Marta Gil

A distance-based statistical analysis of fuzzy number-valued data

Abstract Real-life data associated with experimental outcomes are not always real-valued. In particular, opinions, perceptions, ratings, etc., are often assumed to be vague in nature, especially when they come from human valuations. Fuzzy numbers have extensively been considered to provide us with a convenient tool to express these vague data. In analyzing fuzzy data from a statistical perspective one finds two key obstacles, namely, the nonlinearity associated with the usual arithmetic with fuzzy data and the lack of suitable models and limit results for the distribution of fuzzy-valued statistics. These obstacles can be frequently bypassed by using an appropriate metric between fuzzy data, the notion of random fuzzy set and a bootstrapped central limit theorem for general space-valued random elements. This paper aims to review these ideas and a methodology for the statistical analysis of fuzzy number data which has been developed along the last years.

The role of habituation of the response to LiCl in the US-preexposure effect

In two experiments, rats received preexposure consisting of six intraperitoneal injections of lithium chloride (LiCl). This treatment reduced the magnitude of the unconditioned response (UR; suppressed consumption of a novel flavor) evoked by an additional injection (Experiment 1) or by oral consumption (Experiment 2) of LiCl. In both experiments, preexposure also attenuated the acquisition of a conditioned aversion with an LiCl injection as the unconditioned stimulus (US) but had no effect on the aversion produced when the US was oral consumption of LiCl (Experiment 2). These results are consistent with the view that the reduced ability of the preexposed US to serve as a reinforcer depends on blocking by injection-related cues and is independent of habituation of the UR recorded in the present study. Possible interpretations of this dissociation are discussed.

Choline dietary supplementation improves LiCl-induced context aversion retention in adult rats.

Previous studies have demonstrated that choline is an essential nutrient during prenatal and early postnatal developmental periods. Thus, the availability of choline during these periods produces some beneficial effects on hippocampal-dependent learning and memory in rats. However, research on the effect of adult choline supplementation on learning and memory abilities is scarce. In the present study, 3-4 month-old male Wistar rats receiving a 7-week choline-supplemented diet (4.5 fold that of a standard diet) and control rats receiving a standard diet were trained in a LiCl-induced contextual aversion task. Short and long-term context aversion retention was assessed by recording the consumption of a flavoured solution in the aversive and safe contexts over two subsequent tests. Statistical analysis showed that the supplemented group exhibited greater intake suppression in the aversive context than in the safe context when two retention tests were applied 3 and 15 days after conditioning. These results suggest that increasing dietary choline availability during adulthood may favour the retention of a context aversion.

Selective activity over a constitutively active RET-variant of the oral multikinase inhibitor dovitinib: Results of the CNIO-BR002 phase I-trial

Given our preclinical data showing synergy between dovitinib and paclitaxel in preclinical models we conducted this phase I trial aiming to define the recommended phase II‐dose (RP2D) on the basis of toxicity and pharmacodynamic criteria while searching for genetic variants that could sensitize patients to the regimen under study.

The Hall-Rodriguez Theory of Latent Inhibition: Further Assessment of Compound Stimulus Preexposure Effects

According to a recent theory (Hall & Rodriguez, 2010), the latent inhibition produced by nonreinforced exposure to a target stimulus (B) will be deepened by subsequent exposure of that stimulus in compound with another (AB). This effect of compound exposure is taken to depend on the addition of a novel A to the familiar B and is not predicted for equivalent preexposure on which AB trials precede the A trials. This prediction was tested in 2 experiments using rats. Experiment 1 used an aversive procedure with flavors as the stimuli; Experiment 2 used an appetitive procedure with visual and auditory stimuli. In both, we found that conditioning with B as the conditioned stimulus proceeded more slowly (i.e., latent inhibition was greater) in subjects given the B-AB sequence in preexposure than in subjects given the AB-B sequence.

A phase I trial of oncolytic adenovirus ICOVIR-5 administered intravenously to melanoma patients

Oncolytic viruses represent a unique type of agents that combine self-amplification, lytic and immunostimulatory properties against tumors. A local and locoregional clinical benefit has been demonstrated upon intratumoral injections of an oncolytic herpes virus in melanoma patients, leading to its approval in USA and Europe for patients without visceral disease (up to stage IVM1a). However, in order to debulk and change the local immunosuppressive environment of tumors that cannot be injected directly, oncolyitc viruses need to be administered systemically. Among different viruses, adenovirus has been extensively used in clinical trials but with few evidences of activity upon systemic administration. Preclinical efficacy of a single intravenous administration of our oncolytic adenovirus ICOVIR5, an adenovirus type 5 responsive to the pRB pathway commonly deregulated in tumors, led us to use this virus in a dose-escalation phase I trial in metastatic melanoma patients. The results in 12 patients, treated with a single infusion of a dose up to 1E13 viral particles, show that ICOVIR5 can reach melanoma metastases upon a single intravenous administration but fails to induce tumor regressions. These results support the systemic administration of armed oncolytic viruses to treat disseminated cancer.

A phase I trial of oncolytic adenovirus ICOVIR-5 administered intravenously to cutaneous and uveal melanoma patients

Oncolytic viruses represent a unique type of agents that combine self-amplification, lytic, and immunostimulatory properties against tumors. A local and locoregional clinical benefit has been demonstrated upon intratumoral injections of an oncolytic herpes virus in melanoma patients, leading to its approval in the United States and Europe for patients without visceral disease (up to stage IVM1a). However, in order to debulk and change the local immunosuppressive environment of tumors that cannot be injected directly, oncolyitc viruses need to be administered systemically. Among different viruses, adenovirus has been extensively used in clinical trials but with few evidences of activity upon systemic administration. Preclinical efficacy of a single intravenous administration of our oncolytic adenovirus ICOVIR5, an adenovirus type 5 responsive to the retinoblastoma pathway commonly deregulated in tumors, led us to use this virus in a dose-escalation phase 1 trial in metastatic melanoma patients. The results in 12 patients treated with a single infusion of a dose up to 1 × 1013 viral particles show that ICOVIR5 can reach melanoma metastases upon a single intravenous administration but fails to induce tumor regressions. These results support the systemic administration of armed oncolytic viruses to treat disseminated cancer.

Effect of exposure to similar flavours in sensory specific satiety: Implications for eating behaviour

Sensory-specific satiety (SSS) refers to a decline in pleasantness of eaten foods in comparison to other non-ingested meals. Although SSS is specific to the eaten food, it can also generalize to other meals that share similar properties to the satiated food. It is possible that this phenomenon could become more specific after extensive experience, as repeated exposure to an assortment of similar food could cause perceptual learning (i.e. an increase in the distinctiveness of each specific item). This in turn would reduce generalization from the consumed food to other similar products, so they will be more readily consumed. To assess this hypothesis, two experiments were carried out using rats as experimental subjects and flavoured solutions as stimuli. In Experiment 1 our main goal was to find the basic SSS effect with two different solutions. As expected, the results showed that rats tended to consume a higher amount of non-sated solutions in comparison to sated ones. Experiment 2 evaluated how repeated exposure to two similar solutions affected generalization of the SSS. Results showed that rats that did not have extensive exposure to the flavoured solutions showed no preference for the non-sated drink. However, rats that had repeated exposure to the flavours showed SSS. The results suggest that easy and continuous access to a high variety of similar unhealthy foods might have long-term effects on food consumption, and highlight a potential mechanism linking obesogenic environments with dietary habits.

Flattening of a generalization gradient following a retention interval: Evidence for differential forgetting of stimulus features

In two experiments, rats received exposure to a compound consisting of a solution of salt plus a distinctive flavor (A), followed by an injection of furo-doca to induce a salt need. Experiment 1, established that this procedure successfully generated a preference for flavor A in a subsequent choice test between A and water. Experiment 2 used this within-event learning effect to investigate generalization, testing the rats with both A and a novel flavor (B). For different groups the interval between the training phase and the test phase was varied. Subjects tested immediately after training showed a steep generalization gradient (i.e., a strong preference for A, and a weak preference for B). Subjects given a 14-day retention interval showed a flattened gradient, a reduced level of preference for A and an enhanced preference for B. These results are interpreted in terms of changes in stimulus representations over the retention interval that act to reduce the effectiveness of the distinctive features of stimuli (the features that are necessary to ensure discrimination between them).

The Effect of Additional Exposure to the Unique Features in a Perceptual Learning Task Can Be Attributed to a Location Bias

It has been suggested that human perceptual learning could be explained in terms of a better memory encoding of the unique features during intermixed exposure. However, it is possible that a location bias could play a relevant role in explaining previous results of perceptual learning studies using complex visual stimuli. If this were the case, the only relevant feature would be the location, rather than the content, of the unique features. To further explore this possibility, we attempted to replicate the results of Lavis, Kadib, Mitchell, and Hall (2011, Experiment 2), which showed that additional exposure to the unique elements resulted in better discrimination than simple intermixed exposure. We manipulated the location of the unique elements during the additional exposure. In one experiment, they were located in the same position as that when presented together with the common element. In another experiment, the unique elements were located in the center of the screen, regardless of where they were located together with the common element. Our results showed that additional exposure only improved discrimination when the unique elements were presented in the same position as when they were presented together with the common element. The results reported here do not provide support for the explanation of the effects of additional exposure of the unique elements in terms of a better memory encoding and instead suggest an explanation in terms of location bias.