The european paediatric legislation: benefits and perspectives

BACKGROUND: The lack of availability of appropriate medicines for children is an extensive and well known problem. Paediatricians and Physicians who take care of the paediatric population are primarily exposed to cope with this negative situation very often as more than half of the children are prescribed off-label or unlicensed medicines.DISCUSSION: Medicinal products used to treat this population should be subjected to ethical research of high quality and be explicitly authorized for use in children as it happens in adults. For that reason, and following the US experience, the European Paediatric Regulation has been amended in January 2007 by the European Commission. The objective of the Paediatric Regulation is to improve the development of high quality and ethically researched medicines for children aged 0 to 17 years, to facilitate the availability of information on the use of medicines for children, without subjecting children to unnecessary trials, or delaying the authorization of medicines for use in adults.SUMMARY: The Paediatric Regulation is dramatically changing the regulatory environment for paediatric medicines in Europe and is fuelling an increased number of clinical trials in the paediatric population. Nevertheless, there are some risks and pitfalls that need to be anticipated and controlled in order to ensure that children will ultimately benefit from this European initiative

Visual motion integration is mediated by directional ambiguities in local motion signals

The output of primary visual cortex (V1) is a piecemeal representation of the visual scene and the response of any one cell cannot unambiguously guide sensorimotor behavior. It remains unsolved how subsequent stages of cortical processing combine (“pool”) these early visual signals into a coherent representation. We (Webb et al., 2007, 2011) have shown that responses of human observers on a pooling task employing broadband, random dot motion can be accurately predicted by decoding the maximum likelihood direction from a population of motion-sensitive neurons. Whereas Amano et al. (2009) found that the vector average velocity of arrays of narrowband, two-dimensional (2-d) plaids predicts perceived global motion. To reconcile these different results, we designed two experiments in which we used 2-d noise textures moving behind spatially distributed apertures and measured the point of subjective equality between pairs of global noise textures. Textures in the standard stimulus moved rigidly in the same direction, whereas their directions in the comparison stimulus were sampled from a set of probability distributions. Human observers judged which noise texture had a more clockwise (CW) global direction. In agreement with Amano and colleagues, observers' perceived global motion coincided with the vector average stimulus direction. To test if directional ambiguities in local motion signals governed perceived global direction, we manipulated the fidelity of the texture motion within each aperture. A proportion of the apertures contained texture that underwent rigid translation and the remainder contained dynamic (temporally uncorrelated) noise to create locally ambiguous motion. Perceived global motion matched the vector average when the majority of apertures contained rigid motion, but with increasing levels of dynamic noise shifted toward the maximum likelihood direction. A class of population decoders utilizing power-law non-linearities can accommodate this flexible pooling

Criterion-free measurement of motion transparency perception at different speeds

Transparency perception often occurs when objects within the visual scene partially occlude each other or move at the same time, at different velocities across the same spatial region. Although transparent motion perception has been extensively studied, we still do not understand how the distribution of velocities within a visual scene contribute to transparent perception. Here we use a novel psychophysical procedure to characterize the distribution of velocities in a scene that give rise to transparent motion perception. To prevent participants from adopting a subjective decision criterion when discriminating transparent motion, we used an ‘‘oddone-out,’’ three alternative forced-choice procedure. Two intervals contained the standard—a random-dotkinematogram with dot speeds or directions sampled from a uniform distribution. The other interval contained the comparison—speeds or directions sampled from a distribution with the same range as the standard, but with a notch of different widths removed. Our results suggest that transparent motion perception is driven primarily by relatively slow speeds, and does not emerge when only very fast speeds are present within a visual scene. Transparent perception of moving surfaces is modulated by stimulus-based characteristics, such as the separation between the means of the overlapping distributions or the range of speeds presented within an image. Our work illustrates the utility of using objective, forced-choice methods to reveal the mechanisms underlying motion transparency perception

Web-based platforms in support of industrial symbiosis Initiatives. A bibliometric review

The main purpose of this contribution is to depict most promising web-based solutions in terms of best configuration for symbiotic network. By examining 10 existing and functioning Wb-platforms of which only some have been previously explored in the previous literature, the paper aims at underling main contributions that platforms can provide to industrial symbiosis. Thanks to a mixed research method, the paper shows that the most promising way for enhancing Wb-platforms within industrial symbiosis framework is to consider multiple platforms for integrating the results obtained from the different platforms and for assessing multi-criteria procedures

Phenol Profiling and Nutraceutical Potential of Lycium spp. Leaf Extracts Obtained with Ultrasound and Microwave Assisted Techniques

In recent years, agricultural and industrial residues have attracted a lot of interest in the recovery of phytochemicals used in the food, pharmaceutical, and cosmetic industries. In this paper, a study on the recovery of phenol compounds from Lycium spp. leaves is presented. Ultrasound‐assisted extraction (UAE) and microwave‐assisted extraction (MAE) have been used with alcoholic and hydroalcoholic solvents. Methanolic UAE was the most successful technique for extracting phenols from Lycium leaves, and we used on leaves from L. barbarum and L. chinense cultivated in Italy. The extracts were then characterized as regards to the antioxidant properties by in vitro assays and the phenol profiling by a high performance liquid chromatography‐diode array detector (HPLC‐DAD). Chlorogenic acid and rutin were the main phenol compounds, but considerable differences have been observed between the samples of the two Lycium species. For example, cryptochlorogenic acid was found only in L. barbarum samples, while quercetin‐3‐O‐rutinoside‐7‐O‐glucoside and quercetin‐3‐O‐sophoroside‐7‐O‐rhamnoside only in L. chinense leaves. Finally, multivariate statistical analysis techniques applied to the phenol content allowed us to differentiate samples from different Lycium spp. The results of this study confirm that the extraction is a crucial step in the analytical procedure and show that Lycium leaves represent an interesting source of antioxidant compounds, with potential use in the nutraceutical field

Cerebellar Non-Invasive Brain Stimulation: A Frontier in Chronic Pain Therapy

Chronic pain poses a widespread and distressing challenge; it can be resistant to conventional therapies, often having significant side effects. Non-invasive brain stimulation (NIBS) techniques offer promising avenues for the safe and swift modulation of brain excitability. NIBS approaches for chronic pain management targeting the primary motor area have yielded variable outcomes. Recently, the cerebellum has emerged as a pivotal hub in human pain processing; however, the clinical application of cerebellar NIBS in chronic pain treatment remains limited. This review delineates the cerebellum’s role in pain modulation, recent advancements in NIBS for cerebellar activity modulation, and novel biomarkers for assessing cerebellar function in humans. Despite notable progress in NIBS techniques and cerebellar activity assessment, studies targeting cerebellar NIBS for chronic pain treatment are limited in number. Nevertheless, positive outcomes in pain alleviation have been reported with cerebellar anodal transcranial direct current stimulation. Our review underscores the potential for further integration between cerebellar NIBS and non-invasive assessments of cerebellar function to advance chronic pain treatment strategies

Restless Legs Syndrome: known knowns and known unknowns

Although restless legs syndrome (RLS) is a common neurological disorder, it remains poorly understood from both clinical and pathophysiological perspectives. RLS is classified among sleep-related movement disorders, namely, conditions characterized by simple, often stereotyped movements occurring during sleep. However, several clinical, neurophysiological and neuroimaging observations question this view. The aim of the present review is to summarize and query some of the current concepts (known knowns) and to identify open questions (known unknowns) on RLS pathophysiology. Based on several lines of evidence, we propose that RLS should be viewed as a disorder of sensorimotor interaction with a typical circadian pattern of occurrence, possibly arising from neurochemical dysfunction and abnormal excitability in different brain structures

Evolutionary History of Chromosome 20

The evolutionary history of human chromosome 20 in primates was investigated using a panel of human BAC/PAC probes spaced along the chromosome. Oligonucleotide primers derived from the sequence of each human clone were used to screen horse, cat, pig, and black lemur BAC libraries to assemble, for each species, a panel of probes mapping to chromosomal loci orthologous to the loci encompassed by the human BACs. This approach facilitated marker-order comparison aimed at defining marker arrangement in primate ancestor. To this goal, we also took advantage of the mouse and rat draft sequences. The almost perfect colinearity of chromosome 20 sequence in humans and mouse could be interpreted as evidence that their form was ancestral to primates. Contrary to this view, we found that horse, macaque, and two New World monkeys share the same marker-order arrangement from which the human and mouse forms can be derived, assuming similar but distinct inversions that fully account for the small difference in marker arrangement between humans and mouse. The evolutionary history of this chromosome unveiled also two centromere repositioning events in New World monkey species

Evolutionary genomic remodelling of the human 4q subtelomere (4q35.2)

BACKGROUND: In order to obtain insights into the functionality of the human 4q35.2 domain harbouring the facioscapulohumeral muscular dystrophy (FSHD) locus, we investigated in African apes genomic and chromatin organisations, and the nuclear topology of orthologous regions. RESULTS: A basic block consisting of short D4Z4 arrays (10–15 repeats), 4q35.2 specific sequences, and approximately 35 kb of interspersed repeats from different LINE subfamilies was repeated at least twice in the gorilla 4qter. This genomic organisation has undergone evolutionary remodelling, leading to the single representation of both the D4Z4 array and LINE block in chimpanzee, and the loss of the LINE block in humans. The genomic remodelling has had an impact on 4qter chromatin organisation, but not its interphase nuclear topology. In comparison with humans, African apes show very low or undetectable levels of FRG1 and FRG2 histone 4 acetylation and gene transcription, although histone deacetylase inhibition restores gene transcription to levels comparable with those of human cells, thus indicating that the 4qter region is capable of acquiring a more open chromatin structure. Conversely, as in humans, the 4qter region in African apes has a very peripheral nuclear localisation. CONCLUSION: The 4q subtelomere has undergone substantial genomic changes during evolution that have had an impact on chromatin condensation and the region's transcriptional regulation. Consequently, the 4qter genes in African apes and humans seem to be subjected to a different strategy of regulation in which LINE and D4Z4 sequences may play a pivotal role. However, the effect of peripheral nuclear anchoring of 4qter on these regulation mechanisms is still unclear. The observed differences in the regulation of 4qter gene expression between African apes and humans suggest that the human 4q35.2 locus has acquired a novel functional relevance