Role of Reflux in the Pathogenesis of Eosinophilic Esophagitis: Comprehensive Appraisal With Off- and On PPI Impedance-pH Monitoring.

OBJECTIVES: Role of reflux and mechanisms of response to proton pump inhibitor (PPI) therapy in eosinophilic esophagitis (EoE) have not yet been fully elucidated. Comprehensive assessment by impedance-pH monitoring could clarify these issues. METHODS: Prospective multicenter study comparing EoE patients with healthy controls and gastroesophageal reflux disease cases. Patients with EoE were evaluated off- and on PPI; responsiveness was assessed by histology. Impedance-pH appraisal included chemical clearance, assessed with the postreflux swallow-induced peristaltic wave (PSPW) index, and mucosal integrity measured with mean nocturnal baseline impedance (MNBI). RESULTS: Sixty consecutive patients with EoE were compared with 60 age- and sex-matched healthy controls and 60 subjects with gastroesophageal reflux disease. The number of total refluxes was higher, while the PSPW index was lower in patients with EoE than in healthy controls. Off PPI, a lower MNBI gradient between the mid and distal esophagus distinguished 20 patients with PPI-refractory EoE from 40 patients with PPI-responsive EoE and was a predictor of PPI failure. On PPI, a lower PSPW index was the sole reflux parameter distinguishing PPI-refractory from PPI-responsive EoE; all reflux parameters improved in PPI-responsive patients, whereas the PSPW index was not modified in PPI-refractory cases and was independently associated with PPI-responsiveness. MNBI in the distal and mid esophagus improved much more in PPI-responsive than in PPI-refractory EoE. DISCUSSION: Reflux plays a role in the pathogenesis of EoE, more relevant in PPI-responsive cases. Low impedance gradient between the mid and distal esophagus may be useful to predict PPI refractoriness. PPIs mainly act by improving chemical clearance, i.e., by an antireflux action supporting long-term prescription in PPI-responsive EoE.

Liver Angiopoietin-2 Is a Key Predictor of De Novo or Recurrent Hepatocellular Cancer After Hepatitis C Virus Direct-Acting Antivirals.

Recent reports suggested that direct acting antivirals (DAAs) might favor hepatocellular carcinoma (HCC). In study 1, we studied the proangiogenic liver microenvironment in 242 DAA-treated chronic hepatitis C patients with advanced fibrosis. Angiopoietin-2 (ANGPT2) expression was studied in tissue (cirrhotic and/or neoplastic) from recurrent, de novo, nonrecurrent HCC, or patients never developing HCC. Circulating ANGPT2,vascular endothelial growth factor (VEGF), and C-reactive protein (CRP) were also measured. In study 2, we searched for factors associated with de novo HCC in 257 patients with cirrhosis of different etiologies enrolled in a dedicated prospective study. Thorough biochemical, clinical, hemodynamic, endoscopic, elastographic, and echo-Doppler work-up was performed in both studies. In study 1, no patients without cirrhosis developed HCC. Of 183 patients with cirrhosis, 14 of 28 (50.0%) with previous HCC recurred whereas 21 of 155 (13.5%) developed de novo HCC. Patients with recurrent and de novo HCCs had significantly higher liver fibrosis (LF) scores, portal pressure, and systemic inflammation than nonrecurrent HCC or patients never developing HCC. In recurrent/de novo HCC patients, tumor and nontumor ANGPT2 showed an inverse relationship with portal vein velocity (PVv; r = -0.412, P = 0.037 and r = -0.409, P = 0.047 respectively) and a positive relationship with liver stiffness (r = 0.526, P = 0.007; r = 0.525, P = 0.003 respectively). Baseline circulating VEGF and cirrhotic liver ANGPT2 were significantly related (r = 0.414, P = 0.044). VEGF increased during DAAs, remaining stably elevated at 3-month follow-up, when it significantly related with serum ANGPT2 (r = 0.531, P = 0.005). ANGPT2 expression in the primary tumor or in cirrhotic tissue before DAAs was independently related with risk of HCC recurrence (odds ratio [OR], 1.137; 95% confidence interval [CI], 1.044-1.137; P = 0.003) or occurrence (OR, 1.604; 95% CI, 1.080-2.382; P = 0.019). In study 2, DAA treatment (OR, 4.770; 95% CI, 1.395-16.316; P = 0.013) and large varices (OR, 3.857; 95% CI, 1.127-13.203; P = 0.032) were independent predictors of de novo HCC. CONCLUSION: Our study indicates that DAA-mediated increase of VEGF favors HCC recurrence/occurrence in susceptible patients, that is, those with more severe fibrosis and splanchnic collateralization, who already have abnormal activation in liver tissues of neo-angiogenetic pathways, as shown by increased ANGPT2. (Hepatology 2018; 00:000-000).

Computed tomography or contrast-enhanced ultrasonography for follow-up of liver metastases after Cyberknife therapy?: A prospective pilot study.

OBJECTIVES: Contrast-enhanced ultrasonography (CEUS) allows the study of vascularization of secondary liver lesions. The Cyberknife (Accuray, Inc, Sunnyvale, CA) is a therapeutic method that allows a tumor target to be subjected to a high radiant dose gradient. This prospective pilot study aimed to demonstrate the concordance of CEUS versus contrast-enhanced computed tomography (CECT) in determining the stability or disease progression of secondary liver lesions after treatment with the Cyberknife. METHODS: Twenty-four patients were consecutively enrolled, and 3 different operators evaluated the CEUS images and the intermodality concordance with CECT. All patients received CEUS at 1 and 2 months after the Cyberknife therapy. The intermodality agreement was evaluated by the Cohen κ coefficient and a multivariate analysis according to the method of Janson and Olsson (Educ Psychol Meas 2001; 61:277-289). RESULTS: Forty secondary liver lesions were detected and treated. Forty-one CECT and 51 CEUS examinations were performed without any adverse events in the 24 patients. The intermodality agreement rates, calculated for the operators as Cohen κ values, were κ = 1.00, 0.881, and 0.767, respectively. The multivariate analysis of intermodality agreement showed an almost perfect value (ι = 0.841). CONCLUSIONS: This pilot study found excellent diagnostic correspondence between CEUS and CECT in the evaluation of local disease stability or progression after Cyberknife therapy in liver metastases. These findings suggest that CEUS could play an important role in the surveillance of these patients because of its high accuracy and reproducibility, thus reducing the need for CECT.

Lack of response to conspecific juvenile vocalizations in two avian brood parasites.

Juveniles of interspecific avian brood parasites need to locate and recognize conspecifics to continue their life cycle after being reared by individuals of another species. However, little is known about the recognition mechanisms and cues involved in this critical stage of their lives. It has been proposed that adult parasites could show some kind of parental behavior by actively searching and interacting with conspecific young, which in turn could serve the juveniles to learn and/or reinforce the learning of conspecific characteristics. Since acoustic communication is one of the main channels used by birds, if such form of parental behavior by adult avian brood parasites does exist, adult cowbirds should recognize and respond positively to vocalizations of conspecific juveniles. We experimentally tested whether adult shiny Molothrus bonariensis and screaming M. rufoaxillaris cowbirds respond positively towards acoustic signals of conspecific juveniles using two playback experiments, one conducted in semi-captivity and the other in the field. In both cases, we presented 3 types of playbacks to adults of both cowbird species: vocalizations of shiny cowbird juveniles, vocalizations of screaming cowbird juveniles, and white noise as a control. In the experiment in semi-captivity, no significant differences were found between treatments. In the field experiment, no conspecifics approached the playback area, but hosts of the species whose playback was played were attracted to the loudspeaker. In conclusion, our results do not support the predictions we tested from the parental behavior hypothesis and indicate that adult shiny and screaming cowbirds do not respond positively to acoustic signals of conspecific juveniles, at least not to the type of signals used in our experiments.

A novel method of rejection of brood parasitic eggs reduces parasitism intensity in a cowbird host.

The hosts of brood parasitic birds are under strong selection pressure to recognize and remove foreign eggs from their nests, but parasite eggs may be too large to be grasped whole and too strong to be readily pierced by the host's bill. Such operating constraints on egg removal are proposed to force some hosts to accept parasite eggs, as the costs of deserting parasitized clutches can outweigh the cost of rearing parasites. By fitting microcameras inside nests, we reveal that the Neotropical baywing (Agelaioides badius), a host of the screaming cowbird (Molothrus rufoaxillaris) and shiny cowbird (Molothrus bonariensis), instead circumvents such constraints by kicking parasite eggs out of the nest. To our knowledge, this is the first report of a passerine bird using its feet to remove objects from the nest. Kick-ejection was an all-or-nothing response. Baywings kick-ejected parasite eggs laid before their own first egg and, if heavily parasitized, they ejected entire clutches and began again in the same nest. Few baywings were able to rid their nests of every parasite egg, but their novel ejection method allowed them to reduce the median parasitism intensity by 75 per cent (from four to one cowbird eggs per nest), providing an effective anti-parasite defence.

Host-parasite coevolution beyond the nestling stage? Mimicry of host fledglings by the specialist screaming cowbird.

Egg mimicry by obligate avian brood parasites and host rejection of non-mimetic eggs are well-known textbook examples of host-parasite coevolution. By contrast, reciprocal adaptations and counteradaptations beyond the egg stage in brood parasites and their hosts have received less attention. The screaming cowbird (Molothrus rufoaxillaris) is a specialist obligate brood parasite whose fledglings look identical to those of its primary host, the baywing (Agelaioides badius). Such a resemblance has been proposed as an adaptation in response to host discrimination against odd-looking young, but evidence supporting this idea is scarce. Here, we examined this hypothesis by comparing the survival rates of young screaming cowbirds and non-mimetic shiny cowbirds (Molothrus bonariensis) cross-fostered to baywing nests and quantifying the similarity in plumage colour and begging calls between host and cowbird fledglings. Shiny cowbirds suffered higher post-fledging mortality rates (83%) than screaming cowbirds (0%) owing to host rejection. Visual modelling revealed that screaming cowbirds, but not shiny cowbirds, were indistinguishable from host young in plumage colour. Similarly, screaming cowbirds matched baywings' begging calls more closely than shiny cowbirds. Our results strongly support the occurrence of host fledgling mimicry in screaming cowbirds and suggest a role of visual and vocal cues in fledgling discrimination by baywings.

A Natural Human-Drone Embodied Interface: Empirical Comparison With a Traditional Interface.

Despite the importance of usability in human-machine interaction (HMI), most commonly used devices are not usable by all potential users. In particular, users with low or null technological experience, or with special needs, require carefully designed systems and easy-to-use interfaces supporting recognition over recall. To this purpose, Natural User Interfaces (NUIs) represent an effective strategy as the user's learning is facilitated by features of the interface that mimic the human "natural" sensorimotor embodied interactions with the environment. This paper compares the usability of a new NUI (based on an eye-tracker and hand gesture recognition) with a traditional interface (keyboard) for the distal control of a simulated drone flying in a virtual environment. The whole interface relies on "dAIsy", a new software allowing the flexible use of different input devices and the control of different robotic platforms. The 59 users involved in the study were required to complete two tasks with each interface, while their performance was recorded: (a) exploration: detecting trees embedded in an urban environment; (b) accuracy: guiding the drone as accurately and fast as possible along a predefined track. Then they were administered questionnaires regarding the user's background, the perceived embodiment of the device, and the perceived quality of the virtual experience while either using the NUI or the traditional interface. The results appear controversial and call for further investigation: (a) contrary to our hypothesis, the specific NUI used led to lower performance than the traditional interface; (b) however, the NUI was evaluated as more natural and embodied. The final part of the paper discusses the possible causes underlying these results that suggest possible future improvements of the NUI.

Differential reproductive success favours strong host preference in a highly specialized brood parasite.

Obligate avian brood parasites show dramatic variation in the degree to which they are host specialists or host generalists. The screaming cowbird Molothrus rufoaxillaris is one of the most specialized brood parasites, using a single host, the bay-winged cowbird (Agelaioides badius) over most of its range. Coevolutionary theory predicts increasing host specificity the longer the parasite interacts with a particular avian community, as hosts evolve defences that the parasite cannot counteract. According to this view, host specificity can be maintained if screaming cowbirds avoid parasitizing potentially suitable hosts that have developed effective defences against parasitic females or eggs. Specialization may also be favoured, even in the absence of host defences, if the parasite's reproductive success in alternative hosts is lower than that in the main host. We experimentally tested these hypotheses using as alternative hosts two suitable but unparasitized species: house wrens (Troglodytes aedon) and chalk-browed mockingbirds (Mimus saturninus). We assessed host defences against parasitic females and eggs, and reproductive success of the parasite in current and alternative hosts. Alternative hosts did not discriminate against screaming cowbird females or eggs. Egg survival and hatching success were similarly high in current and alternative hosts, but the survival of parasitic chicks was significantly lower in alternative hosts. Our results indicate that screaming cowbirds have the potential to colonize novel hosts, but higher reproductive success in the current host may favour host fidelity.

Metabolomic analysis with 1H-NMR for non-invasive diagnosis of hepatic fibrosis degree in patients with chronic hepatitis C.

BACKGROUND: The assessment of fibrosis degree in liver diseases is based on several non-invasive techniques, but none has been accurate. AIM: This study employed proton nuclear magnetic resonance spectroscopy to identify metabolic profiles in serum and urine, specific for different fibrosis degree in chronic hepatitis C patients. METHOD: 71 plasma, 73 serum, and 578 urine samples were collected. All samples were analyzed using 1H-NMR spectroscopy technique and three different NMR spectra were acquired for each serum/plasma sample. The data analyses were performed by partial least square regression, principal component analysis, and Monte Carlo cross-validation in a supervised methodology. RESULTS: The cross-validation test correctly assigned each sample to its specific donor with 98.44% accuracy for urine samples and 65% for serum/plasma samples. Advanced fibrosis and cirrhosis were recognized with 71% sensitivity for CPMG plasma spectra and 69% specificity for NOESY serum spectra. Accuracy for NOESY serum spectra was 68%. Noesy spectra recognized advanced fibrosis and cirrhosis with 71% sensitivity, 30% specificity, and 50% accuracy in urine samples. CONCLUSION: Metabolomic analysis of urine spectra using 1H-NMR spectroscopy can recognize a specific individual profile in all patients with chronic hepatitis C. However, this method cannot yet differentiate with sufficient accuracy, patients with advanced fibrosis from patients with milder disease.

Percutaneous ultrasound-guided fiducial marker placement for liver cancer robotic stereotactic radio-surgery treatment: A comparative analysis of three types of markers and needles.

BACKGROUND AND STUDY AIMS: Percutaneous placement of fiducial markers is required to perform stereotactic body radiation therapy (SBRT) for liver neoplastic lesions. This prospective trial was designed to evaluate the feasibility and safety of percutaneous ultrasound-guided placement of three different types of markers in patients with liver cancer referred for SBRT. PATIENTS AND METHODS: Fifty patients underwent percutaneous ultrasound-guided implantation of a fiducial marker in the liver. Three sizes of needles were used: 25 gauge (G), 22G, and 17G. The 25G and 22G needles contained gold anchor markers of 0.28×10mm and 0.4 ×10mm size, respectively. In contrast, the 17G needle contained a gold grain marker of 1×4mm. Each patient received 1-6 markers, depending on lesion size and numbers. Technical feasibility and the occurrence of adverse events were registered. Computed tomography scans were acquired prior to SBRT to evaluate the location, visibility, or complications related to the markers. RESULTS: A total of 163 needles were used to deliver 163 markers in 50 patients. No major complications occurred. Minor complication occurrence rate was 12%. The total complication occurrence for all type of markers was 8.5%. No complications were observed with the use of the gold anchor marker of 0.4 ×10mm size. Variance analysis of the three markers showed a significant difference in the frequency of complications amongst the three markers (p<0.01). CONCLUSION: Percutaneous ultrasound-guided placement of fiducial markers for SBRT of liver neoplastic lesions is safe and feasible. In our series, the 22G needle showed some advantage in terms of handling and safety when compared with the 25G and 17G needles. In addition, the gold anchor marker of 0.4 ×10mm size displayed a lower percentage of displacement.

Factors Predictive of Improved Abdominal Ultrasound Visualization after Oral Administration of Simethicone.

Ultrasonography is a non-invasive, accurate and low-cost technique used to study the upper abdomen, but it has reduced reliability in the study of the pancreas and retroperitoneum. Simethicone is a well-known emulsifying agent that has been used to improve ultrasonographic visualization. The aim of this study was to identify anthropometric parameters that are able to predict a good response to simethicone in improving ultrasonographic visualization of abdominal structures. One hundred twenty-seven patients were recruited. After basal examination, their anthropometric parameters were collected. Patients with an incomplete upper abdominal examination because of gastrointestinal gas have greater body mass index, waist circumference and abdominal wall thickness. In our study, the best anthropometric parameter for identifying patients with poor visualization at abdominal ultrasound examination is waist circumference. Using a cutoff of 84 cm, we can identify patients with poor visibility at abdominal ultrasound examination (group B) with a sensitivity of 90%.

Therapeutic usability of two different fiducial gold markers for robotic stereotactic radiosurgery of liver malignancies: A pilot study.

AIM: To assess how the application of different types of markers affects the tracking accuracy of CyberKnife's. METHODS: Fifteen patients were recruited and subjected to the ultrasound-guided placement of markers. Two different type of needles 25 gauge (G) and 17 G containing two different fiducial marker, gold notched flexible anchor wire 0.28 mm × 10 mm (25 G needle) and gold cylindrical grain 1 mm × 4 mm (17 G), were used. Seven days after the procedure, a CyberKnife planning computed tomography (CT) for the simulation of radiation treatment was performed on all patients. A binary CT score was assigned to the fiducial markers visualization. Also, the CT number was calculated for each fiducial and the values compared with a specific threshold. RESULTS: For each patient from 1 to 5, intra-hepatic markers were placed (one in 2 patients, three in 8 patients, four in 3 patients, and five in 2 patients). A total of 48 needles were used (thirty-two 17 G and sixteen 25 G) and 48 gold markers were placed (32 Grain shaped markers and 16 Gold Anchor). The result showed that the CT visualization of the grain markers was better than the anchor markers (P = 5 × 10(-9)). Furthermore, the grain markers were shown to present minor late complications (P = 3 × 10(-6)), and the best CT threshold number (P = 0.0005). CONCLUSION: The study revealed that the Gold Anchor fiducial marker is correlated with a greater number of late minor complications and low visualization by the CT.

Intrinsic motivations drive learning of eye movements: an experiment with human adults.

Intrinsic motivations drive the acquisition of knowledge and skills on the basis of novel or surprising stimuli or the pleasure to learn new skills. In so doing, they are different from extrinsic motivations that are mainly linked to drives that promote survival and reproduction. Intrinsic motivations have been implicitly exploited in several psychological experiments but, due to the lack of proper paradigms, they are rarely a direct subject of investigation. This article investigates how different intrinsic motivation mechanisms can support the learning of visual skills, such as "foveate a particular object in space", using a gaze contingency paradigm. In the experiment participants could freely foveate objects shown in a computer screen. Foveating each of two "button" pictures caused different effects: one caused the appearance of a simple image (blue rectangle) in unexpected positions, while the other evoked the appearance of an always-novel picture (objects or animals). The experiment studied how two possible intrinsic motivation mechanisms might guide learning to foveate one or the other button picture. One mechanism is based on the sudden, surprising appearance of a familiar image at unpredicted locations, and a second one is based on the content novelty of the images. The results show the comparative effectiveness of the mechanism based on image novelty, whereas they do not support the operation of the mechanism based on the surprising location of the image appearance. Interestingly, these results were also obtained with participants that, according to a post experiment questionnaire, had not understood the functions of the different buttons suggesting that novelty-based intrinsic motivation mechanisms might operate even at an unconscious level.

Visual interaction: models, systems, prototypes. The Pictorial Computing Laboratory at the University of Rome La Sapienza.

This paper reports on the research activities performed by the Pictorial Computing Laboratory at the University of Rome, La Sapienza, during the last 5 years. Such work, essentially is based on the study of humancomputer interaction, spans from metamodels of interaction down to prototypes of interactive systems for both synchronous multimedia communication and groupwork, annotation systems for web pages, also encompassing theoretical and practical issues of visual languages and environments also including pattern recognition algorithms. Some applications are also considered like e-learning and collaborative work.