one (noun). Results support previous findings showing early activation of hand-related areas after concrete verbs processing. The prolonged or delayed activation of the same areas by abstract verbs will be discussed in the framework of recent embodied theories based on multiple types of representation, particularly theories emphasizing the role of different acquisition mechanisms for concrete and abstract words (Borghi and Cimatti, 2009,2012).

Gaze direction and facial expressions are critical components of face processing and have been shown to influence attention deployment. We investigated whether gaze direction (direct vs. averted) combined with a neutral or angry expression modulates the deployment of attentional resources over time. In a rapid serial visual presentation (RSVP) paradigm participants had to decide the gender of a neutral or an angry target face with direct or averted gaze (T1) and then to judge the orientation of a target picture of a landscape (T2), following the face at different time intervals. Results showed no attentional blink effect (i.e., no deterioration in T2 accuracy) when T1 was an angry face with direct gaze, whereas it was present for angry faces with averted gaze or neutral faces with either averted or direct gaze. These findings are consistent with appraisal theories and are discussed against the background of automatic processing of threat stimuli.

Two experiments, one on school-aged children and one on adults, explored the mechanisms underlying responses to an image prime (hand vs. control object) followed by graspable objects that were, in certain cases, dangerous. Participants were presented with different primes (a male, a female and a robotic grasping-hand; a male and a female static-hand; a control stimulus) and objects representing two risk levels (neutral and dangerous). The task required that a natural/artifact categorization task be performed by pressing different keys. In both adults and children graspable objects activated a facilitating motor response, while dangerous objects evoked aversive affordances, generating an interference-effect. Both children and adults were sensitive to the distinction between biological and non-biological hands, however detailed resonant mechanisms related to the hand-prime gender emerged only in adults. Implications for how the concept of “dangerous object” develops and the relationship between resonant mechanisms and perception of danger are discussed.

Facial emotions and emotional body postures can easily grab attention in social communication. In the context of faces, gaze has been shown as an important cue for orienting attention, but less is known for other important body parts such as hands. In the present study we investigated whether hands may orient attention due to the emotional features they convey. By implying motion in static photographs of hands, we aimed at furnishing observers with information about the intention to act and at testing if this interacted with the hand automatic coding. In this study, we compared neutral and frontal hands to emotionally threatening hands, rotated along their radial-ulnar axes in a Sidedness task (a Simon-like task based on automatic access to body representation). Results showed a Sidedness effect for both the palm and the back views with either neutral and emotional hands. More important, no difference was found between the two views for neutral hands, but it emerged in the case of the emotional hands: faster reaction times were found for the palm than the back view. The difference was ascribed to palm views' "offensive" pose: a source of threat that might have raised participants' arousal. This hypothesis was also supported by conscious evaluations of the dimensions of valence (pleasant-unpleasant) and arousal. Results are discussed in light of emotional feature coding.

Purpose PEFG regimen (P:cisplatin, E:epirubicin, F:5-fluorouracil, G:gemcitabine) significantly prolonged progression-free (PFS) and overall survival (OS) of patients with advanced pancreatic adenocarcinoma (PA) with respect to standard gemcitabine. The current trial was aimed at assessing whether the replacement of E with docetaxel (D) may improve 6 months PFS (PFS6). Methods Chemo-naive patients with stage III or metastatic PA received P (30 mg/m(2) day 1 and 15), G (800 mg/m(2) day 1 and 15), and capecitabine (1,250 mg/m(2)/day days 1-28, without a break) and were randomized to receive either D at 25-30 mg/m(2) day 1 and 15 (arm A: PDXG regimen) or E at 30 mg/m(2) day 1 and 15 (arm B: PEXG regimen). Cycles were repeated every 28 days for a maximum of 6 months. The Fleming design was used to calculate the sample size on the probability of being PFS6. Assuming P0 = 40% and P1 = 60%, alpha = 0.05 and beta = 0.10; the study was to enroll 52 patients per arm. Results Between July 2005 and September 2008, 105 patients were enrolled, stratified by stage and randomized. Patients' characteristics were (A/B) the following: median age 61/59, PS > 70 92/88%, metastatic disease 66/65%. PFS6 was 58%, and median OS was 11 months in both arms. A partial response was observed in 60/37% of patients. Main per cycle G3-4 toxicity was the following: neutropenia 4/13%, thrombocytopenia 2/4%, anemia 4/4%, and fatigue 6/3%. Conclusions The inclusion of D instead of E yielded more objective response and less G3-4 neutropenia but did not improve PFS and OS. The present trial confirms the relevant impact on outcome of advanced PA of 4-drug regimens. PURPOSE: PEFG regimen (P:cisplatin, E:epirubicin, F:5-fluorouracil, G:gemcitabine) significantly prolonged progression-free (PFS) and overall survival (OS) of patients with advanced pancreatic adenocarcinoma (PA) with respect to standard gemcitabine. The current trial was aimed at assessing whether the replacement of E with docetaxel (D) may improve 6 months PFS (PFS6). METHODS: Chemo-naive patients with stage III or metastatic PA received P (30 mg/m(2) day 1 and 15), G (800 mg/m(2) day 1 and 15), and capecitabine (1,250 mg/m(2)/day days 1-28, without a break) and were randomized to receive either D at 25-30 mg/m(2) day 1 and 15 (arm A: PDXG regimen) or E at 30 mg/m(2) day 1 and 15 (arm B: PEXG regimen). Cycles were repeated every 28 days for a maximum of 6 months. The Fleming design was used to calculate the sample size on the probability of being PFS6. Assuming P0 = 40% and P1 = 60%, α = 0.05 and β = 0.10; the study was to enroll 52 patients per arm. RESULTS: Between July 2005 and September 2008, 105 patients were enrolled, stratified by stage and randomized. Patients' characteristics were (A/B) the following: median age 61/59, PS >70 92/88%, metastatic disease 66/65%. PFS6 was 58%, and median OS was 11 months in both arms. A partial response was observed in 60/37% of patients. Main per cycle G3-4 toxicity was the following: neutropenia 4/13%, thrombocytopenia 2/4%, anemia 4/4%, and fatigue 6/3%. CONCLUSIONS: The inclusion of D instead of E yielded more objective response and less G3-4 neutropenia but did not improve PFS and OS. The present trial confirms the relevant impact on outcome of advanced PA of 4-drug regimens.

BACKGROUND: Biliary tract adenocarcinoma (BTA) is an uncommon tumor with a poor prognosis and no standard, systemic chemotherapy. The combined cisplatin, epirubicin, 5-fluorouracil, and gemcitabine (PEFG) regimen is an effective, upfront treatment for advanced pancreatic cancer. In this study, the authors assessed the activity and safety of this combination regimen in patients with advanced BTA. METHODS: PEFG (cisplatin 40 mg/m2 and epirubicin 40 mg/m2 on Day 1; gemcitabine 600 mg/m2 on Days 1 and 8; and 5-fluorouracil [FU] 200 mg/m2 daily as a continuous infusion) was administered to chemotherapy-naive patients who had a cytologic or histologic diagnosis of locally advanced or metastatic BTA, aged ≤75 years, and a performance status (PS) >60 either until they had evidence progressive disease or for a maximum of 6 months. Tumor size was assessed every 2 months during treatment. RESULTS: Between May 1999 and December 2005, 37 patients (62% metastatic) who had a median age of 62 years and a median PS of 90 received the PEFG regimen at the authors' institution. Primary tumor sites were the intrahepatic bile duct in 10 patients (27%), the extrahepatic bile duct in 8 patients (22%), the gallbladder in 12 patients (32%), and the ampulla of Vater in 7 patients (19%). A partial response was observed in 16 patients (43%), and stable disease was observed in 12 patients (32%). The median overall survival (OS) was 12.1 months, and the 1-year OS rate was 52%. The median progression-free survival (PFS) was 7.9 months, and the 6-month PFS rate was 67%. The main grade 3/4 toxicity was neutropenia in 18% of cycles followed by thrombocytopenia in 9% of cycles, nausea/vomiting in 5% of cycles, and febrile neutropenia, fatigue, anemia, and stomatitis in 2% of cycles. CONCLUSIONS: The current results demonstrated that PEFG was an active regimen with a manageable toxicity profile for patients with advanced BTA. Cancer 2010. © 2010 American Cancer Society.

In the present study two separate stimulus–response compatibility effects (functional affordance and Simon-like effects) were investigated with centrally presented pictures of an object tool (a torch) characterized by a structural separation between the graspable portion and the goal-directed portion. In Experiment 1, participants were required to decide whether the torch was red or blue, while in Experiment 2 they were required to decide whether the torch was upright or inverted. Our results showed that with the same stimulus two types of compatibility effect emerged: one based on the direction signalled by the goal-directed portion of the tool (a Simon-like effect as observed in Experiment 1), and the other based on the actions associated with an object (a functional affordance effect as observed in Experiment 2). Both effects emerged independently of the person's intention to act on the stimulus, but depended on the stimulus properties that were processed in order to perform the task.

We carried out three experiments aimed at testing whether hand posture affects the compatibility effect that Chen and Bargh (1999) found between a word’s emotional connotation and arm movement direction. In the present study, participants responded by pressing two buttons: one placed near their body, the other far away. In Experiment 1, in which they pressed the response button with their hand open, RTs were shorter when participants pressed the far button for positive words and the near button for negative words, as if they simulated reaching for something good and avoiding something bad. However, in Experiments 2 and 3, in which participants pressed the response button with a tennis ball in their hand, RTs were shorter when participants pressed the near button for positive words and the far button for negative words, as if they simulated drawing a good thing closer and pushing a bad thing away. Results are discussed within the framework of theories on concept grounding in emotion and action systems.

Background PEFG regimen (cisplatin and epirubicin 40 mg/m(2) day 1, gemcitabine 600 mg/m(2) days 1 and 8, 5-fluorouracil (FU) 200 mg/m(2)/day continuous infusion) significantly improved the outcome of patients with advanced pancreatic adenocarcinoma (PA) with respect to standard gemcitabine in a previous phase III trial. This regimen was subsequently modified in a dose-finding study by increasing dose intensity of cisplatin and epirubicin (both at 30 mg/m(2) every 14 days) and of gemcitabine (at 800 mg/m(2) every 14 days). Results of a consecutive series treated by dose-intense PEFG regimen are herewith reported. Material and methods Dose-intense PEFG was administered to chemotherapy-naive patients with stages III-IV PA, < 75 years, performance status (PS) > 50, till progressive disease or for a maximum of 6 months. Results Between January 2004 and June 2005, 49 (31 or 63% metastatic) patients, median age 62 years, median PS 80, were treated with dose-intense PEFG. Partial response and stable disease was observed in 24 (49%) and 16 (33%) patients, respectively; 31 patients were progression-free at 6 months (PFS-6 = 63%). Median survival was 10.5 months and 1-year overall survival (OS) was 48% (95% confidence interval: 33-61%). Main grade 3-4 toxicity was: neutropenia in 26% of patients, stomatitis and fatigue in 8%, anaemia, diarrhoea, nausea/vomit in 6%, febrile neutropenia and thrombocytopaenia in 4%, hand-foot syndrome in 2%. Conclusion When compared with 84 patients treated by classical PEFG at the same institution, dose-intense PEFG was not inferior in terms of PFS-6 (63 versus 57%), 1-year OS (48 versus 42%) and response rate (49 versus 49%); it allowed to increase dose intensity for gemcitabine by 32%, for cisplatin and epirubicin by 36% (FU reduced by 3%), to significantly reduce grade 3-4 hematological toxicity (neutropenia: 26 versus 86%; P < 0.00001; thrombocytopaenia: 4 versus 58%; P < 0.00001) and to reduce by one-third the number of outpatient accesses. The new PEFG schedule appears more suitable for clinical use and should be preferred as a basis for further development of therapeutic strategies against pancreatic cancer.

Summary Background Patients with advanced pancreatic adenocarcinoma have a poor response, progression-free survival, and overall survival with standard treatment. We aimed to assess whether a four-drug regimen could improve 4 month progression-free survival compared with gemcitabine alone. Methods In a randomised multicentre phase III trial, 52 patients were randomly assigned to 40 mg/m 2 cisplatin and 40 mg/m 2 epirubicin both given on day 1, 600 mg/m 2 gemcitabine given intravenously over 1 h on days 1 and 8, and 200 mg/m 2 fluorouracil a day given by continuous infusion on days 1–28 of a 4-week cycle (PEFG regimen), and 47 were assigned to 1000 mg/m 2 gemcitabine given intravenously over 30 min once a week for 7 of 8 consecutive weeks in cycle 1 and for 3 of 4 weeks thereafter. The primary endpoint was 4-month progression-free survival. Secondary endpoints were overall survival, objective response, safety, and quality of life. Analyses were by intention to treat. Findings 51 patients assigned PEFG and 46 assigned gemcitabine alone had disease progression. 49 patients in the PEFG group and 46 in the gemcitabine group died from progressive disease. More patients allocated PEFG than gemcitabine alone were alive without progressive disease at 4 months (60% [95% CI 46–72] vs 28% [17–42]; hazard ratio [HR] 0·46 [0·26–0·79]). 1-year overall survival in the PEFG group was 38·5% (25·3–51·7) and in the gemcitabine group was 21·3% (9·6–33·0; HR 0·68 [0·42–1·09]). More patients assigned PEFG showed disease response than did those assigned gemcitabine (38·5% [25·3–51·7] vs 8·5% [0·5–16·5]; odds ratio 6·60 [2·11–20·60], p=0·0008). More patients in the PEFG group had grade 3–4 neutropenia and thrombocytopenia than in the gemcitabine group (p Interpretation The PEFG regimen could be considered for treatment of advanced pancreatic adenocarcinoma.

Background: This study evaluates the maximum tolerated dose (MTD) and activity of mitomycin, docetaxel. and irinotecan (MDI) regimen on metastatic pancreatic adenocarcinoma, previously treated with gemcitabine-containing chemotherapy. Patients and Methods: Patients with less than 76 years, Karnofsky performance status greater than or equal to60, and adequate bone marrow, kidney, and liver function were eligible for this trial. Treatment consisted of mitomycin 6 mg/m(2) day 1, docetaxel and irinotecan on days 2 and 8 with escalating doses, every 4 weeks. Dose levels were level 1:30 and 70 mg/m2; level 2:30 and 100 mg/m(2) level 3:30 and 85 mg/m(2); and level 4:35 and 85 mg/m(2) Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia >7 days, febrile neutropenia, grade 4 thrombocytopenia, nausea and vomiting, or diarrhea, grade greater than or equal to3 nonhematological toxicity, or failure to recover to grade less than or equal to1 toxicity by day 43, occurring during the first cycle of chemotherapy. Results: Between September 2001 and October 2002, 15 eligible patients, three of whom had been previously treated with two lines of chemotherapy, received 33 cycles of MDI. Toxicity consisted of grade 3 to 4 neutropenia in 23% of cycles, fatigue, diarrhea, and vomiting in 10% of cycles, and one toxic death. DLT was observed in 2 of 6 level 2 patients (one toxic death and one grade 3 fatigue), and 2 of 3 level 4 patients (one neutropenic fever and one grade 3 fatigue). Thirteen patients were assessable for response. No objective response was observed among patients treated with MTD or higher doses. Three patients had stable disease; all other patients had progressive disease. The median time to tumor progression and median Survival was 1.7 and 6.1 months, respectively. Conclusion: The MTD was mitomycin 6 mg/m(2) day one, and docetaxel 30 and irinotecan 85 mg/m(2) days 2 and 8. This regimen is inactive in metastatic pancreatic cancer.

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Objectives: In patients with non-small cell lung cancer (NSCLC) the presence of satellite metastatic nodules may he considered a contraindication to surgical treatment. The use of spiral computed tomography (CT) scan has improved the accuracy of the diagnostic assessment of pulmonary diseases. but has also led to the detection of a consistent number of indeterminate satellite lesions. Obtaining a differential diagnosis of these lesions is extremely important in defining the therapeutic strategy. The aim of the study was, to assess the characteristics of satellite nodules in patients with NSCLC and to examine the diagnostic and therapeutic approach used in the presence of indeterminate satellite lesions. Methods: From November 1995 to February, 2001, 29 patients (mean age 64 years) who underwent surgery for NSCLC had indeterminate satellite pulmonary lesions at the preoperative spiral CT scan A differential diagnosis of the nodules was obtained by histological examination in 27 patients and by follow-up (62 and 64 months respectively) in two patients. Positron emission tomography (PET) scan was selectively performed in the preoperative evaluation. Results: Thirty-two satellite nodules were analyzed in the group of 29 patients. The size of the lesions varied from 2 to 15 mm (mean 8 mm). The nodules were ipsilateral to the primary tumor in 25 patients and contralateral in four. They were benign in 22 cases and malignant in ten (metastases from NSCLC in seven patients and second primary lung cancer in three). Nodules with a size equal to or less than 5 mm were more frequently benign. Patients with stage III tumors had a higher incidence of malignant satellite nodules in comparison to earlier stages. although the data did not reach statistical significance, PET scat, correctly differentiated benign and malignant satellite nodules in six patients. Conclusions: Obtaining a differential diagnosis of indeterminate pulmonary nodules associated to NSCLC is of great importance in defining the therapeutic strategy. The results of this study show that indeterminate satellite lesions may be benign or represent a second primary lung cancer, and should not therefore be considered a contraindication to surgical exploration when a preliminary differential diagnosis by other means cannot he obtained. (C) 2002 Elsevier Science B.V. All rights reserved. RI ciriaco, paola/H-5716-2012

PURPOSE: To evaluate the efficacy and toxicity of a cisplatin, epirubicin, gemcitabine, and fluorouracil (PEF-G) schedule on stage IV pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients ≤ 70 years, with no prior chemotherapy and with bidimensionally measurable stage IV pancreatic adenocarcinoma, Eastern Cooperative Oncology Group performance status ≤ 2, and adequate bone marrow, kidney, and liver function were eligible for this trial. Eligibility criteria for clinical benefit assessment were pain with at least a daily analgesic consumption of two nonsteroidal anti-inflammatory drugs or Karnofsky performance status between 50 and 70. Treatment consisted of 40 mg/m2 each of cisplatin and epirubicin day 1, gemcitabine 600 mg/m2 on days 1 and 8 every 4 weeks, and fluorouracil 200 mg/m2/d as a protracted venous infusion. RESULTS: Between April 1997 and April 1999, 49 patients from a single institution were eligible for the study. Altogether, 203 cycles (median, four cycles) of PEF-G were delivered. The objective response rate was 58% in 43 assessable patients and 51% in the intent-to-treat population. Fourteen patients had stable disease. Grade 3 or 4 World Health Organization neutropenia occurred in 51% of cycles, thrombocytopenia in 28%, anemia in 7%, stomatitis in 5%, and diarrhea, and nausea, and vomiting in 2%. The median duration of response was 8.5 months. The median time to tumor progression was 7.5 months. The median survival was 11 months in the assessable population and 10 months in the intent-to-treat population. Clinical benefit was achieved in 22 (78%) of 28 assessable patients. CONCLUSION: PEF-G is a well-tolerated and safe regimen; it obtained a very high rate of durable responses and deserves further evaluation in a phase III trial.

It has been demonstrated that visual objects activate responses spatially corresponding to the orientation (left or right) of their graspable parts. To investigate the role of attention orienting in the generation of this effect, which we will refer to as affordance effect, we ran three experiments in which the target stimulus could either correspond or not with a dynamic event capturing attention. Participants were required to press a left or right key according to the vertical orientation (upward or inverted) of objects presented with their handles oriented to the right or to the left. In Experiments 1 and 2, the objects were located above or below fixation, while in Experiment 3, to assess the contemporary presence of the affordance and Simon effects, the objects were located to the left or right of fixation. The results showed that while the affordance effect, when evident, was always relative to the target object, irrespective of its attentional capturing properties, the Simon effect occurred relative to the event capturing attention. These findings suggest that automatic and controlled processes of visual attention may play a differential role in the occurrence of the two effects.