Uveal melanoma: recent advances in immunotherapy

Uveal melanoma (UM) is the most common primary intraocular cancer in adults. The incidence in Europe and the United States is 6-7 per million population per year. Although most primary UMs can be successfully treated and locally controlled by irradiation therapy or local tumor resection, up to 50% of UM patients develop metastases that usually involve the liver and are fatal within 1 year. To date, chemotherapy and targeted treatments only obtain minimal responses in patients with metastatic UM, which is still characterized by poor prognosis. No standard therapeutic approaches for its prevention or treatment have been established. The application of immunotherapy agents, such as immune checkpoint inhibitors that are effective in cutaneous melanoma, has shown limited effects in the treatment of ocular disease. This is due to UM's distinct genetics, natural history, and complex interaction with the immune system. Unlike cutaneous melanomas characterized mainly by BRAF or NRAS mutations, UMs are usually triggered by a mutation in GNAQ or GNA11. As a result, more effective immunotherapeutic approaches, such as cancer vaccines, adoptive cell transfer, and other new molecules are currently being studied. In this review, we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM

The ReadFree tool for the identification of poor readers: a validation study based on a machine learning approach in monolingual and minority-language children

: In this study, we validated the "ReadFree tool", a computerised battery of 12 visual and auditory tasks developed to identify poor readers also in minority-language children (MLC). We tested the task-specific discriminant power on 142 Italian-monolingual participants (8-13 years old) divided into monolingual poor readers (N = 37) and good readers (N = 105) according to standardised Italian reading tests. The performances at the discriminant tasks of the "ReadFree tool" were entered into a classification and regression tree (CART) model to identify monolingual poor and good readers. The set of classification rules extracted from the CART model were applied to the MLC's performance and the ensuing classification was compared to the one based on standardised Italian reading tests. According to the CART model, auditory go-no/go (regular), RAN and Entrainment100bpm were the most discriminant tasks. When compared with the clinical classification, the CART model accuracy was 86% for the monolinguals and 76% for the MLC. Executive functions and timing skills turned out to have a relevant role in reading. Results of the CART model on MLC support the idea that ad hoc standardised tasks that go beyond reading are needed

360° Ab-Interno Schlemm’s Canal Viscodilation with OMNI Viscosurgical Systems for Open-Angle Glaucoma—Midterm Results

Purpose: To evaluate the effectiveness of ab-interno microcatheterization and 360° viscodilation of Schlemm’s canal (SC) performed with OMNI viscosurgical system in open angle glaucoma (OAG) together or not with phacoemulsification. Setting: Two surgical sites. Design: Retrospective, observational. Methods: Eighty eyes from 73 patients with mild to moderate OAG underwent ab- interno SC viscodilation performed with OMNI system. Fifty eyes (Group 1) underwent only SC viscodilation, while 30 eyes (Group 2) underwent glaucoma surgery + cataract extraction. Primary success endpoint at 12 months was an intraocular pressure (IOP) reduction higher than 25% from baseline with an absolute value of 18 mmHg or lower, either on the same number or fewer ocular hypotensive medications, without further interventions. Secondary effectiveness endpoints included mean IOP, number of medications and comparison of outcomes between groups. Safety endpoints consisted of best-corrected visual acuity (BCVA), adverse events (AEs), and subsequent surgical procedures. Results: Primary success was achieved in 40.0% and 67.9% in Groups 1 and 2, respectively. Mean IOP at 12-month follow-up showed a significant reduction in both groups (from 23.0 to 15.6 mmHg, p < 0.001, and from 21.5 to 14.1, p < 0.001, in Groups 1 and 2, respectively). Mean medication number decreased in both groups (from 3.0 to 2.0, p < 0.001 and from 3.4 to 1.9, p < 0.001, in Groups 1 and 2, respectively). AEs included hyphema (2 eyes), mild hypotony (4 eyes), IOP spikes one month after surgery (1 eye). Twelve eyes (15.0%) required subsequent surgical procedures. No BCVA reduction was observed. Conclusions: Viscodilation of SC using OMNI viscosurgical systems is safe and relatively effective in reducing IOP in adult patients with OAG

Dyslexic children fail to comply with the rhythmic constraints of handwriting

In this study, we sought to demonstrate that deficits in a specific motor activity, handwriting, are associated to Developmental Dyslexia. The linguistic and writing performance of children with Developmental Dyslexia, with and without handwriting problems (dysgraphia), were compared to that of children with Typical Development. The quantitative kinematic variables of handwriting were collected by means of a digitizing tablet. The results showed that all children with Developmental Dyslexia wrote more slowly than those with Typical Development. Contrary to typically developing children, they also varied more in the time taken to write the individual letters of a word and failed to comply with the principles of isochrony and homothety. Moreover, a series of correlations was found among reading, language measures and writing measures suggesting that the two abilities may be linked. We propose that the link between handwriting and reading/language deficits is mediated by rhythm, as both reading (which is grounded on language) and handwriting are ruled by principles of rhythmic organization

The ReadFree tool for the identification of poor readers: a validation study based on a machine learning approach in monolingual and minority-language children

In this study, we validated the “ReadFree tool”: a computerized battery of 12 hierarchically organized tasks in the visual and auditory modalities, which do not imply reading. The tool has been developed to identify poor readers irrespective of their specific language background, thus, to be also suitable for Minority-Language Children (MLC). Each task's discriminant power was tested on 142 Italian-monolingual participants (8-13 years-old) that either presented a reading deficit (i.e., monolingual poor readers (mPR); N = 37) or not (i.e., monolingual good readers (mGR); N = 105). The performances at the discriminant tasks were analysed by means of a multivariate machine learning approach based on a classification and regression tree (CART) model to classify mPR versus mGR. To test the diagnostic accuracy of the ReadFree tool in MLC, we first compared reading and ReadFree tool performances in MLC (N = 68) with those in monolingual readers (mGR + mPR; N = 142). The two groups did not show any significant differences, suggesting that (i) the two samples had the same distribution of good and poor readers and (ii) the ReadFree tool can be used to test MLC without introducing any systematic bias associated with their language use experience and exposure. Secondly, the MLC’s CART classification of good and poor readers was compared to the one obtained by adopting clinical reading tests standardized on Italian monolingual children. Interestingly, the percentage of MLC evaluated as poor readers through the standardized reading tests was higher than the one produced by the ReadFree tool. This evidence supports the idea that reading tasks standardized also on MLC population are needed

RAN as a universal marker of developmental dyslexia in Italian monolingual and minority language children

Rapid Automatized Naming (RAN) is considered a universal marker of developmental dyslexia (DD) and could also be helpful to identify a reading deficit in minority-language children (MLC), in which it may be hard to disentangle whether the reading difficulties are due to a learning disorder or a lower proficiency in the language of instruction. We tested reading and rapid naming skills in monolingual Good Readers (mGR), monolingual Poor Readers (mPR), and MLC, by using our new version of RAN, the RAN-Shapes, in 127 primary school students (from 3rd to 5th grade). In line with previous research, MLC showed, on average, lower reading performances as compared to mGR. However, the two groups performed similarly to the RAN-Shapes task. On the contrary, the mPR group underperformed both in the reading and the RAN tasks. Our findings suggest that reading difficulties and RAN performance can be dissociated in MLC; consequently, the performance at the RAN-Shapes may contribute to the identification of children at risk of a reading disorder without introducing any linguistic bias, when testing MLC

The causal role of the lateral occipital complex in visual mirror symmetry detection and grouping: an fMRI-guided TMS study

Despite the fact that bilateral mirror symmetry is an important characteristic of the visual world, few studies have investigated its neural basis. Here we addressed this issue by investigating whether the object-selective lateral occipital (LO) cortex, a key brain region in object and shape processing, is causally involved in bilateral symmetry detection. Participants were asked to discriminate between symmetric and asymmetric dot patterns, while fMRI-guided repetitive TMS was delivered online over either the left LO, the right LO or two control sites in the occipital cortex. We found that the application of TMS over both right and left LO impaired symmetry judgments, with disruption being greater following right LO than left LO TMS, indicative of right hemisphere lateralization in symmetry processing. TMS over LO bilaterally also affected a visual contour detection task, with no evidence for hemispheric difference in this task. Overall, our results demonstrates that LO bilaterally plays a causal role in symmetry detection possibly due to symmetry acting as a strong cue in Gestalt processes mediating object recognition

Persistence of immunity after vaccination with a capsular group B meningococcal vaccine in 3 different toddler schedules.

BACKGROUND: One schedule for the capsular group B meningococcal vaccine 4CMenB is 2 doses that are administered 2 months apart for children aged 12-23 months, with a booster dose 12-24 months later. Our objective was to provide data on persistence of human serum bactericidal antibody (hSBA) titres in children up to 4 years of age after initial doses at 12-24 months, and immunogenicity of a booster dose at 48 months of age compared with vaccine-naive children. METHODS: Children previously immunized, as part of a randomized controlled trial, with 2 doses of 4CMenB vaccine at 12-24 months of age received a booster at 4 years of age. Vaccine-naive age-matched toddlers received 2 doses of 4CMenB. Human serum bactericidal antibody titres against reference strains H44/76, 5/99, NZ98/254 and M10713 were evaluated before and after innoculation with 4CMenB vaccine in 4-year-old children. RESULTS: Of 332 children in the study, 123 had previously received 4CMenB and 209 were vaccine-naive controls. Before the booster, the proportions of participants (previously vaccinated groups compared with controls) with hSBA titres of 1:5 or more were as follows: 9%-11% v. 1% (H44/76), 84%-100% v. 4% (5/99), 0%-18% v. 0% (NZ98/254) and 59%-60% v. 60% (M10713). After 1 dose of 4CMenB in previously immunized children, the proportions of participants achieving hSBA titres of 1:5 or more were 100% (H44/76 and 5/99), 70%-100% (NZ98/254) and 90%-100% (M10713). INTERPRETATION: We found that waning of hSBA titres by 4 years of age occurred after 2 doses of 4CMenB vaccine administered at 12-24 months, and doses at 12-24 months have a priming effect on the immune system. A booster may be necessary to maintain hSBA titres of 1:5 or more among those children with increased disease risk. Trial registration: ClinicalTrials.gov, no. NCT01717638